A Randomized, Evaluator-blinded, No-treatment Controlled, Multicenter Study to Evaluate the Effectiveness and Safety of Sculptra Aesthetic for Correction of Cheek Wrinkles.
Phase: NA
Conditions: Cheek Wrinkles
Sponsor: Galderma R&D

Page 1 of 70
A randomized, evaluator-blinded, no-treatment controlled, multicenter
study to evaluate the effectiveness and safety of Sculptra
Aesthetic for correction of cheek wrinkles
Study products:
Sculptra®Aesthetic 
Clinical trial number (CTN):
43USSA1812
Sponsor:
Q-Med AB
Seminariegatan 21
SE-752 28 Uppsala, Sweden
Telephone:
+46 18 474 90 00
Facsimile:
+46 18 474 90 01
Confidentiality Statement
This investigational plan contains confidential information belonging to Q-Med AB. Except as may 
be otherwise agreed to in writing, by accepting or reviewing these materials, you agree to hold such 
information in confidence and neither disclose it to any third parties (except where required by 
applicable law) nor use it for any other purpose than in relation to the clinical study described 
herein. 
 
  
 
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Investigators and Study Administrative Structure
Further details on all participating Investigators and the complete administrative structure of the study
are found in the study files. Note that administrative changes are to be documented in the study files 
without requiring a Clinical Investigational Plan (CIP) amendment.
Sponsor:
Q-Med AB
Seminariegatan 21
SE-752 28 Uppsala, Sweden
Telephone:
+46 18 474 90 00
Medical expert:
Global Head of Clinical 
Development:
Sponsor’s Clinical Project 
Manager :
Sponsor’s Statistician:
 
  
 
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PPD
PPD
PPD
PPD

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Sponsor Signatures
The CIP is electronically signed in the document management system within the Q-Med AB quality 
management system by the representatives listed below.
Head of Clinical Scientists and Clinical Standards, Q-Med AB
Medical Expert, Q-Med AB
Statistician, Q-Med AB
 
  
 
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PPD

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Synopsis
Title of study:
A randomized, evaluator-blinded, no-treatment controlled, multi-center 
study to evaluate the effectiveness and safety of Sculptra Aesthetic for 
correction of cheek wrinkles.
Study population:
Women or men over 21 years of age with the intent to undergo 
correction of cheek wrinkles. 
Countries involved, 
number of 
sites/country:
United States, up to 13 sites
Number of subjects:
150 subjects 
Study Design
This is a prospective, randomized, evaluator-blinded, no-treatment 
controlled study. Approximately 150 subjects will be randomized (2:1) 
to either treatment with Sculptra Aesthetic (Treatment Group) or no 
treatment (Control Group), 100 subjects to treatment with Sculptra 
Aesthetic and 50 subjects to no treatment. At least 15 subjects will be 
Fitzpatrick skin type (FST) IV, and a least 14 will be FST V-VI.
Effectiveness and safety data will be collected for up to 12 months 
following the initial treatment.
All subjects will be offered to participate in an open extension study 
beginning after successful completion of this study. Subjects in the no-
treatment control group will be offered treatment with Sculptra
Aesthetic in the extension study. Subjects in the treatment group will 
continue to be followed for additional data collection as described in the 
extension study protocol.  
Primary Effectiveness
Objective and 
Endpoint:
To evaluate the effectiveness of Sculptra Aesthetic versus a no-
treatment control in the correction of cheek wrinkles.
Secondary 
Effectiveness
Objective(s) and 
Endpoint(s):
To evaluate the effectiveness of Sculptra Aesthetic versus a no-
treatment control in the correction of cheek wrinkles.
Endpoints:
 
  
 
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a. Combined oral contraceptives (estrogens and progesterone) or 
implanted or injectable contraceptives with a stable dose for at least 28 
days prior to the Baseline visit
b. Hormonal or copper intrauterine device (IUD) inserted at least 28 
days prior to the Baseline visit
c. Barrier methods of contraception: condom or occlusive cap 
(diaphragm or cervical caps) with spermicidal 
foam/gel/film/cream/suppository
d. Bilateral tubal ligation prior to the Baseline visit 
e. Vasectomized partner (in monogamous relationships) for at least 3 
months prior to the Baseline visit 
f. Strict abstinence (at least one month prior to baseline and agrees to 
continue for the duration of the study or use acceptable form of birth 
control).
Exclusion criteria:
The presence of any of the following exclusion criteria will exclude a 
subject from enrollment in the study:
1.
Known/previous allergy or hypersensitivity to any of the 
Sculptra Aesthetic constituents.
2.
Known/previous allergy or hypersensitivity to lidocaine and 
other local anesthetics, e.g. amide-type anesthetics or topical 
anesthetics agents.
3.
Previous or present multiple allergies or severe allergies, such as 
manifested by anaphylaxis or angioedema, or family history of 
these conditions.
4.
Previous tissue augmenting therapy, contouring or revitalization 
treatment in the face, except the lips, with any of the following 
filler prior to Baseline visit:
a.
Collagen, Hyaluronic Acid – 12 months
b.
Calcium Hydroxyapatite (CaHa), Poly L- Lactic Acid 
(PLLA) or permanent (non-biodegradable)- Prohibited
5.
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 
 
  
 
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exposes the study subject to undue risk by study participation, 
e.g.: 
a.
Resurfacing 
(laser, 
photomodulation, 
light, 
radiofrequency, 
ultrasound, 
chemical 
peel, 
dermabrasion, 
or 
other 
ablative/non-
ablative 
procedures)
b.
Needling or mesotherapy 
c.
Cryotherapy
d.
Neurotoxin injections
e.
Lipolytic injections (e.g. dexycholic acid or other 
lipolytic substances)
f.
Dental work, such as root canals or sinus surgery 
or is planning to undergo any of these procedures affecting the 
treatment area, at any time during the study.
6.
Presence of any disease or lesions near or on the area to be 
treated, e.g.
a.
Inflammation, active or chronic infection in or near the 
treatment area
b.
Facial psoriasis, eczema, acne, rosacea, perioral 
dermatitis, herpes zoster/ herpes simplex and acanthosis
c.
Scars or deformities
d.
Cancer or precancerous condition (e.g. actinic keratosis 
or actinic cheilitis)
7.
History of severe elastosis and/or excessive sun exposure that in 
the opinion of the Treating Investigator, could affect the safety 
and effectiveness outcome of the study.
8.
History of bleeding disorders or treatment with anticoagulants or 
inhibitors of platelet aggregation (e.g. aspirin or other NSAIDs), 
Omega-3, or vitamin E within 14 days before treatment. Omega 
3 and Vitamin E are acceptable only as part of a standard 
multivitamin formulation.
9.
Treatment with chemotherapy, immunosuppressive agents 
(inhaled corticosteroids allowed), immunomodulatory therapy 
(e.g. monoclonal antibodies or antiviral treatment for HIV or 
Hepatitis C) within 6 months before treatment. 
 
  
 
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10. Use of topical corticosteroids or topical prescription retinoids (in 
the treatment area) within 1 month of the Baseline visit or 
systemic retinoid treatment within 6 months of the Baseline visit.
11. Previous surgery including plastic surgery, lifting threads, tissue 
grafting or tissue augmentation with permanent implants, 
silicone or fat, or tattoo, affecting the treatment area.
12. History of cancer or previous radiation near or on the area to be 
treated.
13. HIV positive or active hepatitis.
14. History of or active collagen diseases such as systemic lupus 
erythematosus, 
rheumatic 
arthritis, 
polymyositis, 
dermatomyositis, skin or systemic scleroderma.
15. Tendency to form keloids, hypertrophic scars, or any other 
healing disorder.
16. Presence of piercing, beard or facial hair that could interfere with 
study evaluation.
17. Abnormal result on functionality, sensation, symmetry, mass 
formation or palpation assessments in the treatment area. 
18. Abnormal result on extraocular muscle function test or 
confrontational visual field assessment.
19. Presence of a dental, oral, or facial condition which, in the 
Treating Investigator’s opinion, would interfere with the study 
injections and/or study assessment, e.g. has dentures or any 
device covering all or part of the upper palate, and/or severe 
malocclusion or dentofacial or maxillofacial deformities.
20. Woman who is pregnant (confirmed by positive urine pregnancy 
test/serum pregnancy test), breast-feeding or intend to become 
pregnant over the duration of the study.
21. Any medical condition that, in the opinion of the Treating 
Investigator, would make the subject unsuitable for inclusion 
(e.g. a chronic, relapsing or hereditary disease that may interfere 
with the outcome of the study).
22. Other condition preventing the subject from entering the study in 
the Treating Investigator’s opinion, e.g. subjects failing baseline 
safety assessments, subjects not likely to avoid other cosmetic 
treatments in the treatment area, subjects anticipated to be 
unavailable or incapable of understanding the study assessments 
or having unrealistic expectations of the treatment result.
 
