SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)
I. GENERAL INFORMATION
Device Generic Name:
Device Trade Name:
Device Procode:
Injectable Dermal Filler
Sculptra
LMH
Applicant’s Name and Address: Q-Med AB, a Galderma affiliate
Seminariegatan 21
SE-752 28 Uppsala, Sweden
Galderma Research & Development, LLC
14501 North Freeway
Fort Worth, TX 76177
Date(s) of Panel Recommendation: None
Premarket Approval Application (PMA) Number: P030050/S039
Date of FDA Notice of Approval: April 18, 2023
The original PMA (P030050) was approved on August 3, 2004 and is indicated for
restoration and/or correction of the signs of facial fat loss (lipoatrophy) in people with
human immunodeficiency virus under the product named Sculptra. The PMA supplement
for Sculptra Aesthetic (P030050/S002) was approved on July 28, 2009 in immune-
competent people as a single regimen for the correction of shallow to deep nasolabial fold
(NLF) contour deficiencies and other facial wrinkles in which deep dermal grid pattern
(cross-hatch) injection technique is appropriate.
Although Sculptra and Sculptra Aesthetic are identical in composition, both products were
initially marketed under these two distinct trade names and utilized labeling specific to
their respective indication. In PMA supplement P030050/S034, approved on November
23, 2021, Sculptra and Sculptra Aesthetic have been combined under the single product
trade name (Sculptra) and labeling has been revised to include the combined information
for both the approved lipoatrophy and aesthetic indications. P030050/S034 also included
alternative reconstitution and injection procedures along with the addition of lidocaine to
the product.
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II.
When the product name Sculptra Aesthetic is used, it is to align with the product name
stated in the supportive documentation. The SSEDs to support the indications referred to
above are available on the CDRH website and are incorporated by reference here.
The current supplement was submitted to expand the indication for Sculptra to include
correction of fine lines and wrinkles in the cheek region for use in immune-competent
subjects.
INDICATIONS FOR USE
Sculptra is indicated for correction of shallow to deep nasolabial fold contour
deficiencies and other facial wrinkles for use in immune-competent subjects.
Sculptra is indicated for correction of fine lines and wrinkles in the cheek region for use
in immune-competent subjects.
III.
Sculptra is intended for restoration and/or correction of the signs of facial fat loss
(lipoatrophy) in people with human immunodeficiency virus.
CONTRAINDICATIONS
Sculptra should not be used in any person who has hypersensitivity to any of the
components of Sculptra (see DEVICE DESCRIPTION).
Sculptra should not be used in patients with severe allergies manifested by a history of
anaphylaxis or history or presence of multiple severe allergies.
Sculptra should not be used in patients with known history of or susceptibility to keloid
formation or hypertrophic scarring.
IV.
Sculptra reconstituted with lidocaine hydrochloride (lidocaine) should not be used in
patients with a history of allergies to lidocaine or other amide type local anesthetics.
WARNINGS AND PRECAUTIONS
V.
The warnings and precautions can be found in the Sculptra Instructions for Use.
DEVICE DESCRIPTION
Sculptra is an injectable implant containing microparticles of poly-L-lactic acid (PLLA),
sodium carboxymethylcellulose (USP), non-pyrogenic mannitol (USP) and sterile water
for injection (SWFI) (USP). Sculptra is available in 367.5 mg dose vials and is to be
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 2 of 40
reconstituted prior to use by the addition of 5 mL or 8 mL SWFI (USP) to form a sterile,
non-pyrogenic suspension.
Sculptra is produced by aseptic manufacturing and is supplied as a sterile dry powder in a
clear glass vial sealed by a rubber bung covered by an aluminum ring and a plastic flip-off
cap.
Sculptra is available in packages of two vials.
VI. ALTERNATIVE PRACTICES AND PROCEDURES
There are other approved procedures in the United States for correction of NLF contour
deficiencies, correction of fine lines and wrinkles in the cheek region and other facial
wrinkles as well as for restoration and/or correction of the signs of facial fat loss
(lipoatrophy) in people with human immunodeficiency virus.
Alternative therapies for correction of NLF, lines and wrinkles in the cheek region and
other facial wrinkles include bovine collagen dermal fillers, human collagen dermal fillers,
hyaluronic acid-based dermal fillers and autologous fat transfer. Alternative therapies for
treating lipoatrophy in people with human immunodeficiency virus include fillers, implants
or surgery. Other methods for treatment of facial rhytids include injection of botulinum
toxin, topical creams, chemical peels, laser skin resurfacing, dermabrasion, and surgical
intervention. Each alternative has its own advantages and disadvantages. A patient should
fully discuss these alternatives with his/her physician to select the method that best meets
expectations and lifestyle.
VII. MARKETING HISTORY
Sculptra was initially developed by Biotech Industries S.A under the name NEW-FILL
®
and was approved for marketing and sale in the European Union in November 1999. The
name Sculptra was added in January 2004.
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Sculptra was approved by the FDA in August 2004 under P030050 for restoration and/or
correction of the signs of facial fat loss (lipoatrophy) in people with human
immunodeficiency virus (HIV). The PMA supplement (P030050/S002) for Sculptra
Aesthetic was approved on July 28, 2009 as a single regimen for the correction of shallow
to deep nasolabial fold contour deficiencies and other facial wrinkles in immunocompetent
people where deep dermal grid pattern (cross-hatch) injection technique is appropriate.
PMA supplement P030050/S034, approved on November 23, 2021 included alternative
reconstitution and injection procedures along with the addition of lidocaine to the product
and the combination of Sculptra and Sculptra Aesthetic under the single product trade
name (Sculptra) with labeling that includes combined information for both the approved
lipoatrophy and aesthetic indications.
On July 11, 2014 the Agency was informed that Q-Med AB located in Uppsala, Sweden
acquired ownership and all rights of the product from Valeant Pharmaceuticals North
America, LLC. The Agency was subsequently informed on July 22, 2014 that Galderma
Laboratories, L.P. would be the US point of contact for Q-Med AB.
The product has since been approved in multiple countries globally: Argentina, Australia,
Brazil, Canada, Chile, Colombia, EU/EFTA, Hong Kong, Israel, Lebanon, Malaysia,
Mexico, New Zealand, Philippines, Puerto Rico, Russia, South Africa, Saudi Arabia,
Singapore, South Korea, Taiwan, Turkey, UAE, UK and USA.
Sculptra has not been withdrawn from any marketplace for any reason.
VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH
Below is a list of the potential adverse effects (e.g., complications) associated with the use
of the device. For the specific adverse events that occurred in the clinical studies, please
see Section X below.
Post-marketing surveillance
The adverse events received from post-marketing surveillance (voluntary reporting and
published literature) for Sculptra in the US and other countries include:
x papules/nodules with or without inflammation or discoloration,
x lack of effect,
x swelling,
x mass formation/induration,
x pain/tenderness,
x granuloma (including ectropion)/foreign body reaction,
x visual disturbance including transient blurred vision, reduced visual acuity, increased
lacrimation, eyelid ptosis, dry eye and blindness,
x bruising/hematoma,
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x erythema,
x nerve injury including paresthesia, hypoesthesia and facial nerve paralysis,
x bacterial infections and abscess formation,
x inflammation,
x skin discoloration,
x injection site reactions including burning sensation, warmth and irritation,
x atrophy/scarring,
x pruritus,
x deformity/facial asymmetry,
x rash,
x hypersensitivity/allergic reaction and angioedema,
x dermatitis,
x bleeding,
x symptoms of reactivation of herpes infection,
x urticaria,
x vesicles/blisters/pustules,
x ischemia/necrosis,
x acne,
x device dislocation,
x telangiectasia,
x discharge,
x other dermatological events including alopecia, skin wrinkling, skin tightness, skin
dryness, skin hypertrophy and photosensitive reaction,
x non-dermatological events including headache, pyrexia, malaise, arthralgia, anxiety,
nausea, insomnia, dyspnea, fatigue, dizziness, muscular weakness or twitching,
lymphadenopathy, and depression
When required, depending on event, treatments may include massage/manipulation,
warm compress, nitroglycerine paste, corticosteroids, antibiotics, antihistamines,
NSAIDs, aspiration/drainage of the product, saline injections and surgery. Events which
did not resolve or where resolution information is not available at last contact were
reported.
Scarring, mostly a non-serious event, was reported in association with skin discoloration,
nodules, lumps, indurations, granulomas, hyperpigmentation, hypertrophic scars, and
suspicion of keloid formation. Time to onset when specified ranged from within 1 week
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to 24 months post-Sculptra injection and outcome ranged from ‘recovered’ to ‘ongoing’
at last contact.
Skin discoloration was reported as a non-serious event, typically reported in association
with lumps and nodules. It has also been reported with blanching and telangiectasias.
Time to onset when specified usually ranged from within 1 week to 12 months post-
injection. Outcome ranged from ‘recovered’ to ‘ongoing’ at last contact.
Serious adverse events have rarely been reported. The most commonly reported serious
adverse events for Sculptra with more than 5 reported events include papule/nodule,
swelling/edema, pain, granuloma, symptoms of visual disturbance, infection/abscess,
mass/induration, paresthesia and facial nerve paralysis, erythema, inflammation,
bruising/hematoma, discoloration, deformity, scaring/atrophy, hypersensitivity, pruritus,
rash, muscle disorders, ischemia/necrosis, urticaria and blisters.
Injection site nodules mostly occurred several months post-injection. Such nodules are
occasionally associated with inflammation or discoloration, with time to onset ranging
from 1-2 months to 14 months post-last injection. In some cases, the nodules were
reported to resolve spontaneously or following treatment with, e.g. intralesional
corticosteroids, others were described with a prolonged duration of up to 2 years. For
those nodules that were larger in size, occurring in difficult anatomical regions (e.g.
lower eyelid) or persisted after other treatments such as intralesional corticosteroids
failed, surgical excision of the nodules was required.
Granulomas usually occur several months after injection; in few cases onset was more
than 1-year post-injection. While events were reported as granuloma, only a few cases
were confirmed by biopsy. Treatment ranged from subcision or intralesional
corticosteroid with subsequent improvement, to surgical extraction. Of the few
granuloma cases that required hospitalization, these were associated with infraorbital use
or injection in the lip vermilion.
Vascular compromise may occur due to an inadvertent intravascular injection or as a
result of vascular compression associated with implantation of any injectable product.
This may manifest as blanching, discoloration, necrosis or ulceration at the implant site
or in the area supplied by the blood vessels affected; or rarely as ischemic events in other
organs due to embolization. Isolated rare cases of ischemic events affecting the eye
leading to visual loss, and the brain resulting in cerebral infarction, following facial
aesthetic treatments have been reported. Visual disturbances including blindness have
been reported following injection of Sculptra into the temple area, periorbital areas,
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 6 of 40
and/or cheek. Events requiring medical intervention, and events which did not resolve or
where resolution information is not available were reported.
Serious edema was reported in association with erythema, pain, and heat sensation. The
symptoms were mostly temporary, and with no significant impact on the quality of daily
life reported. Treatment included corticosteroids, antihistamines and/or anti-
inflammatories. Recovery occurred within 7-10 days without sequelae.
Serious erythema, serious pain, and serious pruritus reported with bruising and heat
sensation, were reported within 24 hours post-injection. Treatment included
corticosteroids, antihistamines and/or anti-inflammatories. Events resolved within 7-10
days post-injection without sequelae and with no significant impact on daily life.
Serious hypersensitivity reactions were reported mainly in association with facial
swelling and Quincke’s edema, with symptoms appearing from 1 day to 1-week post-
injection. Patients recovered without sequelae after treatment with intravenous
corticosteroids and antihistamines.
Serious infections such as subcutaneous abscesses, cellulitis, folliculitis, and methicillin-
resistant Staphylococcus aureus at the injection site, were reported. Time to onset of
event ranged from 1 day to 1 week. Of these cases a few required hospitalization with
administration of intravenous antibiotics. All patients recovered or were recovering at the
last contact.
IX. SUMMARY OF NONCLINICAL STUDIES
A. Laboratory studies
Because no change in product manufacture or specification is proposed in this supplement,
the biocompatibility studies previously presented in PMA P030050 and supplements
support the labeling changes described herein.
B. Biocompatibility studies
The ISO 10993 biocompatibility program for Sculptra was re-evaluated in 2016 utilizing
Sculptra batches produced under the current approved manufacturing conditions. Because
no change in product manufacture or specification is proposed in this supplement, the
biocompatibility studies previously presented in PMA P030050 and supplements support
the labeling changes described herein.
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X. SUMMARY OF PRIMARY CLINICAL STUDY
The applicant performed a clinical study to establish a reasonable assurance of safety and
effectiveness for the use of Sculptra for the correction of fine lines and wrinkles in the
cheek region. Data from this clinical study were the basis for the PMA approval decision. A
summary of the clinical study is presented below.
A. Study Design
Base study (0 to 12 months): Subjects were treated between 12 Nov 2019 and 13 Mar
2021 with subjects followed through Aug 12, 2021. Subjects may have participated in an
Extension study for up to 24 months. In the Extension study, Control Subjects were treated
and Base study Treatment subjects were followed with no further treatment. The database
for this PMA supplement reflects data collected for both the Base and Extension studies
through July 20, 2022 and included 149 subjects at 13 investigational sites in the US.
The study (43USSA1812) was a prospective, randomized, evaluator-blinded, no-
treatment controlled multicenter study to assess the effectiveness and safety of treatment
with Sculptra for correction of cheek wrinkles. One hundred forty-nine (149) subjects
with intent to undergo correction of cheek wrinkles with a Galderma Cheek Wrinkles
Scale (GCWS) At Rest score of 2 (moderate) or 3 (severe) on each side of the face were
randomized (2:1) to either treatment with Sculptra (treatment group; 97 subjects) or no
treatment (control group; 52 subjects). The treatment group received Sculptra
reconstituted with 8 mL of SWFI with the addition of 1 mL 2% lidocaine. All subjects
were offered to participate in an extension study in which treatment was administered to
the control group at Month 12. No further treatment was administered to the treatment
group in the extension. The extension study is complete. A total of 111 subjects
(39 control group subjects, 72 treatment group subjects) entered the extension study.
Subjects were treated to optimal correction at four-week intervals (+5 weeks), with a
maximum of four treatment sessions. Follow-up visits were conducted at Months 7, 9
and 12 after initial treatment.
1. Clinical Inclusion and Exclusion Criteria
Enrollment in the clinical study (43USSA1812) was limited to subjects who met
the following key inclusion criteria:
x Women or men over 21 years of age.
x Intent to undergo correction of cheek wrinkles on both sides of the face and
a Galderma Cheek Wrinkles Scale (GCWS) At Rest score of Moderate or
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Severe on each side of the face, as assessed on Day 1 by the Blinded
Evaluator and the Treating Investigator (agreement on score was not
required and the GCWS At Rest score for each side of the face did not need
to be equal; however, the difference between the two was limited to 1
grade).
Subjects were not permitted to be enrolled in the clinical study if they met any of
the following key exclusion criteria:
x Known/previous allergy or hypersensitivity to any of the Sculptra constituents.
x History of allergy or hypersensitivity to lidocaine or other amide-type
anesthetics, or topical anesthetics or nerve blocking agents.
x Previous use of any tissue augmenting therapy, contouring, or revitalization
treatment in or near the area of treatment.
o Calcium hydroxylapatite, Poly-L-Lactic acid, was prohibited.
o Collagen or hyaluronic acid may not have been use within 12 months of
enrollment.
x Previous treatment/procedure in the face in the previous 6 months that, in the
Treating Investigator’s opinion, would interfere with the study injections and/or
study assessments or exposes the study subject to undue risk by study
participation.
2. Follow-up Schedule
Base study (0 to 12 months): Qualified subjects were randomized to receive
treatment with Sculptra reconstituted with 8 mL of SWFI (Treatment Group) or no
treatment (Control Group). Subjects in the treatment group received treatment by
the Treating Investigator at Day 1. The method of injection was at the discretion
of the treating Investigator according to the study protocol. Subjects were treated
to optimal correction, which was defined as at least a one-step improvement on
the Galderma Cheek Wrinkles Scale (GCWS) At Rest and the best correction that
can be achieved as agreed by Treating Investigator and subject.
After the first treatment, there was a 12-month follow-up period with 6 in-clinic
visits after baseline/first treatment. Additional treatment was performed at one
month (+5 weeks) after the last treatment in up to four sessions if deemed necessary
to obtain optimal aesthetic result; this decision was agreed upon by the Treating
Investigator and the subject. Follow-up visits without treatment were conducted at
Months 7, 9 and 12.
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The Treatment group (investigational product) received a maximum of 2 vials (9
mL total volume per vial with 1 mL added lidocaine solution included) of Sculptra
per treatment session with a maximum of 9 mL per cheek. The Control group did
not receive any treatment. Dose amount maximums were the same for all treatment
sessions.
Subjects were contacted by telephone 72 hours after each treatment (i.e. initial,
optional touch-up, as applicable) for safety follow-up.
Subjects evaluated injection site reactions in a 28-day diary, starting on the day of
treatment and at each treatment time point.
Extension Study (12-24 months): During the extended follow-up period, control
group subjects were offered Sculptra treatment (Designated as Group A), and
treatment group subjects (Designated as Group B) returned for continued safety and
effectiveness evaluations up to 24 months.
Group A subjects received the same safety assessments after treatment as in the
Base study. Both Group A and B subjects had the same efficacy assessments as
during the Base study.
3. Clinical Endpoints
Safety
The objective of the study was to evaluate the safety of Sculptra in the
correction of cheek wrinkles.
Safety endpoints:
x Incidence, intensity, time to onset and duration of adverse events collected
throughout the study period.
x Incidence, intensity and number of days of pre-defined expected post-treatment
events collected using subject diaries for 28 days from each treatment.
x Safety assessment by a qualified staff member at all visits according to
predefined methods at baseline and at all follow-up visits for the Treatment
Group and the Control Group:
o Cheek firmness, symmetry and function (smiling and chewing)
o Device palpability (baseline assessment excluded)
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o Mass formation
o Cheek sensation
o Visual Function Assessments
Effectiveness
The primary effectiveness endpoint was evaluated based on responder rates
using the GCWS At Rest (Figure 1, Table 1), as assessed live by the Blinded
Evaluator at Month 12. A responder was defined as a subject with at least a 1-
grade improvement from baseline in both cheeks concurrently.
Table 1 Galderma Cheek Wrinkle Scale At Rest
None No lines or wrinkles.
Mild Only a few superficial lines
Moderate Many superficial lines or a few shallow wrinkles
Severe Many shallow wrinkles or a few moderate depth wrinkles.
Very severe Many moderate wrinkles or at least one deep wrinkle with or without
redundant folds.
Figure 1 Treatment Area Cheek region
Secondary effectiveness endpoints included responder rates over time up to Month 12
based on Blinded Evaluator assessment using GCWS At Rest and GCWS Dynamic,
percentage of subjects having at least “Improved” on the Global Aesthetic
Improvement Scale (GAIS) on both sides of the face combined as assessed live by the
subject and the Treating Investigator separately, change from baseline in subject
satisfaction using the Satisfaction with Cheeks FACE-Q questionnaire, subject
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satisfaction scores using a 5-point subject satisfaction questionnaire and time in hours
from treatment procedure until the earliest time the subject reported feeling
comfortable returning to social engagement, based on subject diary reporting.