  
 
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23. Study site personnel, close relatives of the study site personnel 
(e.g. parents, children, siblings, or spouse), or employees and 
close relatives of employees at the Sponsor company.
24. Participation in any interventional clinical study within 30 days 
of screening.
Investigational 
product:
Sculptra Aesthetic is a sterile, freeze-dried, injectable poly-L-lactic acid
(PLLA) with excipients. Each vial of dry powder contains: 
150 mg PLLA
90 mg sodium carboxymethylcellulose
127.5 mg of non-pyrogenic mannitol
The contents in one vial will be reconstituted prior to use by the 
addition of 8 mL of sterile water for injection (SWFI) at the 
investigational site.
Immediately prior to injection, 1 mL of 2% lidocaine will be added to 
make a total volume of 9 mL.
Reference therapy:
No treatment.
Treatment regimen
and location of treated 
area:
Each subject in the treatment group will receive a single regimen of 
Sculptra Aesthetic. A single regimen consists of up to four (4) injection 
sessions with 1-month (+5 week) intervals. Sculptra Aesthetic will be 
administered using a 25G (gauge) needle using the bolus, fanning, 
cross-hatching, linear threading injection technique or other techniques
at the discretion of the Treating Investigator.  Injections will be made
subdermally, i.e. in the subcutaneous and supraperiosteal region. A 
maximum of 18 mL (2 vials) of Sculptra Aesthetic will be administered 
per treatment session with a maximum of 9 mL (1 vial) per cheek, 
evenly distributed within the treatment area.
The treatment area is within the following borders:
 Superior border - from top of tragus to top of alar crease
 Medial border - from top of the alar crease, along the nasolabial fold 
(NLF) to the inferior border of the mandibular ramus
 Inferior border - from medial border at mandibular ramus to angle of 
mandibular ramus
 Lateral border - from angle of mandibular ramus to top of tragus
Effectiveness
Assessment(s):
1. Cheek wrinkles by Blinded Evaluator using 
 
2. Cheek wrinkles by Treating Investigator using 
 
3. Global aesthetic improvement by Treating Investigator and Subject 
using GAIS.
 
  
 
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4. Improvement in cheek wrinkles by Central Independent Photographic 
Reviewer.
5. Subject’s satisfaction after treatment using a Subject Satisfaction 
Questionnaire.
6. Subject’s satisfaction using FACE-Q “Satisfaction with Cheeks”.
7. Lifting effect of cheek using 3D imaging 
8. Return to social engagement after treatment using subject diaries.
9. Dermal thickness using Ultrasound. 
10. Radiance, skin tightness and jawline contour assessed live by 
Treating Investigator.
Safety Assessment(s):
1. Adverse Event reporting: AEs will be obtained from signs and 
symptoms reported by the subjects or detected during each examination.
2. A subject diary will be dispensed to all subjects in the treatment 
group for daily completion for 28 days beginning on injection day for 
each treatment with direct questioning for pain, tenderness, redness, 
bruising, swelling, itching, lumps/bumps and “other”. Subjects will be 
specifically asked to record any of the following symptoms in the other 
section; changes in vision (i.e. loss of vision, blurriness, double vision, 
pain in or around your eye, blindness, blind spots, problems moving 
your eyes), skin changing color around the eyelids, crusty or scabby 
skin around the eyelids, pain, headache, fever, dizziness, confusion, 
weakness or numbness in the arms or legs, changes to consciousness or 
alertness, difficulty speaking/ speech impairment and face droop.
3. Functionality, sensation, firmness, symmetry, mass formation and 
palpation tests according to pre-defined methods, at baseline and at each 
on-site follow-up visit.
4. Device deficiencies will be assessed at treatment visits.
5. Visual function assessments will be performed before and 30 minutes 
following injection and at all scheduled follow up visits.
Statistical Methods: 
Principles for the analysis
For a significant result, the two-sided p-value of the comparison of 
responder rates between the treated and untreated subjects at month 12
using the Fisher’s exact test needs to be smaller than 0.05. The 
estimates of the responder rate in each treatment group will be 
presented along with the difference in responder rates. Corresponding 
confidence intervals for both responder rates and difference in 
responder rates and p-value for difference in responder rates will also be 
presented. 
 
  
 
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The secondary endpoints of 
) as assessed 
live by the Blinded Evaluator will be analyzed in the same way. Results 
for the right and left side of the face separately as well as combined will 
be presented.
All other secondary effectiveness endpoints will be analyzed 
descriptively, including 95% confidence intervals.
All safety endpoints will be analyzed descriptively.
Sample size
A total sample size of approximately 150 subjects will be included in 
this study; approximately 100 will be randomized to treatment with 
Sculptra Aesthetic and approximately 50 will be randomized to no 
treatment. Sample size justifications are given below.
Previous data
Since the primary endpoint will be based on a new scale, no existing 
data is available.
Assumptions: Based on what is seen in clinical studies of injectable 
fillers in the facial areas, it is reasonable to assume a responder rate of 
at least 70% in the Sculptra Aesthetic treatment group at month 12. For 
the no treatment control group, responder rates up to almost 30% have
been observed in data on file. Based on this, it is assumed that the 
response rate will be maximum 35% in the no-treatment control group 
at month 12.
Sample size calculation
For the responder rate in 
, testing the difference using a two-
sided test at the 5% significance level will have approximately 90% 
power to demonstrate difference between a responder rate of 70% in the 
Sculptra Aesthetic group, and a responder rate of 35% in the no 
treatment control group when the sample sizes are 84 and 42, 
respectively. Accounting for 15% drop-outs, approximately 150 
subjects need to be randomized in a 2:1 ratio.
 
  
 
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Study flow chart
Title 
Doc id  
CIP 43USSA1812 Sculptra Cheek Wrinkles
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Abbreviations and Definitions of Terms
AE
AESI
Adverse event 
Adverse Event of Special Interest
Blinded evaluator
An evaluator responsible for independent evaluation of treatment 
result(s). The evaluator must not be involved in the treatment of the 
subject.
CFR
CIP
CMC
Code of Federal Regulations
Clinical Investigational Plan
Sodium carboxymethylcellulose 
CRO
Contract research organization
CTA
Clinical trial agreement
CTN
Clinical trial number
CV
Curriculum vitae
Device deficiency
Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance (includes malfunctions, 
use errors, and inadequate labelling)
DMP
Data management plan
eCRF
Electronic case report form
FSFV
First Subject First Visit, i.e. first subject who signs the informed 
consent form
FST
Fitzpatrick skin type 
G
Gauge
GCP
Good clinical practice 
GDPR
General Data Protection Regulation
HCl
Hydrochloride
ICH
International Conference on Harmonization
IFU
Instructions for use
Investigational product
Medical device being assessed for safety or performance in a study. 
“Investigational product” is the same as “study device”, 
“investigational device”, or ”investigational medical device”.
Institution
Any public or private entity or agency or medical or dental facility 
where a clinical study is conducted.
Investigator
The Principal Investigator (PI) or other qualified person, i.e. sub-
Investigator, designated and supervised by the PI at a study site to 
perform critical study-related procedures or to make important study-
related decisions as specified on the signature and delegation log
Investigator file
Essential documents relating to a clinical study as defined in 
applicable GCP guidance document and maintained by the 
Investigator.
 