Extension study (12 to 24 months):
Effectiveness endpoints evaluated for the long- term extension included responder
rate on both sides of the face as assessed by the Blinded Evaluator using GCWS
At Rest and GCWS Dynamic at Months 19, 21, and 24 as well as Satisfaction
with Cheeks FACE-Q™ questionnaire, subject satisfaction and GAIS at all visits,
and time in hours from treatment procedure until the earliest time the subject
reported feeling comfortable returning to social engagement based on subject
diary reporting.
B. Accountability of PMA Cohort
Base study (0 to 12 months): A total of 149 subjects were enrolled and randomized. A
total of 134 (89.9%) subjects completed the study (90.7% treatment group, 88.5% control
group); the most common reason for study discontinuation was subjects being lost to
follow-up (4 [4.1%] subjects in the treatment group, 2 [3.8%] subjects in the control group).
One subject discontinued the study for medical reasons.
Ninety-seven (97) subjects were treated with Sculptra reconstituted with 8 mL of SWFI
with the addition of 1 mL 2% lidocaine and a reference group of fifty-two (52) subjects
did not receive any treatment.
Table 2 Summary of Subject Disposition: All Subjects
Category
Control Group Treatment Group
n (%) n (%)
Total
n (%)
Screened 183
Screening failures 34
Intent-to-treat population
a
52 97 149
Safety population
b
52 (100) 97 (100) 149 (100)
Per-protocol population
c
45 (86.5) 86 (88.7) 131 (87.9)
Completed study, n (%) 46 (88.5) 88 (90.7) 134 (89.9)
Premature study discontinuation, n (%) 6 (11.5) 9 (9.3) 15 (10.1)
Primary reason for study discontinuation
Medical reason 0 1 (1.0) 1 (0.7)
Withdrawal of informed consent (not 2 (3.8) 1 (1.0) 3 (2.0)
due to coronavirus disease-19
concerns)
Withdrawal of informed consent (due 1 (1.9) 3 (3.1) 4 (2.7)
to coronavirus disease-19 concerns)
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Category
Control Group Treatment Group
n (%) n (%)
Total
n (%)
Lost to follow-up 2 (3.8) 4 (4.1) 6 (4.0)
Other 1 (1.9)
d
0 1 (0.7)
a All subjects who were randomized based on the as-randomized principle (i.e., according to
the treatment they were randomized to).
b All subjects who were treated with Sculptra or randomized to no treatment control group.
Subjects were analyzed based on the as-treated principle (i.e., according to the treatment they
actually received).
c All intent-to-treat subjects who completed 12 months after the baseline visit without any
deviations considered to have a substantial impact on the primary effectiveness outcome (this
was determined by the Sponsor).
d One subject was a screen failure due to previous use of Radiesse; however, they were
randomized erroneously but did not receive treatment.
Note: N = number of subjects; n = number of subjects in a specific category. Percentages
calculated as 100 × (n/N) in the intent-to-treat population.
The safety population includes all subjects who were treated with Sculptra or randomized
to the no treatment control group. Subjects were analyzed based on the as-treated principle
(i.e., according to the treatment they actually received).
The Intent-to-treat (ITT) population includes all subjects who were randomized based on
the as randomized principle (i.e., according to the treatment they were randomized to).
The per protocol (PP) population included all ITT subjects with a completed Month 12
after baseline assessment of the Blinded Evaluator GCWS At Rest and without any
deviations considered to have a substantial impact on the primary effectiveness outcome.
Extension study (12 to 24 months):
Of the 134 subjects eligible for the extension study, 111 subjects enrolled in the extension
study. The most common reason for subjects not participating in the extension study was
the requirement for follow-up visits. A total of 104 (93.7%) subjects completed the
extension study. The most common reason for study discontinuation was the subject
being lost to follow-up (5 [4.5%] subjects).
C. Study Population Demographics and Baseline Parameters
Base study (0 to 12 months): The demographics of the study are typical for a pivotal study
performed in the US for this indication. The demographics of the study population are
presented in Table 3.
The majority of subjects were female (96.6%), White (90.6%), and not Hispanic or Latino
(91.9%); the mean age was 60.7 years.
The most common Fitzpatrick Skin Type (FST) for all subjects was FST III (45.6%) and
the least common was FST VI (3.4%). This study was designed to enroll an ethnically
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diverse population by including at least fifteen subjects with FST IV and 14 subjects with
FST V-VI. There was a total of 32 FST IV-VI subjects (21.5% of all subjects; 21.6% in
treatment group and 21.2% in the control group). All subjects had a moderate or severe
GCWS at rest score on both sides of the face.
Table 3 Subject demographics and baseline characteristics
Control Group Treatment Group Total
(N=52) (N=97) (N=149)
Age (years)
n 52 97 149
Mean (SD) 60.4 (8.72) 60.9 (8.50) 60.7 (8.55)
Median 60.0 60.0 60.0
Min, Max 45, 88 41, 89 41, 89
Age Category, n (%)
>=55 years 39 (75.0) 77 (79.4) 116 (77.9)
<55 years 13 (25.0) 20 (20.6) 33 (22.1)
Gender, n (%)
Female 50 (96.2) 94 (96.9) 144 (96.6)
Male 2 (3.8) 3 (3.1) 5 (3.4)
Race, n (%)
American Indian/Alaska Native 0 1 (1.0) 1 (0.7)
Asian 1 (1.9) 1 (1.0) 2 (1.3)
Black/African American 4 (7.7) 7 (7.2) 11 (7.4)
Native Hawaiian/Other Pacific Islander 0 0 0
White 47 (90.4) 88 (90.7) 135 (90.6)
Other 0 0 0
Multiple [1] 0 0 0
Ethnicity, n (%)
Not Hispanic or Latino 47 (90.4) 90 (92.8) 137 (91.9)
Hispanic or Latino 5 (9.6) 7 (7.2) 12 (8.1)
Fitzpatrick Skin Type Score, n (%)
I 2 (3.8) 4 (4.1) 6 (4.0)
II 18 (34.6) 25 (25.8) 43 (28.9)
III 21 (40.4) 47 (48.5) 68 (45.6)
IV 6 (11.5) 12 (12.4) 18 (12.1)
V 4 (7.7) 5 (5.2) 9 (6.0)
VI 1 (1.9) 4 (4.1) 5 (3.4)
Galderma Cheek Wrinkles Scale (GCWS) – At Rest,
Blinded Evaluator, n (%)
Left
None 0 0 0
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Control Group Treatment Group Total
(N=52) (N=97) (N=149)
Mild 0 0 0
Moderate 28 (53.8) 50 (51.5) 78 (52.3)
Severe 24 (46.2) 47 (48.5) 71 (47.7)
Very Severe 0 0 0
Galderma Cheek Wrinkles Scale (GCWS) – At Rest,
Blinded Evaluator, n (%)
Right
None 0 0 0
Mild 0 0 0
Moderate 37 (71.2) 60 (61.9) 97 (65.1)
Severe 15 (28.8) 37 (38.1) 52 (34.9)
Very Severe 0 0 0
[1] 'Multiple' category includes subjects with more than one race selected on eCRF.
Note: N = Number of subjects, n = Number of subjects in specific category. Percentages calculated as 100 x (n/N). SD = Standard Deviation.
Extension Study (12 to 24 months): As subjects enrolled from the base study, the above
demographics presented is representative of the study population.
Treatment regimen
Base study (0 to 12 months): The first treatment was administered at the baseline visit.
Additional treatments were performed if deemed necessary to obtain optimal aesthetic
result one month after the last treatment in up to four treatment sessions in total. Subjects
were treated to optimal correction, which was defined as at least a 1 grade improvement on
the GCWS At Rest and best correction that could have been achieved as agreed upon by
the Treating Investigator and the subject.
Sculptra was injected using the following injection techniques; linear threading, bolus,
fanning and cross-hatching technique, in the subdermal plane; subcutaneously or
supraperiosteally. Subjects were given a maximum of two vials per session, with a
maximum of one vial per side, (i.e. maximum 9 mL per side). Overall, a total mean
injection volume of 54.11 mL was received per subject in the treatment group. The median
injection volume (left + right sides) at each treatment session was 16.00 mL. The minimum
volume injected was 7.5 mL in session 1, 8.0 mL in session 2, 3.0 mL in session 3, and 6.1
mL in session 4; the maximum volume injected at each treatment session was 18.0 mL.
The mean number of treatments was 3.6 (range 1-4).
A summary of overall treatment administration characteristics for all treatment sessions is
presented in Table 4. Subjects received a combination of injection techniques, at the
discretion of the Treating Investigator using a 25 G needle. Linear retrograde (91.3%) and
fanning (81.2%) were the most common injection techniques used. The majority of
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 15 of 40
subjects received one vial per session (96.8%). All subjects received injections in the
subcutaneous region and 67% also received injections in the supraperiosteal plane.
61.2% of the subjects received anesthetics (local), even though lidocaine was added to the
investigational product prior to injection. 83.8% of all subjects received injection
concomitant procedures (i.e., massage, ice pack, or other) at the time of treatment.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 16 of 40
Table 4 Overall treatment administration characteristics (Treatment group)
(Safety population)
Treatment Treatment Treatment Treatment
1 2 3 4 Total
(N=97) (N=95) (N=86) (N=67) (N=345)
Characteristic n (%) n (%) n (%) n (%) n (%)
Number of vials used
One 92 (94.8) 91 (95.8) 86 (100) 65 (97.0) 334 (96.8)
Two 5 (5.2) 4 (4.2) 0 2 (3.0) 11 (3.2)
Was 25-gauge needle used for
injection
Yes 97 (100) 95 (100) 86 (100) 67 (100) 345 (100)
Injection method
a
Linear antegrade 38 (39.2) 39 (41.1) 36 (41.9) 25 (37.3) 138 (40.0)
Linear retrograde 87 (89.7) 85 (89.5) 79 (91.9) 64 (95.5) 315 (91.3)
Bolus 20 (20.6) 22 (23.2) 18 (20.9) 14 (20.9) 74 (21.4)
Fanning 78 (80.4) 77 (81.1) 73 (84.9) 52 (77.6) 280 (81.2)
Cross hatching 33 (34.0) 34 (35.8) 38 (44.2) 26 (38.8) 131 (38.0)
Depth of injection, left side
Subcutaneous 97 (100) 95 (100) 86 (100) 67 (100) 345 (100)
Supraperiosteal 67 (69.1) 63 (66.3) 56 (65.1) 45 (67.2) 231 (67.0)
Depth of injection, right side
Subcutaneous 97 (100) 95 (100) 86 (100) 67 (100) 345 (100)
Supraperiosteal 67 (69.1) 63 (66.3) 56 (65.1) 45 (67.2) 231 (67.0)
Any anesthetics used before injection 62 (63.9) 61 (64.2) 53 (61.6) 35 (52.2) 211 (61.2)
Topical 56 (57.7) 55 (57.9) 49 (57.0) 31 (46.3) 191 (55.4)
Local injection 6 (6.2) 6 (6.3) 4 (4.7) 4 (6.0) 20 (5.8)
None 35 (36.1) 34 (35.8) 33 (38.4) 32 (47.8) 134 (38.8)
Any injection concomitant procedures 79 (81.4) 81 (85.3) 74 (86.0) 55 (82.1) 289 (83.8)
Massage 60 (61.9) 64 (67.4) 60 (69.8) 42 (62.7) 226 (65.5)
Ice pack 61 (62.9) 59 (62.1) 51 (59.3) 37 (55.2) 208 (60.3)
Other 6 (6.2) 6 (6.3) 6 (7.0) 5 (7.5) 23 (6.7)
None 18 (18.6) 14 (14.7) 12 (14.0) 12 (17.9) 56 (16.2)
Any technical problems 0 1 (1.1) 1 (1.2) 0 2 (0.6)
a Injector was to check all that applied.
Note: N = number of treatments given to subjects in safety population, n = number of
treatments given for specific category. Percentages calculated as 100
× (n/N).
Extension study (12 to 24 months):
Only Group A subjects received treatment with Sculptra in the Extension study and
followed the same treatment schedule as the Base study. Overall, similar injection volumes
were seen in the Extension study.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 17 of 40
Overall, a total mean injection volume of 62.84 mL was received per subject in Group A.
The median injection volume (left + right sides) at each treatment ranged from 16.50 to
16.80 mL. The minimum volume injected was 8.5 mL at treatment 4 and 9.0 mL at
treatments 1, 2, and 3; the maximum volume injected at each treatment was 18.0 mL.
D. Safety and Effectiveness Results
1. Safety Results
Base study (0 to 12 months): The analysis of safety was based on all 149 subjects
included in the study. The key safety outcomes for this study are presented below in
Tables 5 – 9. Subject reported injection related events are presented in Table 5 and Table
6. Adverse events (AEs) are presented in Table 7, Table 8 and Table 9.
Pre-defined Injection Related Events:
Base study (0 to 12 months): Pre-printed diary forms were used by subjects to record the
presence of pre-defined expected post-treatment events in the treated area, i.e. bruising,
redness, swelling, pain, tenderness, itching, lumps/bumps, and “other” for 28 days
following each treatment. Subjects rated each treatment site response as “None”, “Mild”,
“Moderate” or “Severe”.
Overall, for either side of the face, 92 (98.9%) subjects in the treatment group reported
symptoms. The most common symptoms overall were tenderness (93.5%), bruising
(93.5%), swelling (87.1%), and pain (including burning) (83.9%). Overall, almost all
symptoms were mild or moderate in intensity (97.8%) and the majority resolved within
14 days (76.1%).
Device and Injection Related Events:
Adverse events (AEs) were evaluated by Investigators throughout entirety of the study. In
addition, Vision function assessments: Snellen Visual Acuity Test, Extraocular Muscle
Function Test and Confrontation Visual Field Test, was performed both prior to and post
injection of the study product at baseline, before and after treatments, and all physical
scheduled follow-up visits. At all physical visits, a study staff member who was qualified
by training and experience to perform safety assessments assessed each subject’s cheek
sensation; firmness and symmetry; and mass formation. After treatment with the study
product, product palpability was performed at each physical visit.
No clinically meaningful changes from baseline in visual function assessments or
functionality, sensation, cheek firmness and symmetry, mass formation, or abnormal
device palpability were observed.
One subject experienced a unilateral 1-line change in the Snellen Visual Acuity test from
Baseline at Month 1 post injection (0+, -1), but reported no ocular symptoms or vision loss.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 18 of 40
All other eye and safety assessments were normal throughout the completion of the Month
1 visit for the subject. Subject did not return for additional assessments.
Three subjects in the control group experienced a change in Snellen Visual Acuity test from
baseline to a post-baseline visit. These occurrences are due to the subjects not wearing their
corrective lenses for the post-baseline assessments.
An overview of adverse events is presented below in Table 7. An overall summary of
AEs following treatment is presented in Tables 8 and 9. Out of the 97 subjects
randomized to treatment, a total of 20 subjects (20.6%) experienced an AE considered
related to study treatment. The most common (>1.0% of subjects in the treatment group)
related AEs were injection site bruising (11 [11.3%] subjects), dizziness (2 [2.1%]
subjects), and headache (2 [2.1%]) subjects.
All AEs related to study product or injection procedure reported in the treatment group
were mild or moderate in intensity. Three (3.1%) subjects experienced related AEs of
moderate intensity (one experienced 2 events of moderate injection site pain, one subject
experienced moderate dizziness, and one subject experienced moderate injection site
bruising) and all events resolved by the end of the study.
One (1.0%) subject in the treatment group experienced an adverse event of special
interest (AESI), an AE of hypermetropia with late onset (>21 days after the most recent
treatment) related to study product or injection procedure, mild in intensity. The duration
of the event was 37 days and was resolved without action taken.
One subject experienced multiple small, palpable skin nodules in the treatment area on
both her left and right cheeks (PT: injection site nodule) on Day 332, 180 days after her
most recent injection The AEs (for both the left and right cheeks) were considered mild
in intensity and were ongoing at study completion. No action was taken with regard to the
AEs.
One subject experienced a 5-6 mm small, oblong lump that was palpable on her lower left
cheek, near the corner of their mouth (PT: skin mass [small lump]) on Day 49, 9 days
after her most recent injection. The AE was considered mild in intensity, related to study
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 19 of 40
product and injection procedure, and resolved on Day 327 (was considered chronic
and/or stable). No action was taken with regard to the AE.
A summary of the duration (days) of AEs related to study product or injection procedure
is provided in Table 9.
Three subjects in the treatment group experienced serious adverse event (SAE)s. None of
these were considered related to study product or injection procedure.
One subject had an AE leading to study discontinuation (which was also considered an
SAE unrelated to treatment (adenocarcinoma)). No subject died during the study.
21.3% (20/94) of females experienced a related adverse event, while no male subjects
(0/5) had a related adverse event. Due to the small number of male subjects, conclusions
cannot be drawn.
Device Deficiencies
A total of 2 product complaints in a total of 650 vials were reported during the study from
2 sites. One complaint was in regard to a chipped vial being noticed during reconstitution
(which was placed in quarantine) and the other complaint stated that there was more foam
and less opacity to the study product when compared to the visual 48-hour reconstitution.
There were no AEs reported due to these deficiencies.
Table 5 Frequency and intensity of pre-defined events reported in the daily
diary
Note: N = Number of subjects in Safety Population, n = Number of subjects in specific category. For 'Any'
column, percentages calculated as 100 x (n/number of subjects with response indicating symptom or none at
applicable treatment session). For intensity columns, percentages calculated as 100 x (n/number of subjects at
treatment session with that symptom). Subjects reporting multiple events of the same symptom are counted
once for that event within the most severe category.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 20 of 40
Table 6 Frequency and duration of pre-defined events reported in the daily
diary
Note: N = Number of subjects in Safety Population, n = Number of subjects in specific category. Percentages
calculated as 100 x (n/number of subjects who reported 'Mild' or higher for the respective symptom in their
subject diary).