  
 
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IRB
Institutional review board
ISO
International Organization for Standardization
LSFV
Last Subject First Visit
LSLV
Last Subject Last Visit
MedDRA
Medical dictionary for regulatory activities
NLF
Nasolabial fold
NSAID
Non-steroidal anti-inflammatory drugs
PI
Principal Investigator; qualified person responsible for conducting 
the study at a study site
PP
Per protocol
RA
ROPI
Regulatory authority
Report of Prior Investigations
SAE
Serious adverse event
Sponsor file
Essential documents relating to a clinical study as defined in 
applicable GCP guidance document and maintained by the Sponsor.
Study files
The Investigator file and the Sponsor file
Study product
The investigational product
Study site
SWFI
Institution or site where the study is carried out
Sterile water for injection
USP
United States Pharmacopeia
WHO
World Health Organization
 
  
 
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Table of Contents
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE
2
SYNOPSIS
4
STUDY FLOW CHART
13
ABBREVIATIONS AND DEFINITIONS OF TERMS
14
TABLE OF CONTENTS
16
LIST OF TABLES
20
1
ETHICAL CONSIDERATIONS
21
1.1
Statement of ethical compliance
21
1.2
Application to institutional review board and regulatory authorities
21
2
BACKGROUND INFORMATION
21
2.1
Indication and population description
21
2.2
Study Product Profile
22
2.2.1
Investigational product description
22
2.3
Study rationale and justification for design
22
2.4
Risks and benefits
23
3
OBJECTIVE(S) AND ENDPOINT(S)
24
3.1
Effectiveness objective and endpoints
24
3.1.1
Primary effectiveness endpoint
24
3.1.2
Secondary effectiveness endpoints
24
3.2
Safety objective and endpoints
25
4
DESIGN OF THE STUDY
25
4.1
General outline
25
4.2
Number of subjects
26
4.3
Duration of subject participation
26
4.4
Randomization and blinding
26
4.4.1
Randomization
26
4.4.2
Blinding
26
4.4.3
Emergency unblinding
27
4.5
Medical history
27
4.6
Prior and concomitant therapies
27
4.6.1
Definition
27
4.6.2
Categories
27
4.6.3
Recording
27
4.6.4
Authorized concomitant therapies
27
 
  
 
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4.6.5
Prohibited concomitant therapies
27
4.7
Visits
29
4.7.1
Visit 1, Screening (Day 30 to Day 1) all subjects
31
4.7.2
Visit 2, Baseline and First Treatment (Day 1) all subjects
31
4.7.3
Visit 2a, Follow up 72 hour telephone call (±24 hours) for treatment group only
32
4.7.4
Visit 3, Treatment 2 (1 month (+5 weeks) after Treatment 1) for treatment group only
32
4.7.5
Visit 3a, Follow up 72 hour telephone call (±24 hours) for treatment group only, subjects who received a 
second treatment.
33
4.7.6
Visit 4, Treatment 3 (1 month (+5 weeks) after Treatment 2) for treatment group only
33
4.7.7
Visit 4a, Follow up 72 hour telephone call (±24 hours) for treatment group only, subjects who received a 
third treatment.
34
4.7.8
Visit 5, Treatment 4 (1 month (+5 weeks) after Treatment 3) for treatment group only
35
4.7.9
Visit 5a, Follow up 72 hour telephone call (±24 hours) for treatment group only, subjects who received a 
fourth treatment.
36
4.7.10
Visits 6, 7 and 8, Follow up month 7 (+ 2weeks), 9 (±2 weeks), 12 (±2 weeks) all subjects
36
4.7.11
Unscheduled Visits
36
5
SUBJECTS
37
5.1
Subject information and informed consent
37
5.2
Inclusion criteria
37
5.3
Exclusion criteria
38
5.4
Subject number
40
5.5
Withdrawal of subjects
40
6
STUDY PRODUCTS
41
6.1
Investigational product
41
6.2
Reference product
42
6.3
Additional products and materials
42
6.4
Packaging, labelling, and storage
43
6.4.1
Investigational product
43
6.4.2
Reference product
43
6.4.3
Product accountability
43
6.5
Treatment
44
6.5.1
Treatment procedure
44
6.5.2
Treatment regimen (dose and interval)
45
6.5.3
Post treatment care
45
6.5.4
Post trial provisions
45
6.5.5
Treatment compliance
46
7
EFFECTIVENESS ASSESSMENTS
46
7.1
47
7.2
48
 
  
 
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7.3
Global Aesthetic Improvement Scale (GAIS)
49
7.4
Subject Satisfaction Questionnaire
50
7.5
FACE-Q “Satisfaction with Cheeks”
51
7.6
Lifting effect of cheek using 3D imaging
51
7.7
Return to social engagement
51
7.8
Ultrasound
51
7.9
Radiance, skin tightness and jawline contour assessment
52
7.10
Photography
52
7.11
Improvement in cheek wrinkles by Central Independent Reviewer
52
8
SAFETY ASSESSMENTS
52
8.1
Assessment of AEs by direct questioning to subject and evaluation of subject
53
8.2
Subject Diary Data
53
8.3
Laboratory assessments
53
8.4
Visual Function assessments
53
8.4.1
Snellen visual acuity test
54
8.4.2
Extraocular muscle function test
54
8.4.3
Confrontation visual field
54
8.5
Other safety assessments
54
8.5.1
Cheek sensation
54
8.5.2
Cheek firmness, symmetry and function
55
8.5.3
Mass formation
55
8.5.4
Device palpability only for subjects in the treatment group
55
8.6
Adverse events
55
8.6.1
Definition of an adverse event
55
8.6.2
Definition of a serious adverse event
55
8.6.3
Definition of unanticipated adverse effect
56
8.6.4
Recording instructions
56
8.6.5
Reporting of adverse events
57
8.6.6
Reporting of adverse events of special interest (AESIs)
57
8.6.7
Reporting of serious adverse events
58
8.6.8
Stopping Rule
59
8.6.9
Reporting of unanticipated adverse device effects
59
8.6.10
Follow up of unresolved events ongoing at termination of the study
59
8.6.11
Reporting and follow up of events occurring after subject termination of the study
59
8.6.12
Pregnancy
60
8.6.13
Anticipated adverse events
60
8.7
Device deficiencies
60
8.7.1
Definition of a device deficiency
60
 
  
 
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8.7.2
Recording instructions
60
8.7.3
Reporting of device deficiencies
60
9
DATA HANDLING AND MANAGEMENT
61
9.1
Data management
61
9.2
Electronic case report forms
61
9.2.1
Data entry
62
9.2.2
The query process
62
9.2.3
User identification
62
9.2.4
Audit trail
62
9.3
Source documents
62
9.4
Record keeping and access to source data
63
9.5
Document and data retention
63
10
STATISTICAL METHODS
63
10.1
General
63
10.2
Analysis populations
64
10.3
Demographics, baseline assessments, and subject characteristics
64
10.4
Effectiveness analysis
64
10.4.1
Primary effectiveness analysis
64
10.4.2
Secondary effectiveness analysis
65
10.5
Safety analysis
65
10.6
Handling of missing data
65
10.7
Data monitoring committee
66
10.8
Withdrawals and deviations
66
10.9
Sample size
66
10.9.1
Previous data
66
10.9.2
Assumptions
66
10.9.3
Sample size calculations
66
11
PROTECTION OF PERSONAL DATA
66
12
QUALITY CONTROL AND QUALITY ASSURANCE
67
12.1
Quality control
67
12.2
Quality assurance
67
12.3
Changes to the clinical investigational plan
67
13
FINANCING, INDEMNIFICATION, AND INSURANCE
68
14
PUBLICATION POLICY
68
15
SUSPENSION OR PREMATURE TERMINATION
68
16
REFERENCES
69
 
  
 
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List of Tables
Table 1 Schedule of events for Treatment Group....................................................................29
Table 2 Schedule of events for Control Group/Untreated subjects .........................................30
Table 3 Fitzpatrick Skin Types (FST) .....................................................................................31
Table 4 Grading for subject diary data ....................................................................................53
List of Appendices
Appendix 1...............................................................................................................................70
 
  
 