Table 7 Adverse Event Overview
Control Group Treatment Group
(N=52) (N=97)
Subjects with at least 1: n (%) n (%)
Adverse event 3 (5.8) 43 (44.3)
Serious adverse event 0 3 (3.1)
Adverse event leading to study discontinuation 0 1 (1.0)
Adverse event related to study product or injection 0 20 (20.6)
procedure
Adverse event unrelated to study product or injection 3 (5.8) 30 (30.9)
procedure
Serious adverse event unrelated to study product or 0 3 (3.1)
injection procedure
Adverse event of special interest 0 1 (1.0)
Adverse event with late onset (>21 days after most 0 1 (1.0)
recent treatment) related to study product or injection
procedure
No adverse event 49 (94.2) 54 (55.7)
Note: N = number of subjects, n = number of subjects in specific category. Percentages
calculated as 100 × (n/N). Subjects reporting more than 1 event in a category were counted
only once in that category (n); multiple events in a similar category were instead counted for
each occurrence.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 21 of 40
Table 8 Related Adverse Events by preferred term (Safety population)
Treatment Group
(N=97)
Preferred Term n (%)
Subjects with at least 1 related adverse event 20 (20.6)
Injection site bruising 11 (11.3)
Dizziness 2 (2.1)
Headache 2 (2.1)
Abnormal sensation in eye 1 (1.0)
Injection site erythema 1 (1.0)
Injection site irritation 1 (1.0)
Injection site nodule 1 (1.0)
Injection site pain 1 (1.0)
Injection site discolouration 1 (1.0)
Injection site swelling 1 (1.0)
Skin mass (small lump)
a
1 (1.0)
a One subject experienced 2 events of skin mass on Day 49, 9 days after the most recent
injection; reported terms were small lump on lower left cheek, near corner of mouth
and small lump below left corner of mouth. The AE was considered mild in intensity,
related to study product and injection procedure. These were considered chronic and
stable (not resolved) at the end of study participation but did resolve without medical
intervention after the subject exited the study per report from the Investigator.
Note: N = number of subjects in safety population, n = number of subjects in specific
category. Percentages calculated as 100 × (n/N). Subjects reporting more than 1 event
in a category were counted only once in that category (n). Events were coded by
Medical Dictionary for Regulatory Activities version 23.1.
Table 9 Related Adverse Events by Duration
System Organ Class
Preferred Term
Treatment Group
(N=97)
Abnormal sensation in eye
Mean (SD)
Median
Min, Max
Injection site bruising
Mean (SD)
Median
Min, Max
Injection site discolouration
Mean (SD)
Median
Min, Max
Injection site erythema
Mean (SD)
1
3.0 (-)
3.0
3, 3
11
11.4 (5.77)
9.0
6, 22
1
4.0 (-)
4.0
4, 4
1
13.0 (-)
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 22 of 40
System Organ Class Treatment Group
Preferred Term (N=97)
Median 13.0
Min, Max 13, 13
Injection site irritation 1
Median 3.0
Min, Max 3, 3
Injection site nodule 1
Mean (SD) 1.0 (-)
Min, Max 1, 1
Injection site pain 1
Mean (SD) 1.0 (-)
Median 1.0
Injection site swelling 1
Mean (SD) 11.0 (-)
Median 11.0
Min, Max 11, 11
Dizziness 2
Mean (SD) 1.0 (0.00)
Median 1.0
Min, Max 1, 1
Mean (SD) 1.0 (0.00)
Median 1.0
Min, Max 1, 1
Skin mass 1
Median 279.0
Min, Max 279, 279
Events are coded by MedDRA version 23.1.
Note: For 3 related events (2 subjects) ongoing at end of study, stop date is censored at the later of last vi
sit date or end of study date. Duration is derived as: stop date minus start date + 1.
Subjects reporting more than one event in a category are counted only once in that category at longest dur
ation.
Extension study (12-24 months)
During the extension study, a total of 9 (23.1%) subjects in Group A experienced an AE
considered related to study product or injection procedure. No subject in Group A
experienced an AE with late onset (>21 days after the most recent treatment), an AESI, or
an AE leading to study discontinuation.
During the extension study, no new related AEs were reported in Group B. One subject
(1.4%) experienced an AE with late onset (>21 days after the most recent treatment)
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 23 of 40
related to study product or injection procedure in the base study was which ongoing when
enrolled in the extension study. The subject withdrew prior to the AE resolving. No
subject in Group B experienced an AESI or an AE leading to study discontinuation.
No subjects in the extension study experienced an SAE considered related to study
product or procedure.
A summary of related AEs is presented in Table 10.
TABLE 10 RELATED ADVERSE EVENTS BY PREFERRED TERM
(EXTENSION POPULATION)
Preferred Term
Group A
(N=39)
n (%)
Group B
(N=72)
n (%)
Subjects with at least 1 related adverse event 9 (23.1) 1 (1.4)
Injection site bruising 5 (12.8) 0
Injection site pain 2 (5.1) 0
Injection site pruritus 1 (2.6) 0
Injection site swelling 1 (2.6) 0
Injection site nodule 0 1 (1.4)
Sinusitis 1 (2.6) 0
Source: CSR, Table 14.3.2.1
Note: N = number of subjects in extension population, n = number of subjects in specific category. Percentages
calculated as 100 × (n/N). Subjects reporting more than 1 event in a category were counted only once in that
category (n). Events were coded by Medical Dictionary for Regulatory Activities version 23.1. Group A
subjects were untreated in the Base study but received Sculptra Aesthetic in the Extension study; Group B
subjects received Sculptra Aesthetic in the Base study but were untreated in this extension study.
Subject diaries captured self-assessed, pre-defined, expected, post-treatment symptoms.
The most common symptoms for Group A were tenderness, swelling, bruising, pain
(including burning), and redness. Almost all symptoms were mild or moderate in intensity
(94.9%).
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 24 of 40
TABLE 11
SUMMARY OF SUBJECT DIARY SYMPTOMS, OVERALL (GROUP A)
(EXTENSION POPULATION)
Characteristic
Group A
(N=39)
n (%)
Number of subjects with diaries at visit
Overall, Any Symptom 39 (100)
Pain (including burning) 32 (82.1)
Tenderness 37 (94.9)
Redness 32 (82.1)
Bruising 36 (92.3)
Swelling 37 (94.9)
Itching 15 (38.5)
Lumps/bumps 26 (66.7)
Source: CSR,Table 14.3.8.1
Note: N = number of subjects in extension population; n = number of subjects in specific category. Percentages
calculated as 100 × (n/number of subjects with response indicating symptom or none at applicable treatment
session). Subjects reporting multiple events of the same symptom were counted only once for that event within
the most severe category. Group A subjects were untreated in the Base study but received Sculptra Aesthetic in
the Extension study.
Snellen visual acuity assessment had no subjects in Group A with a change from any
treatment visit pre-injection to any treatment visit (post-injection). Only 1 subject (2.6%)
in Group A had a visual acuity line change at any follow-up visit. The one subject KDG
visual acuity line change at Month 13 (pre-injection), but was normal at the post-injection
visit at Month 13 and throughout the rest of the study.
2. Effectiveness Results
Base study (0 to 48 weeks): The analysis of effectiveness was based on the ITT
population of 149 subjects with data available up to the Month 12 evaluation. Three
(2.0%) subjects (2 [2.1%] subjects in the treatment group and 1 [1.9%] subject in the
control group) experienced protocol deviations that resulted in their exclusion from the
PP population. Both subjects in the treatment group experienced an out-of-window visit
and the 1 subject in the control group received a prohibited medication or procedure. The
primary effectiveness endpoint was the responder rate based on the GCWS At Rest, as
assessed live by the Blinded Evaluator, at Month 12. A responder was defined as a
subject with at least a 1-grade improvement from baseline in both cheeks concurrently.
As shown in Table 12, there was a statistically significantly higher responder rate based
on the GCWS At Rest (Blinded Evaluator) at Month 12 for the treatment group compared
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 25 of 40
with the control group (70.7% versus 25.9%, respectively; p<.0001). Similar results were
observed for the PP population using observed cases analysis.
Table 12 Responder Rate Based on the GCWS At Rest (Blinded Evaluator) at Month
12 (Multiple Imputation Analysis - Intent to Treat Population)
Treatment
Statistic Control Group Group
Observed cases responder rate, n/N (%)
a
12/46 (26.1) 63/88 (71.6)
Estimated responder rate
b
25.9 70.7
95% confidence interval
c
13.4, 38.3 61.1, 80.4
P-value
d
Mean
e
<.0001
Maximum
e
<.0001
Difference 95% confidence interval
c,f
29.4, 60.3
GCWS = Galderma Cheek Wrinkles Scale
a Defined as at least a 1-grade improvement from baseline on both sides of the face concurrently.
b Estimated with 10 imputation datasets and full conditionals, which included the assigned treatment, side of
face, and all GCWS up to Month 12 (inclusive).
c Confidence interval calculated using multiple imputation methods.
d Two-sided p-value as calculated via Fisher’s exact test.
e Across 10 imputation data sets.
f Difference confidence interval calculated using normal approximation.
Note: N = number of subjects; n = number of subjects in specific category. Percentages calculated as 100
× (n/N) out of the number of subjects at each visit. Ten datasets were multiply imputed; only subjects with
a baseline score were included. One subject (control group) who did not have a baseline value was
excluded from analysis. Fourteen subjects (5 control group, 9 treatment group) had Month 12 scores
imputed.
Primary Endpoint: The primary effectiveness endpoint was the responder rate based on
the GCWS At Rest, as assessed live by the Blinded Evaluator, at Month 12. A responder
was defined as a subject with at least a 1-grade improvement from baseline in both cheeks
concurrently. As shown in Table 12, there was a statistically significantly higher responder
rate based on the GCWS At Rest (Blinded Evaluator) at Month 12 for the treatment group
compared with the control group (70.7% versus 25.9%, respectively; p<.0001). Similar
results were observed for the PP population using observed cases analysis.
.
Females reported a responder rate of 72.9% (62/85) compared to males that reported
33.3% (1/3). Due to the small number of male subjects, conclusions cannot be drawn.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 26 of 40
Secondary Effectiveness Analyses
The following secondary endpoints were evaluated to assess secondary effectiveness.
Blinded Evaluator Responder Rate, Over Time
Responder rates, defined as a subject with at least a 1-grade improvement from baseline in
both cheeks concurrently, over time based on Blinded Evaluator assessment, displayed in
Table 13, demonstrate there was a statistically significantly higher responder rate for the
treatment group compared with the control group based on the GCWS At Rest
(Blinded Evaluator) also at Months 7 (66.2% versus 38.6%, respectively; p = 0.0043) and
9 (70.6% versus 31.1%, respectively; p<.0001).