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1
Ethical Considerations
1.1
Statement of ethical compliance
The study shall be conducted in compliance with the clinical trial agreement (CTA), the clinical 
investigational plan (CIP), good clinical practice (GCP), and applicable regional or national 
regulations. The study shall be conducted in accordance with the ethical principles that have their 
origin in the Declaration of Helsinki (1964, and its amendments in force at the initiation of the
study) insofar as such revisions are consistent with US treaty obligations and in accordance with US 
law(1).
The study shall follow the international standard for clinical study of medical devices for human 
subjects, International Organization for Standardization (ISO) 14155 2011 as applicable for US 
regulations and the International Conference on Harmonization (ICH) guideline for GCP (E6) as 
applicable for medical device.
1.2
Application to institutional review board and regulatory authorities
It is the responsibility of the Principal Investigator (PI) to obtain approval of the
CIP/CIP amendment(s) from the institutional review board (IRB). The study shall not begin until the 
required favorable opinion from the IRB has been obtained. The PI shall file all correspondence with 
the IRB in the Investigator file and copies of IRB approvals shall be forwarded to the Sponsor. Any 
additional requirements imposed by the IRB or regulatory authorities (RA) shall be followed. 
The study requires application for approval from the US Food and Drug Administration (FDA). The 
study will not be started until the Sponsor has received written approval or until the statutory waiting 
period from the appropriate authority has elapsed. The Sponsor will provide the PI with a copy of the 
relevant document.
The collection, access to, processing, and transfer of protected health information or sensitive 
personal data shall be carried out in accordance with applicable rules and regulations.
2
Background Information
2.1
Indication and population description
Sculptra Aesthetic is indicated for use in immune competent people as single regimen for correction 
of shallow to deep nasolabial fold (NLF) contour deficiencies and other facial wrinkles. (2)
This is a 12-month study to assess the effectiveness and safety of Sculptra Aesthetic for the correction 
of cheek wrinkles. Approximately 150 subjects, out of which at least 15 will be Fitzpatrick skin type 
(FST) IV, and 14 will be FST V-VI, will be enrolled. Subjects fulfilling all inclusion criteria but no 
exclusion criteria as outlined here in the protocol will be randomized in a 2:1 ratio to either treatment 
with Sculptra Aesthetic (Treatment Group) or no treatment (Control Group).
After successful completion of the study, subjects will be offered to participate in an open extension 
study. Subjects in the no-treatment control group will then be offered treatment with Sculptra
Aesthetic. Subjects in the treatment group will continue to be followed for additional data collection 
as described in the extension study protocol. The sponsor plans to submit the clinical data obtained in 
the initial 12-month study in support of the cheek wrinkles indication to the Sculptra Aesthetic label 
as a Panel-Track supplement.
 
  
 
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Given the anticipated low level of acceptable AEs in connection with the injection, the protocol 
required safety assessments it was determined the risk-benefit assessment for use of Sculptra 
Aesthetic with the investigational plan specified reconstitution and injection procedures for correction 
of cheek wrinkles appears to offer a clinical benefit at reasonable risk.
3
Objective(s) and Endpoint(s)
3.1
Effectiveness objective and endpoints
Effectiveness objective:
To evaluate the effectiveness of Sculptra Aesthetic versus a no-treatment control in the correction of 
cheek wrinkles.
3.1.1
Primary effectiveness endpoint
3.1.2
Secondary effectiveness endpoints
1.  Responder rate based on the 
 Scale (
, as assessed live by 
the Blinded Evaluator at month 7 and 9. 
A responder is defined as a subject with at least 1 grade improvement in both cheeks concurrently 
from baseline.
2. Responder rate based on the 
 Scale
, as assessed live 
by the Blinded Evaluator at month 7, 9 and 12. 
A responder is defined as a subject with at least 1 grade improvement in both cheeks concurrently 
from baseline.
3. Improvement rate based on the Independent Photographic Reviewer’s assessment using random 
pairings of baseline and month 12 photographs.
Treatment group: An improved subject is defined as a subject for whom the Independent 
Photographic Reviewer correctly identified the month 12 photograph in the pair of pre- and post-
treatment photographs at rest.
Control group: An improved subject is defined as a subject for whom the Independent Photographic 
Reviewer identified any of the photographs in the pair as post-treatment at rest.
4. Percentage of subjects having at least “Improved” according to the Global Aesthetic Improvement 
Scale (GAIS) on both sides of the face combined, as assessed live by the subject and the Treating 
Investigator separately, at all visits following the Baseline visit for the Treatment Group and at month 
7, 9 and 12 for the Control Group.
5. Percentage of subjects responding in each response category for each question in the subject 
satisfaction questionnaire at all visits following the Baseline visit for the Treatment Group
6. Change from baseline in subject satisfaction using the Satisfaction with Cheeks FACE-Q 
questionnaire with Outcome Rasch transformed total scores as well as proportion of subjects in each 
response category for each of the individual questions at all visits following the Baseline visit for the 
Treatment Group and at month 7, 9 and 12 for the Control Group.
Responder rate based on the 
 Scale 
, as assessed live by 
the Blinded Evaluator at month 12. 
A responder is defined as a subject with at least 1 grade improvement from baseline on both cheeks 
concurrently.
 
  
 
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7. Time to return to social engagement after treatment using subject diaries for 28 days after each 
treatment.
3.2
Safety objective and endpoints
Safety objective: 
The objective is to evaluate the safety of Sculptra Aesthetic in the correction of cheek wrinkles.
Safety endpoints:

Incidence, intensity, time to onset and duration of adverse events collected throughout the study 
period.

Incidence, intensity and number of days of pre-defined expected post-treatment events collected 
using subject diaries for 28 days from each treatment.

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:
• Cheek firmness, symmetry and function (smiling and chewing)
• Device palpability (baseline assessment excluded)
• Mass formation
• Cheek sensation
• Visual Function Assessments
4
Design of the Study
4.1
General outline
This is a prospective, randomized, evaluator-blinded, no-treatment controlled study to assess the 
effectiveness and safety of treatment with Sculptra Aesthetic for correction of cheek wrinkles. All 
subjects in the Treatment Group and in the Control Group will be followed for 12 months after 
baseline.
Approximately 150 subjects with intent to undergo correction of cheek wrinkles with a 
 
 on each side of the face will be randomized (2:1) to either 
treatment with Sculptra Aesthetic (Treatment Group) or no treatment (Control Group), 100 subjects 
to treatment with Sculptra Aesthetic and 50 subjects to no treatment. At least 15 subjects will be 
Fitzpatrick skin type (FST) IV, and at least 14 will be FST V-VI. 
 
  
 
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Investigator blinding will be accomplished by using a Treating Investigator to administer the 
treatments and a Blinded Evaluator, to whom randomization and treatment are concealed, to conduct 
the blinded assessments. Safety assessments will be performed by non-blinded personnel.
Eligible subjects will perform a screening visit and baseline visit, these visits may be combined if 
appropriate. All subjects randomized to receive treatment will be injected by the Treating 
Investigator at Day 1, the procedure is outlined in section 6. Sufficient amount of product, as 
determined by the Treating Investigator, should be injected to achieve optimal correction, which is 
defined as at least a one grade improvement on the 
 Scale
At 
Rest and best correction that could be achieved as agreed upon by the Treating Investigator and the 
subject. Three additional treatment sessions may be performed if needed to achieve optimal 
correction, as determined by the Treating Investigator and subject. Treatment will stop when optimal 
correction has been achieved and subsequent visits will be follow-up visits. All subjects in both the 
treatment and the control group will return to the clinic at month 7, 9 and 12. The Schedule of Events 
is outlined in Tables 1 & 2.
4.2
Number of subjects
Approximately 150 subjects will be enrolled. The duration of the enrollment period is expected to be 
three months.
4.3
Duration of subject participation
The total duration of the study is expected to be 17 months. A subject will be involved in the study for 
up to 13.5 months. 
Note: One month is defined as 4 weeks in the study.
End of study is when enrollment has reached the target number of subjects and all subjects have 
completed the last study visit.
4.4
Randomization and blinding
4.4.1
Randomization
Approximately 150 subjects will be randomized (2:1) to either treatment with Sculptra Aesthetic
(Treatment Group) or no treatment (Control Group). At least 15 subjects will be Fitzpatrick skin type 
(FST) IV, and a least 14 subjects will be FST V-VI. Before starting the study, a randomization list 
will be prepared under the supervision of a designated statistician from the Sponsor. The 
randomization will be stratified by FST group (FST I-III, FST IV, and FST V-VI). Subjects in the 
FST I-III stratum will be further stratified by center; subjects in the FST IV and FST V-VI strata will 
not be further stratified by center due to the small sample size in these groups, randomization numbers 
will be allocated in ascending sequential order to each subject. Randomization will be performed 
using an Interactive Response System by assigning each subject to treatment group or control group
according to the randomization list.
4.4.2
Blinding
Blinding will be accomplished by using a Treating Investigator to administer the treatments and a 
Blinded Evaluator, to whom randomization and treatment are concealed, to conduct the blinded 
assessments. The Treating Investigator will not be blinded. The Blinded Evaluator is not allowed to 
discuss treatments with the Treating Investigator or subjects. No study related documents that contain 
information regarding the treatment of subjects should be available to the Blinded Evaluator. Safety 
assessments will be performed by non-blinded personnel who are qualified by training and 
experience.
 
  
 
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4.4.3
Emergency unblinding
Not applicable as the treating Investigator is not blinded to treatment. 
4.5
Medical history
History of relevant surgical events and medical conditions should be documented (including any prior 
dermatological procedures or implants) in the electronic case report forms (eCRF) using medical 
terminology.
4.6
Prior and concomitant therapies
4.6.1
Definition
Prior therapies are defined as therapies that have been used within 30 days of the Screening visit or 
within the timelines specified in the Inclusion/Exclusion criteria.
Concomitant therapies are defined as follows:

any existing therapies ongoing at the time of the Screening visit,

any changes to existing therapies (such as changes in dose or formulation) during the course 
of the study, or

any new therapies received by the subject since the Screening visit
4.6.2
Categories
The following three categories are to be considered for prior and concomitant therapies:

Drugs/therapies including but not limited to prescription, over-the-counter (OTC), birth 
control pills/patches/hormonal devices, vitamins, herbal medicines/supplements, and 
homeopathic preparations.

Medical and surgical procedures including, but not limited to dental work, such as root canals 
or sinus surgery

Aesthetic procedures including, Resurfacing (laser, photomodulation, light, radiofrequency, 
ultrasound, chemical peel, dermabrasion, or other ablative/non- ablative procedures, needling 
or mesotherapy, cryotherapy, neurotoxin injections, lipolytic injections (e.g. dexycholic acid 
or other lipolytic substances), previous tissue augmenting therapy, contouring or 
revitalization treatment in the face.
4.6.3
Recording
Prior and concomitant therapies are to be recorded in source documents and on the appropriate form
in the eCRF. Concomitant therapies are to be recorded, reviewed, and updated at each visit. Any new 
concomitant therapy or modification of an existing therapy may be linked to an AE. A corresponding 
AE form must be completed to account for the change in therapy, except in some cases such as 
therapy used for prophylaxis, or dose modification for a chronic condition.
4.6.4
Authorized concomitant therapies
Unless listed in prohibited concomitant therapies (Section 4.6.5), all therapies are authorized.
4.6.5
Prohibited concomitant therapies
The following therapies are prohibited during the study because they may interfere with the 
effectiveness and/or safety assessment of the study product(s) and/or injection procedure:
 
  
 
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
Anticoagulants or inhibitors of platelet aggregation that have the ability to prolong bleeding 
times (e.g. aspirin, non-steroidal anti-inflammatory drugs [NSAIDs]), Omega-3 or Vitamin E 
should not be used within 14 days before any treatment to avoid increased bruising or 
bleeding at injection sites. Omega 3 and Vitamin E are acceptable only as part of a standard 
multivitamin formulation.

Chemotherapy, immunosuppressive agents (inhaled corticosteroids allowed) or 
immunomodulatory therapy (e.g. monoclonal antibodies or antiviral treatment for HIV or 
Hepatitis C).

Prescribed corticosteroids or prescription retinoids for topical use in the treatment area or 
systemic use.

Planned aesthetic facial plastic surgery (e.g. surgery to either the upper or lower lip, facelift, 
rhinoplasty, facial liposuction etc.) or cosmetic procedures (e.g. lifting threads, tissue grafting, 
tissue augmentation with permanent implants, silicone, or fat)

Treatment/procedure in the face that would interfere with the study injections and/or study 
assessments or exposes the study subject to undue risk by study participation, e.g.:
a. Resurfacing (laser, photomodulation, intense pulsed light (IPL), radiofrequency, 
ultrasound, chemical peel, dermabrasion, needling, or other ablative/non- ablative procedures)
b. Needling or mesotherapy
c. Cryotherapy
d. Neurotoxin injections (glabella or forehead lines treatment allowed)
e. Lipolytic injections (e.g. dexycholic acid or other lipolytic substances)
f. Planned oral surgery or dental work, such as root canals or sinus surgery, tattoo or piercing 
in the area to be treated 

Tissue augmenting therapy, contouring or revitalization treatment in the face, except the lips; 
a.
with Collagen or Hyaluronic Acid 
b.
with Calcium Hydroxyapatite (CaHa), Poly L- Lactic Acid (PLLA) or permanent (non-
biodegradable

Participation in any interventional clinical study. 

The study product contains lidocaine, but additional local anesthesia may be used. Lidocaine 
should however be used with caution in subjects receiving other local anesthetics or agents 
structurally related to amide-type anesthetics, e.g. certain anti-arrhythmics, as the systemic 
toxic effects can be additive.
If a prohibited therapy becomes a necessary treatment for the safety or best interest of the subject, the 
Sponsor should be notified, time permitting, to discuss possible alternatives prior to administration of 
a prohibited therapy.
If a subject receives prohibited therapy during the clinical study, the Sponsor should be notified to 
discuss the pertinence and the modalities for the subject to continue in the clinical study.
 
  
 
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4.7.1
Visit 1, Screening (Day -30 to Day 1) - all subjects
The screening visit and baseline visit (Day 1) may be performed on the same day.The following 
activities and screening assessments will be performed within 30 days priorto baseline.
o
Obtain Informed Consent prior to conducting any study specific procedure.
o
Assess eligibility: Review inclusion/exclusion criteria.
o
Record the subject’s medical history (including any prior dermatological procedures or 
implants).
o
Record the subject’s prior and concomitant therapies.
o
Obtain demographic and baseline data: date of birth, height, weight, gender, ethnicity, race 
and Fitzpatrick Skin Type (FST). 
o
FST is a skin classification system that categorizes different skin colors, and their 
reactions to ultraviolet light. (9, 10). For determination of the FST, see Table 3
below.
o
Height may be self-reported, weight is to be measured at clinic. 
o
Assess 
): Treating Investigator and Blinded Evaluator
o
Perform safety assessments: Cheek sensation, Cheek firmness, symmetry and function, 
Mass formation
o
Perform Visual Function Assessments (Snellen visual acuity, Extraocular muscle function 
and Confrontation visual field tests) for all subjects (prior to treatment for subjects in the 
treatment group).
o
For all females of childbearing potential, perform Urine Pregnancy Test (UPT) prior to 
treatment.  Test result must be negative for the subject to be eligible for treatment. 
o
Schedule the baseline and treatment visit (Day 1) if performed on a different day than 
screening.  
4.7.2
Visit 2, Baseline and First Treatment (Day 1) - all subjects
The screening visit and baseline visit (Day 1) may be performed on the same day. If Screening 
visit and Baseline visit are not performed on the same day, the following should be repeated:
o
Review for changes in concomitant therapies.
o
Re-confirm eligibility criteria
o
Obtain weight measured at clinic.
 