Table 13 Responder Rate based on GCWS At Rest (Blinded Evaluator) by visit
(Observed cases analysis - ITT population)
Statistic Control Group Treatment Group
Month 7 responder rate, n/N (%)
a
17/44 (38.6) 51/77 (66.2)
95% confidence interval
b
24.4, 54.5 54.6, 76.6
P-value
c
0.0043
Difference 95% confidence interval
d
9.7, 45.4
Month 9 responder rate, n/N (%)
a
14/45 (31.1) 60/85 (70.6)
95% confidence interval
b
18.2, 46.6 59.7, 80.0
P-value
c
<.0001
Difference 95% confidence interval
d
22.8, 56.1
Month 12 responder rate, n/N (%)
a
12/46 (26.1) 63/88 (71.6)
95% confidence interval
b
14.3, 41.1 61.0, 80.7
P-value
c
<.0001
Difference 95% confidence interval
d
29.7, 61.3
GCWS = Galderma Cheek Wrinkles Scale
a Defined as at least a 1-grade improvement from baseline on both sides of the face concurrently.
b Confidence interval calculated using Clopper-Pearson method (based on binomial distribution).
c Two-sided p-value as calculated via Fisher’s exact test.
d Difference confidence interval calculated using normal approximation.
Note: N = number of subjects; n = number of subjects in specific category. Percentages
calculated as 100 × (n/N) out of the number of subjects at each visit.
GCWS Dynamic. As displayed in Table 14, there was a statistically significantly higher
responder rate for the treatment group compared with the control group based on the
GCWS Dynamic (Blinded Evaluator) at Months 7 (67.5% versus 27.3%, respectively;
p<.0001), 9 (64.7% versus 22.2%, respectively; p<.0001), and 12 (70.5% versus 28.3%,
respectively; p<.0001).
Table 14 Responder Rate based on the GCWS Dynamic (Blinded Evaluator) by visit
(Observed cases analysis - ITT population)
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 27 of 40
Statistic Control Group Treatment Group
Month 7 responder rate, n/N (%)
a
12/44 (27.3) 52/77 (67.5)
95% confidence interval
b
15.0, 42.8 55.9, 77.8
P-value
c
<.0001
Difference 95% confidence interval
d
23.5, 57.1
Month 9 responder rate, n/N (%)
a
10/45 (22.2) 55/85 (64.7)
95% confidence interval
b
11.2, 37.1 53.6, 74.8
P-value
c
<.0001
Difference 95% confidence interval
d
26.6, 58.3
Month 12 responder rate, n/N (%)
a
13/46 (28.3) 62/88 (70.5)
95% confidence interval
b
16.0, 43.5 59.8, 79.7
P-value
c
<.0001
Difference 95% confidence interval
d
26.1, 58.3
a Defined as at least a 1-grade improvement from baseline on both sides of the face concurrently.
b Confidence interval calculated using Clopper-Pearson method (based on binomial distribution).
c Two-sided p-value as calculated via Fisher’s exact test.
d Difference confidence interval calculated using normal approximation.
Note: N = number of subjects; n = number of subjects in specific category. Percentages
calculated as 100 × (n/N) out of the number of subjects at each visit.
Independent Photographic Review
Improvement rate based on the Independent Photographic Reviewer’s (IPR) assessment
using random pairings of 2D-photographs from baseline and Month 12 were conducted at
study completion. An improved subject was defined as a subject for whom the IPR
correctly identified the Month 12 photograph in the pair of pre- and post-treatment
photographs at rest
1
. The responder rate was 37% in the treatment group and 16% in the
no treatment group. The IPR responder rates are expected to be lower due to the
challenges and limitations of evaluating changes in wrinkle severity on 2D-photography.
Subject and Treating Investigator Global Aesthetic Improvement Scale (GAIS)
As shown in Table 15, the percentage of responders (as assessed by the GAIS - Treating
Investigator) ranged from 68.1% to 96.3% across Month 1 through Month 12 for the
treatment group and from 4.3% to 6.8% across Month 7 through Month 12 for the control
group. Excluding Month 1, CIs were >80% for the treatment group from Month 2 through
Month 12.
1
Note: The definition of responder for the control group was changed to match the same definition for the
treatment group.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 28 of 40
Table 15 GAIS Improvement Rates by Treating Investigator by visit
(ITT population)
Time Point Control Group Treatment Group
Month 1 responder: any improvement, n/N (%)
a
64/94 (68.1)
95% confidence interval
b
57.7, 77.3
Month 2 responder: any improvement, n/N (%)
a
78/87 (89.7)
95% confidence interval
b
81.3, 95.2
Month 3 responder: any improvement, n/N (%)
a
78/81 (96.3)
95% confidence interval
b
89.6, 99.2
Month 7 responder: any improvement, n/N (%)
a
3/44 (6.8) 74/77 (96.1)
95% confidence interval
b
1.4, 18.7 89.0, 99.2
Month 9 responder: any improvement, n/N (%)
a
2/45 (4.4) 79/85 (92.9)
95% confidence interval
b
0.5, 15.2 85.3, 97.4
Month 12 responder: any improvement, n/N (%)
a
2/46 (4.3) 83/88 (94.3)
95% confidence interval
b
0.5, 14.8 87.2, 98.1
a A responder was defined as a subject that had “very much improved”, “much improved”, or
“improved” on both sides of the face.
b Confidence interval calculated using Clopper-Pearson method (based on binomial distribution).
Note: N = number of subjects; n = number of subjects in specific category. Percentages calculated as
100 × (n/N) out of the number of subjects at each visit. Global Aesthetic Improvement Scale was first
assessed in the control group at Month 7.
Aesthetic improvement compared to baseline, as evaluated by subject assessment
(GAIS), is also summarized in Table 16. The percentage of responders ranged from
57.4% to 93.5% across Month 1 through Month 12 for the treatment group and from
6.5% to 7.0% across Month 7 to Month 12 for the control group. Excluding Months 1
and 2, CIs were >80% for the treatment group from Month 3 through Month 12.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 29 of 40
Table 16 GAIS Improvement Rates by Subject by visit
(ITT population)
Time Point Control Group Treatment Group
Month 1 responder: any improvement, n/N (%)
a
54/94 (57.4)
95% confidence interval
b
46.8, 67.6
Month 2 responder: any improvement, n/N (%)
a
69/87 (79.3)
95% confidence interval
b
69.3, 87.3
Month 3 responder: any improvement, n/N (%)
a
72/81 (88.9)
95% confidence interval
b
80.0, 94.8
Month 7 responder: any improvement, n/N (%)
a
3/43 (7.0) 72/77 (93.5)
95% confidence interval
b
1.5, 19.1 85.5, 97.9
Month 9 responder: any improvement, n/N (%)
a
3/44 (6.8) 76/85 (89.4)
95% confidence interval
b
1.4, 18.7 80.9, 95.0
Month 12 responder: any improvement, n/N (%)
a
3/46 (6.5) 81/88 (92.0)
95% confidence interval
b
1.4, 17.9 84.3, 96.7
a A responder was defined as a subject that had “very much improved”, “much improved”, or
“improved” on both sides of the face.
b Confidence interval calculated using Clopper-Pearson method (based on binomial distribution).
Note: N = number of subjects; n = number of subjects in specific category. Percentages
calculated as 100 × (n/N) out of the number of subjects at each visit. Global Aesthetic
Improvement Scale was first assessed in the control group at Month 7.
FACE-Q
™
The FACE-Q
™
scores were used to assess treatment outcome from the subject’s
perspective. FACE-Q change from baseline scores indicate subjects were more satisfied
with the appearance of their cheeks following treatment. A summary of the change from
baseline in Satisfaction with Cheeks FACE Q™ Questionnaire Rasch-transformed scores
over time is presented in Table 17. The mean score at baseline (prior to treatment) was
35.2 and 33.9 for the treatment and control groups, respectively. Based on the Rasch
transformed scores, subjects were more satisfied with how their cheeks looked following
treatment at all post-baseline visits from Month 1 through Month 12 (mean increase from
baseline range: 21.3 to 40.0), whereas subjects in the control group were not more
satisfied with how their cheeks looked at all post-baseline visits from Month 7 through
Month 12 (mean decrease from baseline range: -3.6 to -4.1).