  
 
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o
Assess 
) Treating Investigator and Blinder Evaluator
o
Perform Urine Pregnancy test for all females of childbearing potential (prior to treatment).
Test result must be negative for the subject to be eligible for treatment. 
Once the subject is deemed eligible by the Treating Investigator, the following procedures should be 
completed:
o
Randomize the subject.
o
Perform safety assessments: Cheek sensation, Cheek firmness, symmetry and function, 
Mass formation
o
Perform Visual Function Assessments (Snellen visual acuity, Extraocular muscle function 
and Confrontation visual field tests) for all subjects (prior to treatment for subjects in the 
treatment group).
o
Obtain pre-treatment Photography (2D and 3D).
o
Instruct the subject to complete Face-Q assessment (pre-treatment)
o
Perform pre-treatment ultrasound (at selected sites).
o
Instruct the subject to complete the FACE-Q questionnaire.
o
Sculptra Aesthetic administration (treatment group only).  
o
Evaluate for device deficiencies (treatment group only).
o
Dispense diary and instruct subject on daily Diary completion. Remind subject to bring 
the Diary to the next on-site visit (treatment group only).
o
30 minutes following injection, perform Visual Function Assessments (treatment group 
only).
o
Evaluate the subject for post-treatment AEs- Treating Investigator.    
o
Schedule the next follow up visit (1 month (+5 weeks) for treatment group) / (Month 7
(+2 weeks) for control group) 
4.7.3
Visit 2a, Follow up 72 hour telephone call (±24 hours) - for treatment group 
only
o
Interview subject regarding any concomitant therapies
o
Interview subject regarding any AEs that have occurred since receiving treatment. If AEs 
are reported, notify the Investigator immediately and determine whether subject should 
return to the site for an unscheduled visit. The Investigator should assess all reported AEs 
in a timely manner.
o
Interview subject regarding the Diary completion and reported events since receiving 
treatment. Remind subject to complete the Diary daily and bring it to the next on-site 
visit.
4.7.4
Visit 3, Treatment 2 (1 month (+5 weeks) after Treatment 1) - for treatment 
group only
o
Review the subject’s concomitant therapies.
o
Collect and review subject diary.
o
Interview for AEs.
o
Assess for AEs- Treating Investigator
o
Assess 
) Treating Investigator  (pre-treatment)
 
  
 
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o
Obtain Photography 2D and 3D (if receiving a treatment at this visit, perform prior to 
treatment)
o
Perform Visual Function Assessments for all subjects (if receiving a treatment at this 
visit, perform prior to treatment).
o
Perform safety assessments: Cheek sensation, Cheek firmness, symmetry and function, 
Mass formation and Device Palpability.  
o
GAIS: Perform GAIS assessment (if receiving a treatment at this visit, perform prior to 
treatment) - Investigator and Subject. 
o
Instruct the subject to complete the Subject satisfaction questionnaire (pre-treatment).
o
Instruct the subject to complete Face-Q assessment.
o
Assess whether optimal treatment result has been obtained (as agreed by the Treating 
Investigator and Subject).
o
If a second treatment is to be performed, confirm eligibility criteria 
o
No treatment should be given in the subject has a disease or condition described 
in the exclusion criteria, or an ongoing treatment related AE that in the opinion of 
the Treating Investigator would be worsened by a treatment.
For subjects who receive a second treatment: 
o
Prior to any treatment being provided, perform UPT for all females of childbearing 
potential.  The test result must be negative for a subject to receive treatment.  
o
Administer Sculptra Aesthetic. 
o
Evaluate for device deficiencies.
o
30 minutes following injection, perform Visual Function Assessments.
o
Dispense new subject diary and instruct subject on daily diary completion.  Remind 
subject to bring the diary to the next on-site visit.
o
Evaluate the subject for post-treatment AEs- Treating Investigator.
o
Schedule the next follow up visit (1 month +5 weeks) after treatment 2 visit 
4.7.5
Visit 3a, Follow up 72 hour telephone call (±24 hours) - for treatment group 
only, subjects who received a second treatment.
o
Interview subject regarding any concomitant therapies
o
Interview subject regarding any AEs that have occurred since receiving treatment. If AEs 
are reported, notify the Investigator immediately and determine whether subject should 
return to the site for an unscheduled visit. The Investigator should assess all reported AEs 
in a timely manner.
o
Interview subject regarding the Diary completion and reported events since receiving 
treatment. Remind subject to complete the Diary daily and bring it to the next on-site 
visit.
4.7.6
Visit 4, Treatment 3 (1 month (+5 weeks) after Treatment 2) - for treatment 
group only
o
Review the subject’s concomitant therapies.
 
  
 
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o
Collect and review subject diary (only applicable for subjects who received a treatment at 
Treatment 2 visit).
o
Interview for AEs.
o
Assess for AEs- Treating Investigator
o
Assess 
 Treating Investigator  (if receiving a treatment at this 
visit, perform prior to treatment) 
o
Obtain Photography 2D and 3D (if receiving a treatment at this visit, perform prior to 
treatment)
o
Perform Visual Function Assessments for all subjects (if receiving a treatment at this 
visit, perform prior to treatment).
o
Perform safety assessments: Cheek sensation, Cheek firmness, symmetry and function, 
Mass formation and Device Palpability. 
o
GAIS: Perform GAIS assessment (if receiving a treatment at this visit, perform prior to 
treatment) - Investigator and Subject. 
o
Instruct the subject to complete the Subject satisfaction questionnaire (pre-treatment).
o
Instruct the subject to complete Face-Q assessment.
o
Assess whether optimal treatment result has been obtained (as agreed by the Treating 
Investigator and Subject).
o
If a third treatment is to be performed, confirm eligibility criteria 
o
No treatment should be given in the subject has a disease or condition described 
in the exclusion criteria, or an ongoing treatment related AE that in the opinion of 
the Treating Investigator would be worsened by a treatment.
For subjects who receive a third treatment: 
o
Prior to any treatment being provided, perform UPT for all females of childbearing 
potential.  The test result must be negative for a subject to receive treatment.  
o
Administer Sculptra Aesthetic. 
o
Evaluate for device deficiencies. 
o
30 minutes following injection, perform Visual function Assessments.
o
Dispense new subject diary and instruct subject on daily diary completion.  Remind 
subject to bring the diary to the next on-site visit.
o
Evaluate the subject for post-treatment AEs- Treating Investigator.
o
Schedule the next follow up visit (1 month +5 weeks) after treatment 3 visit 
4.7.7
Visit 4a, Follow up 72 hour telephone call (±24 hours) - for treatment group 
only, subjects who received a third treatment.
o
Interview subject regarding any concomitant therapies
o
Interview subject regarding any AEs that have occurred since receiving treatment. If AEs 
are reported, notify the Investigator immediately and determine whether subject should 
return to the site for an unscheduled visit. The Investigator should assess all reported AEs 
in a timely manner.
 
  
 
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o
Interview subject regarding the Diary completion and reported events since receiving 
treatment. Remind subject to complete the Diary daily and bring it to the next on-site 
visit.
4.7.8
Visit 5, Treatment 4 (1 month (+5 weeks) after Treatment 3) - for treatment 
group only
o
Review the subject’s concomitant therapies.
o
Collect and review subject diary (only applicable for subjects who received a treatment at 
Treatment 3 visit).
o
Interview for AEs.
o
Assess for AEs- Treating Investigator
o
Assess 
 Treating Investigator  (if receiving a treatment at this 
visit, perform prior to treatment) 
o
Obtain Photography 2D and 3D (if receiving a treatment at this visit, perform prior to 
treatment)
o
Perform Visual Function Assessments for all subjects (if receiving a treatment at this 
visit, perform prior to treatment).
o
Perform safety assessments: Cheek sensation, Cheek firmness, symmetry and function, 
Mass formation and Device Palpability (if receiving a treatment at this visit, perform prior 
to treatment). 
o
GAIS: Perform GAIS assessment (if receiving a treatment at this visit, perform prior to 
treatment) - Investigator and Subject. 
o
Instruct the subject to complete the Subject satisfaction questionnaire (pre-treatment).
o
Instruct the subject to complete Face-Q assessment.
o
Assess whether optimal treatment result has been obtained (as agreed by the Treating 
Investigator and Subject).
o
If a fourth treatment is to be performed, confirm eligibility criteria 
o
No treatment should be given in the subject has a disease or condition described 
in the exclusion criteria, or an ongoing treatment related AE that in the opinion of 
the Treating Investigator would be worsened by a treatment.
For subjects who receive a fourth treatment: 
o
Prior to any treatment being provided, perform UPT for all females of childbearing 
potential.  The test result must be negative for a subject to receive treatment.  
o
Administer Sculptra Aesthetic. 
o
Evaluate for device deficiencies. 
o
30 minutes following injection, perform Visual function Assessments.
o
Dispense new subject diary and instruct subject on daily diary completion.  Remind 
subject to bring the diary to the next on-site visit.
o
Evaluate the subject for post-treatment AEs- Treating Investigator.
o
Schedule the next follow up visit month 7 (+ 2 weeks) after baseline
 
  
 
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4.7.9
Visit 5a, Follow up 72 hour telephone call (±24 hours) - for treatment group 
only, subjects who received a fourth treatment.
o
Interview subject regarding any concomitant therapies
o
Interview subject regarding any AEs that have occurred since receiving treatment. If AEs 
are reported, notify the Investigator immediately and determine whether subject should 
return to the site for an unscheduled visit. The Investigator should assess all reported AEs 
in a timely manner.
o
Interview subject regarding the Diary completion and reported events since receiving 
treatment. Remind subject to complete the Diary daily and bring it to the next on-site 
visit.
4.7.10 Visits 6, 7 and 8, Follow-up month 7 (+ 2weeks), 9 (±2 weeks), 12 (±2 weeks)
all subjects
o
Obtain weight measured at clinic.
o
Review the subject’s concomitant therapies.
o
Collect and review subject diary (only applicable for subjects in the treatment group who 
received a treatment at Treatment 4 visit).
o
Obtain 2D and 3D Photographs.
o
Perform ultrasound (at selected sites).
o
Interview for AEs
o
Perform safety assessments: Cheek sensation, Cheek firmness, symmetry and function, 
Mass formation and Device Palpability (treatment group only for device palpability). 
o
Perform Visual function assessments: Snellen visual acuity test, Extraocular muscle 
function test and Confrontation visual field 
o
Assess for AEs- Treating Investigator
o
Assess GAIS - Investigator and subject.
o
 assessment – Blinded 
Evaluator.
o
Radiance, skin tightness and jawline contour: Perform radiance, skin tightness and 
jawline contour assessment – Treating Investigator.
o
Instruct the subject to complete the Subject satisfaction questionnaire (treatment group 
only).
o
Instruct the subject to complete Face-Q assessment.
4.7.11 Unscheduled Visits
o
When necessary, unscheduled visits could take place (in particular because of an AE needing 
a specific treatment)
o
Unscheduled visits related to the study should be documented and all adverse events captured.  
 
  
 
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5
Subjects
5.1
Subject information and informed consent
The PI or his/her authorized designee must always use the IRB-approved subject information and 
informed consent form and it must not be changed without prior discussion with the Sponsor and 
approval from the applicable IRB.
It is the responsibility of the PI or his/her authorized designee to give each subject prior to inclusion in 
the study, full and adequate verbal and written information regarding all aspects of the clinical study
that are relevant to the subject’s decision to participate throughout the study, e.g. explain the purpose 
and procedures of the study, the duration and number of expected participants, possible risks 
involved, and the opinion of the IRB. The subject shall be informed that the participation is 
confidential and voluntary and that the subject has the right to withdraw from the study at any time, 
without any consequences to his/her future medical care, treatment or benefits to which the subject is 
otherwise entitled. The information shall be provided in a language clearly and fully understandable
to the subject. The subject shall be given sufficient time to read and understand the informed 
consent form and to consider participation in the study. Before any study-related activities are 
performed, the informed consent form shall be personally signed and dated by the subject and the PI 
or his/her authorized designee responsible for conducting the informed consent process. The consent 
includes information that data will be collected, recorded, processed, and may be transferred to other
countries. The data will not contain any information that can be used to identify any subject.
Photographs collected during the study will be analyzed and stored in a database by the Sponsor and 
its representatives in order to evaluate the effect of the treatment in the study. The subjects will be 
recognizable on the photographs, but their names will not be disclosed.
All original signed informed consent forms shall be filed in the Investigator file. The subject shall be 
provided with a copy of the signed and dated informed consent form and any other written 
information.
The Investigator shall ensure that important new information is provided to new and existing subjects 
throughout the study.
5.2
Inclusion criteria
The subjects must meet the following criteria to be eligible for the study:
1.
Subjects willing to comply with the requirements of the study and providing a signed written 
informed consent. 
2.
Women or men over 21 years of age.
3.
Intent to undergo correction of cheek wrinkles on both sides of the face and a 
 
 of Moderate or Severe on EACH side of the 
face, as assessed on Day 1 by the Blinded Evaluator as well as the Treating Investigator, but 
agreement on score is not required. The 
 score for each side of the face does 
not need to be equal; however, the difference between the two sides should be limited to 1 
grade.
4.
Female subjects must be postmenopausal for at least 1 year; if the subject is a female of 
childbearing potential, she agrees to use an acceptable form of effective birth control for the 
duration of the study and is willing to take a urine pregnancy test at the screening visit and 
prior to all injection visits. Acceptable forms of effective birth control methods include:
a.
Combined oral contraceptives (estrogens and progesterone) or implanted or injectable 
contraceptives with a stable dose for at least 28 days prior to the Baseline visit
b.
Hormonal or copper intrauterine device (IUD) inserted at least 28 days prior to the 
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c.
Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical 
caps) with spermicidal foam/gel/film/cream/suppository
d.
Bilateral tubal ligation prior to the Baseline visit 
e.
Vasectomized partner (in monogamous relationships) for at least 3 months prior to 
the Baseline visit 
f.
Strict abstinence (at least one month prior to baseline and agrees to continue for the 
duration of the study or use acceptable form of birth control).
5.3
Exclusion criteria
The presence of any of the following exclusion criteria will exclude a subject from enrollment in the 
study:
1.
Known/previous allergy or hypersensitivity to any of the Sculptra Aesthetic constituents.
2.
Known/previous allergy or hypersensitivity to lidocaine and other local anesthetics, e.g. amide-
type anesthetics or topical anesthetics agents.
3.
Previous or present multiple allergies or severe allergies, such as manifested by anaphylaxis or 
angioedema, or family history of these conditions.
4.
Previous tissue augmenting therapy, contouring or revitalization treatment in the face, except 
the lips, with any of the following filler prior to Baseline visit:
a.
Collagen, Hyaluronic Acid – 12 months
b.
Calcium Hydroxyapatite (CaHa), Poly L- Lactic Acid (PLLA) or permanent (non-
biodegradable)- Prohibited
5.
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, e.g.: 
a.
Resurfacing (laser, photomodulation, light, radiofrequency, ultrasound, chemical peel,
dermabrasion, or other ablative/non- ablative procedures)
b.
Needling or mesotherapy 
c.
Cryotherapy
d.
Neurotoxin injections
e.
Lipolytic injections (e.g. dexycholic acid or other lipolytic substances)
f.
Dental work, such as root canals or sinus surgery 
or is planning to undergo any of these procedures affecting the treatment area, at any time during 
the study.
6.
Presence of any disease or lesions near or on the area to be treated, e.g.
a.
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b.
Facial psoriasis, eczema, acne, rosacea, perioral dermatitis, herpes zoster/ herpes 
simplex and acanthosis
c.
Scars or deformities
d.
Cancer or precancerous condition (e.g. actinic keratosis or actinic cheilitis)
7.
History of severe elastosis and/or excessive sun exposure that in the opinion of the Treating 
Investigator, could affect the safety and effectiveness outcome of the study.
8.
History of bleeding disorders or treatment with anticoagulants or inhibitors of platelet 
aggregation (e.g. aspirin or other NSAIDs), Omega-3, or vitamin E within 14 days before 
treatment. Omega 3 and Vitamin E are acceptable only as part of a standard multivitamin 
formulation.
9.
Treatment with chemotherapy, immunosuppressive agents (inhaled corticosteroids allowed), 
immunomodulatory therapy (e.g. monoclonal antibodies or antiviral treatment for HIV or 
Hepatitis C) within 6 months before treatment. 
10. Use of topical corticosteroids or topical prescription retinoids (in the treatment area) within 1 
month of the Baseline visit or systemic retinoid treatment within 6 months of the Baseline visit.
11. Previous surgery including plastic surgery, lifting threads, tissue grafting or tissue 
augmentation with permanent implants, silicone or fat, or tattoo, affecting the treatment area.
12. History of cancer or previous radiation near or on the area to be treated.
13. HIV positive or active hepatitis.
14. History of or active collagen diseases such as systemic lupus erythematosus, rheumatic arthritis, 
polymyositis, dermatomyositis, skin or systemic scleroderma.
15. Tendency to form keloids, hypertrophic scars, or any other healing disorder.
16. Presence of piercing, beard or facial hair that could interfere with study evaluation.
17. Abnormal result on functionality, sensation, symmetry, mass formation or palpation 
assessments in the treatment area. 
18. Abnormal result on extraocular muscle function test or confrontational visual field assessment.
19. Presence of a dental, oral, or facial condition which, in the Treating Investigator’s opinion, 
would interfere with the study injections and/or study assessment, e.g. has dentures or any 
device covering all or part of the upper palate, and/or severe malocclusion or dentofacial or 
maxillofacial deformities.
20. Woman who is pregnant (confirmed by positive urine pregnancy test/serum pregnancy test), 
breast-feeding or intend to become pregnant over the duration of the study.
21. Any medical condition that, in the opinion of the Treating Investigator, would make the subject 
unsuitable for inclusion (e.g. a chronic, relapsing or hereditary disease that may interfere with 
the outcome of the study).
22. Other condition preventing the subject from entering the study in the Treating Investigator’s 
opinion, e.g. subjects failing baseline safety assessments, subjects not likely to avoid other 
 