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 30 of 40
Table 17 Satisfaction with cheeks FACE-Q™ questionnaire: Rasch-transformed
scores in subject satisfaction over time (ITT Population)
Control Group
(N=52)
Treatment Group
(N=97)
Visit Statistic Score
Change from
Baseline
Score
Change from
Baseline
Baseline n 50 97
Mean (standard deviation)
Median
33.9 (13.62)
35.0
--
--
35.2 (19.16)
35.0
--
--
Minimum, maximum 0, 63 -- 0, 100 --
Month 1 n 94 94
Mean (standard deviation)
Median
--
--
--
--
56.3 (23.73)
63.0
21.3 (24.25)
20.0
Minimum, maximum -- -- 0, 100 -35, 80
95% confidence interval -- -- -- 16.4, 26.3
Month 2 n 87 87
Mean (standard deviation)
Median
--
--
--
--
65.9 (25.50)
63.0
31.6 (28.45)
35.0
Minimum, maximum -- -- 0, 100 -44, 87
95% confidence interval -- -- -- 25.6, 37.7
Month 3 n 81 81
Mean (standard deviation)
Median
--
--
--
--
73.3 (22.41)
77.0
38.6 (26.51)
45.0
Minimum, maximum -- -- 13, 100 -78, 78
95% confidence interval -- -- -- 32.8, 44.5
Month 7 n 43 42 77 77
Mean (standard deviation)
Median
30.6 (20.17)
35.0
-4.1 (20.34)
-2.0
74.0 (23.03)
70.0
38.6 (26.30)
38.0
Minimum, maximum 0, 63 -40, 50 0, 100 -40, 87
95% confidence interval -- -10.5, 2.2 -- 32.7, 44.6
Month 9 n 45 44 85 85
Mean (standard deviation)
Median
30.2 (19.10)
35.0
-3.6 (21.36)
0.0
73.4 (23.48)
77.0
37.9 (26.63)
38.0
Minimum, maximum 0, 63 -40, 40 0, 100 -28, 87
95% confidence interval -- -10.1, 2.9 -- 32.2, 43.6
Month 12 n 46 45 88 88
Mean (standard deviation)
Median
30.6 (20.64)
35.0
-3.6 (21.76)
-5.0
75.6 (24.36)
77.0
40.0 (29.07)
46.0
Minimum, maximum
0, 91 -40, 47 0, 100 -44, 87
95% confidence interval -- -10.1, 3.0 -- 33.8, 46.1
Note: N = number of subjects; n = number of subjects in specific category. Confidence interval calculated via
t-distribution.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 31 of 40
Subject Satisfaction Questionnaire
A summary of subject satisfaction questionnaire results over time is provided below.
Across Month 7 to Month 12, the percentages of subjects in the treatment group who
responded with “very good” or “excellent” for the following questions were as follows:
x Made them look younger (48.1% to 52.9%)
x Made them feel better about themselves (49.4% to 54.1%)
x Improved their self-confidence (46.6% to 50.6%)
x Improved overall satisfaction with their appearance (46.6% to 55.3%)
x Made them look/feel more confident in their life (45.5% to 50.6%)
x Made them look the way they felt (44.3% to 50.6%)
x Improved their skin firmness (52.3% to 60.0%)
x Improved their skin radiance (51.1% to 57.6%)
x Improved their skin sagging (40.9% to 49.4%)
x Made their skin look more refreshed (50.0% to 57.6%)
Across Month 7 to Month 12, the majority of subjects in the treatment group responded as
“agree” or “strongly agree” that:
x The treatment results were natural looking (85.9% to 93.5%)
x The subtle treatment results over time were worth it (80.0% to 81.8%)
Across Month 7 to Month 12, the majority of subjects in the treatment group would
recommend the treatment to a friend (range: 88.6% to 89.6%).
Across Month 7 to Month 12, the majority of subjects in the treatment group would choose
to receive the treatment again (range: 84.4% to 89.4%).
Time to Return to Social Engagement
Based on subject diaries, the median time to feeling comfortable returning to social
engagement across the 4 treatment sessions ranged from 3.9 hours (treatment 1) to 7.1
hours (treatment 4). Overall, across all treatment sessions, 90% of subjects felt
comfortable returning to social engagement by 7.1 hours post-treatment. The remaining
10% did not complete the return to social engagement assessment. There were no
subjects with missing or incomplete data from the subject diary that reported related
adverse events associated with social circumstances or social avoidant behavior.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 32 of 40
3. Subgroup Analyses
The primary effectiveness analysis was repeated in subgroups defined by age group (<55
\HDUV55 years) and FST group (I-III, IV-VI). The responder rate was higher for subjects
<55 \HDUVRIDJH FRPSDUHGZLWKVXEMHFWV years of age (67.1%) in the treatment
group; however, the responder rate was higher in the treatment group compared with the
control group for both younger (<55 \HDUVRIDJH DQGROGHU \HDUVRIDJHVXEMHFWV
The responder rate was higher for subjects with FST IV-VI (87.5%) compared with
subjects with FST I-III (68.1%) in the treatment group; however, the responder rate was
higher in the treatment group compared with the control group for both subjects with FST
I-III and subjects with FST IV-VI. Regardless of age group or FST group, the responder
rate was higher in the treatment group versus the control group for all subgroups.
Extension study (12 to 24 months):
GCWS data showed that the effects of Sculptra treatments were maintained through 24
months as displayed in Table 18 below.
TABLE 18
RESPONDER RATE BASED ON THE GCWS AT REST (BLINDED
EVALUATOR) BY VISIT (OBSERVED CASES ANALYSIS - EXTENSION
POPULATION)
Statistic Group B
Month 19 responder rate, n/N (%)
1
56/66 (84.8)
95% confidence interval
2
73.9, 92.5
Month 21 responder rate, n/N (%)
1
50/65 (76.9)
95% confidence interval
2
64.8, 86.5
Month 24 responder rate, n/N (%)
1
50/65 (76.9)
95% confidence interval
2
64.8, 86.5
Source: CSR, Table 14.2.1.1
GCWS = Galderma Cheek Wrinkles Scale
1 Defined as at least a 1-grade improvement from pre-treatment on both sides of the face concurrently.
2 Confidence interval calculated using Clopper-Pearson method (based on binomial distribution).
Note: N = Number of subjects, n = Number of subjects in specific category. Percentages calculated as 100
x (n/N) out of the number of subjects at each visit. Group B subjects received Sculptra Aesthetic in Study
43USSA1812 but were untreated in this extension study.
The percentage of responders (as assessed by the GAIS - Treating Investigator), ranged
from 93.8% to 97.0% across Month 19 (first assessment time point) through Month 24 for
Group B, with CIs >80% for Group B from Month 19 through Month 24. The percentage
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 33 of 40
of responders (as assessed by the GAIS – subject assessment), ranged from 86.2% to 93.8%
across Month 19 through Month 24 for Group B, with CIs >80% for Group B at Month 21.
In general, subjects remained satisfied with the treatment throughout this extension study.
The treated control subjects reported similar improvements in GAIS. The results are
displayed in Table 19.
TABLE 19
GLOBAL AESTHETIC IMPROVEMENT SCALE IMPROVEMENT RATES BY
TREATING INVESTIGATOR AND BY SUBJECT BY VISIT
(EXTENSION POPULATION)
By treating investigator By subject
Time Point Group B Group B
Month 19 responder: any improvement, n/N (%)
1
64/66 (97.0) 58/67 (86.6)
95% confidence interval
2
89.5, 99.6 76.0, 93.7
Month 21 responder: any improvement, n/N (%)
1
63/65 (96.9) 61/65 (93.8)
95% confidence interval
2
89.3, 99.6 85.0, 98.3
Month 24 responder: any improvement, n/N (%)
1
61/65 (93.8) 56/65 (86.2)
95% confidence interval
2
85.0, 98.3 75.3, 93.5
Source: CSR; Table 14.2.4.1, Table 14.2.4.2
1.
A responder was defined as a subject that had “very much improved,” “much improved,” or “improved” on both sides of the
face.
2.
Confidence interval calculated using Clopper-Pearson method (based on binomial distribution).
Note: N = number of subjects; n = number of subjects in specific category. Percentages calculated as 100 × (n/N) out of the number
of subjects at each visit. Global Aesthetic Improvement Scale was first assessed in Group B at Month 19. Group A subjects were
untreated in Study 43USSA1812 but received Sculptra Aesthetic in this extension study; Group B subjects received Sculptra
Aesthetic in Study 43USSA1812 but were untreated in this extension study.
4. Pediatric Extrapolation
In this premarket application, existing clinical data was not leveraged to support approval
of a pediatric patient population.
D. Financial Disclosure
The Financial Disclosure by clinical investigators regulation (21 CFR 54) requires
applicants who submit a marketing application to include certain information concerning
the compensation to, and financial interests and arrangement of, any clinical investigator
conducting clinical studies covered by the regulation.
Clinical study 43USSA1812 included thirteen investigators; with two having disclosable
financial interests/arrangements and one blinded evaluator as defined in section 54.2(f) as
described below:
x Compensation to the investigator for conducting the study where the
value could be influenced by the outcome of the study: [0
investigators]
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 34 of 40
x Significant payment of other sorts: [3 investigators]
x Proprietary interest in the product tested held by the investigator: [0
investigators]
x Significant equity interest held by investigator in sponsor of covered
study: [0 investigators]
Therefore, approximately 77% of sites (10 out of 13) did not report financial interests. Of
the investigator sites that disclosed financial interests, they did not enroll the majority of
subjects (34/149). Enrollment for each of the study sites ranged from 4-13%, therefore no
study site had a majority of the subject population which minimizes the potential effect that
a single site could have on the study results. To further mitigate any potential bias, the
primary effectiveness endpoint was measured by a blinded independent evaluator in which
treatment of the subject was concealed.
The applicant has adequately disclosed the financial interest/arrangements with clinical
investigators. Statistical analyses were conducted by FDA to determine whether the
financial interests/arrangements had any impact on the clinical study outcome. The
information provided does not raise any questions about the reliability of the data
DI. SUMMARY OF SUPPLEMENTAL CLINICAL INFORMATION
Sculptra Post-Marketing Safety Data
There has been no significant change in AE and SAE reporting frequencies for
spontaneously reported adverse events. As such, the safety profile of the product and
benefit/risk ratio is judged to remain unchanged.
DII. PANEL MEETING RECOMMENDATION AND FDA’S POST-PANEL ACTION
In accordance with the provisions of section 515(c)(3) of the act as amended by the Safe
Medical Devices Act of 1990, this PMA was not referred to the General and Plastic Surgery
Devices Advisory Panel, an FDA advisory committee, for review and recommendation
because the information in the PMA substantially duplicates information previously
reviewed by this panel.
DIII. CONCLUSIONS DRAWN FROM PRECLINICAL AND CLINICAL STUDIES
A. Effectiveness Conclusions
Assessment of product effectiveness is based on the results of Pivotal Study NCT
04124692 submitted to PMA P030050 and presented in the Sculptra Instructions for
Use. Conclusions drawn from clinical study 43USSA1812 and the extension provide a
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 35 of 40
reasonable assurance that the device is effective when used for the correction of lines
and wrinkles in the cheek region in subjects over the age of 21.
Conclusions from the Base study (0 to 12 months) and Extension Study (12 to 24
months) are:
x Sculptra, reconstituted in 8 mL SWFI + 1 mL of lidocaine HCl, was effective in
the correction of cheek wrinkles, based on assessment of aesthetic improvement
and satisfaction by subjects and Investigators.
x Sculptra, reconstituted with 8 mL SWFI + 1 mL lidocaine HCl, demonstrated a
statistically significantly higher responder rate based on the GCWS At Rest
(Blinded Evaluator) at Month 12 compared with the control group (70.7% versus
25.9%, respectively; p<.0001).
x A statistically significantly higher responder rate for the treatment group compared
with the control group based on the GCWS At Rest (Blinded Evaluator) was
observed at Months 7 (66.2% versus 38.6%, respectively; p = 0.0043) and 9 (70.6%
versus 31.1%, respectively; p<.0001).
x Response rates based on the GCWS At Rest (Blinded Evaluator) for Extension
study Group B subjects were 84.8% at Month 19, 76.9% at Month 21, and 76.9%
at Month 24 demonstrating effectiveness up to Month 24.
x A statistically significantly higher responder rate for the treatment group compared
with the control group based on the GCWS Dynamic (Blinded Evaluator) was
observed at Months 7 (67.5% versus 27.3%, respectively; p<.0001), 9 (64.7%
versus 22.2%, respectively; p<.0001), and 12 (70.5% versus 28.3%, respectively;
p<.0001).
x The Month 12 improvement rates based on independent photographic review for
the left and right cheeks were 53.6% (45/84 subjects; 95% CI: 42.4, 64.5) and
57.1% (48/84 subjects; 95% CI: 45.9, 67.9), respectively, for the treatment group
and 29.5% (13/44 subjects; 95% CI: 16.8, 45.2) and 34.1% (15/44 subjects; 95%
CI: 20.5, 49.9) for the control group.
x The percentage of responders (as assessed by the GAIS - Treating Investigator)
ranged from 68.1% to 96.3% across Month 1 through Month 12 for the treatment
group and from 4.3% to 6.8% across Month 7 through Month 12 for the control
group. Excluding Month 1, CIs were >80% for the treatment group from Month 2
through Month 12.
x The percentage of responders (as assessed by the GAIS - Treating Investigator)
ranged from 93.8% to 97.0% across Month 19 (first assessment time point) through
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 36 of 40
Month 24 for Group B, with CIs >80% for Extension study Group B from Month
19 through Month 24.
x The percentage of responders (as assessed by the GAIS – subject assessment)
ranged from 57.4% to 93.5% across Month 1 through Month 12 for the treatment
group and from 6.5% to 7.0% across Month 7 to Month 12 for the control group.
Excluding Months 1 and 2, CIs were >80% for the treatment group from Month 3
through Month 12.
x The percentage of responders (as assessed by the GAIS – subject assessment)
ranged from 86.2% to 93.8% across Month 19 through Month 24 for Extension
study Group B, with CIs >80% for Group B at Month 21.
x Across Month 7 to Month 12, subject satisfaction questionnaire results showed that
the majority of subjects in the treatment group would choose to receive the
treatment again (range: 84.4% to 89.4%).
x Based on the Satisfaction with Cheeks FACE Q™ Questionnaire Rasch-
transformed scores, subjects were more satisfied with how their cheeks looked
following treatment at all post-baseline visits from Month 1 through Month 12
(mean increase from baseline range: 21.3 to 40.0), whereas subjects in the control
group were not more satisfied with how their cheeks looked at all post-baseline
visits from Month 7 through Month 12 (mean decrease from baseline range: -3.6 to
-4.1).
x Based on subject diaries, the median time to feeling comfortable returning to social
engagement across the 4 treatment sessions ranged from 3.9 hours (treatment 1) to
7.1 hours (treatment 4).
B. Safety Conclusions
Assessment of product safety is based on the results of the Pivotal Study
NCT04124692 submitted to PMA P030050 and supplements as presented in the
Sculptra Instructions for Use. The safety of using Sculptra for correction of fine lines
and wrinkles in the cheek region has been evaluated in clinical studies 43USSA1812
and the extension.
Conclusions from the Base study (0 to 12 months) are:
x Sculptra, reconstituted with 8 mL SWFI + 1 mL lidocaine HCl, was generally
safe and well tolerated.
x A total of 43 (44.3%) subjects in the treatment group and 3 (5.8%) subjects in
the control group experienced at least 1 AE during the study. The only AE
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 37 of 40
experienced by >5.0% of subjects in the treatment group was injection site
bruising (11.3%).
x Twenty (20.6%) subjects in the treatment group experienced an AE considered
related to study product or injection procedure. The most common (>1.0% of
subjects) related AEs were injection site bruising (11 [11.3%] subjects),
dizziness (2 [2.1%] subjects), and headache (2 [2.1%]) subjects.
x
All AEs related to study product or injection procedure were mild or moderate
in intensity. Three (3.1%) subjects experienced related AEs of moderate
intensity (1 subject experienced 2 events of moderate injection site pain, 1
subject experienced moderate dizziness, and 1 subject experienced moderate
injection site bruising); all events resolved by the end of the study.
x
One subject experienced 2 treatment-emergent AEs of injection site nodule (1
on the left cheek and 1 on the right cheek) and 1 subject experienced a
treatment-emergent AE of skin mass (small lump on lower left cheek, near
corner of mouth). Each event was considered mild in intensity, related to study
product and/or injection procedure, and no action was required.
x
Three (3.1%) subjects in the treatment group experienced treatment-emergent
SAEs (1 subject experienced osteoarthritis, 1 subject experienced back pain,
and 1 subject experienced obstruction gastric and small intestine
adenocarcinoma [this event also led to premature study discontinuation]); all
SAEs were considered unrelated to study product or injection procedure. No
subject died during the study.
Conclusions from the Extension Study (12 to 24 months) are:
Sculptra, reconstituted with 8 mL SWFI + 1 mL lidocaine HCl, was generally safe
and well tolerated up through 24 months.
x A total of 9 (23.1%) subjects in Group A experienced an AE considered
related to study product or injection procedure. No subject in Group A
experienced an AE with late onset (>21 days after the most recent treatment),
an AESI, or an AE leading to study discontinuation.
x A total of 15 (20.8%) subjects in Group B experienced at least 1 AE. One
subject (1.4%) experienced an AE with late onset (>21 days after the most
recent treatment) related to study product or injection procedure in the Base
study and was ongoing when enrolled in the extension study. The subject
withdrew prior to the AE resolving.
x No subject in Group B experienced an AESI or an AE leading to study
discontinuation.
x No subjects in the extension study experienced an SAE considered related to
study product or procedure.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 38 of 40
C. Benefit-Risk Determination
The probable benefits of the device are also based on data collected in the clinical
studies conducted to support PMA approval as described above. The primary potential
benefit of the device is a perceived improvement in the visual appearance of fine lines
and wrinkles in the cheek region, as assessed by the blinded Evaluator using GCWS At
Rest and Dynamic, improved global aesthetic appearance according to investigator and
subject GAIS assessments, and subject satisfaction with treatment per the FACE-Q
questionnaire and subject satisfaction questionnaire.
The probable risks of the device are also based on data collected in the clinical studies
conducted to support PMA approval as described above. The risks associated with
correction of fine lines and wrinkles in the cheek region using Sculptra primarily
include injection site reactions (e.g., pain, tenderness, redness, bruising, swelling,
itching, lumps/bumps). Most of the pre-defined, expected post-treatment events were
tolerable in severity, and resolved within 14 days.
1. Patient Perspective
Patient perspectives considered during the review included:
x At 12 months, 92.0% (81/88) of the treatment group subjects
reported improvement in the overall aesthetic appearance of the
fine lines and cheek wrinkles on the GAIS. Most treatment group
subjects continued to report improvement on the GAIS at 24
months (86.2% (56/65)).
x Based on the Satisfaction with Cheeks module of the FACE-Q
™ Questionnaire Rasch-transformed scores, subjects were
more satisfied with how their cheeks looked following
treatment at all post-baseline visits from Month 1 through
Month 24 (mean increase from baseline range: 21.3 to 40.0)
x Subjects reported the median time to feeling comfortable
returning to social engagement across the 4 treatment sessions as
3.9 hours (Treatment 1) to 7.1 hours (Treatment 4).
In conclusion, given the available information above, the data support that for correction
of fine lines and wrinkles in the cheek region the probable benefits outweigh the
probable risks.
D. Overall Conclusions
The data in this application support the reasonable assurance of safety and effectiveness
of this device when used in accordance with the indications for use.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 39 of 40
DIV. CDRH DECISION
CDRH issued an approval order on April 18, 2023.
The applicant’s manufacturing facilities have been inspected and found to be in compliance
with the device Quality System (QS) regulation (21 CFR 820).
DV. APPROVAL SPECIFICATIONS
Directions for use: See device labeling.
Hazards to Health from Use of the Device: See Indications, Contraindications, Warnings,
Precautions, and Adverse Events in the device labeling.
Post-approval Requirements and Restrictions: See approval order.
PMA P030050/S039: FDA Summary of Safety and Effectiveness Data 40 of 40