  
 
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cosmetic treatments in the treatment area, subjects anticipated to be unavailable or incapable of 
understanding the study assessments or having unrealistic expectations of the treatment result.
23. Study site personnel, close relatives of the study site personnel (e.g. parents, children, siblings, 
or spouse), or employees and close relatives of employees at the Sponsor company.
24. Participation in any interventional clinical study within 30 days of screening.
5.4
Subject number
Prior to any study procedures being conducted, the subject must sign the informed consent form. Each 
subject who has signed the informed consent form will be assigned a screening number. Upon 
randomization, each subject will be assigned a subject numbers that will be allocated in ascending 
order within each center. A screen failure is a subject who signed the informed consent but never 
enrolled (i.e. was randomized and/or received treatment) in the study. For screen failures, the subject 
source documents should indicate which assessments have been made and the reason why the subject 
was determined to be a screen failure. A screen failure should not be re-entered in the study.
For the duration of the clinical study, each subject will be identified using the subject number for all 
documentation and discussion.
5.5
Withdrawal of subjects
Each subject should be advised in the ICF that the subject has the right to withdraw from the study at 
any time, for any reason, without prejudice.  Subjects may also be discontinued from this study if the 
investigator determines that it is in the subject’s best interest to do so, and may be withdrawn at the 
investigator discretion at any time.  
The withdrawal criteria are:

Medical Reasons
If the subject suffers from a medical condition and/or adverse events 
that, in the judgment of the Investigator makes it medically necessary to 
withdraw the subject. The specific rationale for Investigator-initiated 
withdrawal of a subject for medical reasons should document the 
specific condition for withdrawing the subject.

Withdrawal by 
Subject:
Includes consent withdrawal, subject relocation, schedule conflicts. A 
subject can withdraw their consent to participate in the study at their own 
request or be withdrawn from participation in the study at the request of 
their legally authorized representative at any time for any reason.

Lost to follow-up:
If a subject does not return for a scheduled visit, reasonable effort shall 
be made to contact that subject, confirm with three documented phone 
calls and a certified letter (delivery receipt requested) without answer 
before declaring the subject lost to follow-up.

Other:
This category is to be used for a subject who discontinues due to a 
reason other than as specified in the pre-defined categories above. 
Explain the reason for discontinuation.
The reason and date for withdrawal should be documented in the subject’s source document sand 
eCRFs.  When possible, an explanatory comment should be added to further explain the reason for 
the withdrawal.  If withdrawal of a subject occurs during a regular study visit, the eCRF for that 
specific visit shall be completed as far as possible.  
If withdrawal of a subject occurs between regular study visits, the subject should when possible 
(irrespective of the reason for withdrawal) be scheduled for a termination visit to document subject 
 
  
 
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outcome for the secondary endpoints.
If a subject is withdrawn from the study, all data collected until the time of withdrawal will be used 
in the analyses. Subjects who receive product and are withdrawn or discontinued from the study will 
not be replaced. For AEs still ongoing at the time of withdrawal, see section 8.6.11.
6
Study Products
The term “study product” refers to Sculptra Aesthetic. The study product will be provided by sponsor.
6.1
Investigational product
Sculptra Aesthetic is a poly-L-lactic acid implant in the form of a sterile non-pyrogenic suspension, 
which is reconstituted from a sterile dry powder by the addition of sterile water for injection. The 
suspension contains microparticles of poly-L-lactic acid. Poly-L-lactic acid is a biocompatible, 
biodegradable, synthetic polymer from the alpha-hydroxy-acid family. 
Sculptra Aesthetic is available in a glass vial and is to be reconstituted prior to use by the addition of 
8 mL SWFI to form a sterile non-pyrogenic suspension. 1 mL of 2% Lidocaine Hydrochloride (HCl)
is to be added immediately prior to injection. 
Each vial of Sculptra Aesthetic contains:
o
Poly-L-lactic acid 150 mg
o
Sodium carboxymethylcellulose 90 mg
o
Non-pyrogenic mannitol 127.5 mg
Investigational Study Product
Trade Name or Equivalent
Sculptra Aesthetic
Treatment Substance
Poly-L-lactic acid (PLLA)
Concentration
367.5 mg
Packaging
Single use vial
Storage Conditions
Store at room temperature, up to 30°C (86°F).  DO NOT
FREEZE. Refrigeration is not required.
Upon reconstitution, Sculptra Aesthetic can be stored for up 
to 72 hours at temperatures between 5- 30°C.
Reconstitution Volume
8 mL SWFI
Additional Anesthetic
1 mL of Lidocaine Hydrochloride 2% added to vial 
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Recommended Maximum 
Volume per treatment 
session
o
Maximum of 18 mL (2 vials) of Sculptra Aesthetic will 
be administered per treatment session
o
Maximum of 9 mL (1 vial) per cheek, evenly 
distributed within the treatment area.
Frequency intervals
Four (4) injection sessions with 1-month (+5 weeks).
Reconstitution needle size
18G
Injection needle size
25G
Mixing Instructions 
Immediate use after mix
Injection Technique
Bolus, fanning, cross-hatching, linear threading injection 
technique or other techniques at the discretion of the Treating 
Investigator
Injection Depth
Subdermal regions
Treatment Area
Within the following borders:
 Superior border - from top of tragus to top of alar crease
 Medial border - from top of the alar crease, along the 
nasolabial fold (NLF) to the inferior border of the mandibular 
ramus
 Inferior border - from medial border at mandibular ramus to 
angle of mandibular ramus
 Lateral border - from angle of mandibular ramus to top of 
tragus
6.2
Reference product
Not applicable.
6.3
Additional products and materials
The following will be supplied by the study sites:

18 G sterile needles (for reconstitution)

25 G sterile needles (for injection)

2% Lidocaine HCl. (Only the 3 Lidocaine products listed below should be used and only for 
the treatment group).
o
2% Lidocaine HCl- Hospira with 0.1% Methyl paraben
o
2% Lidocaine HCl- West Ward with 0.1% Methyl paraben
o
2% Lidocaine HCl- West Ward without preservatives

Sterile Water for Injection (SWFI), United States Pharmacopeia (USP)
 
  
 
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
Single use 5 mL sterile syringes

Single use 1 mL or 3 mL sterile syringes

Antiseptic (such as alcohol)
Topical or local anesthesia may be used at the discretion of the Treating Investigator before the 
treatment. If used, the anesthesia shall be supplied by the study site. Type of anesthesia, 
administration route, product name, and quantity used must be recorded in the eCRF.
6.4
Packaging, labelling, and storage
6.4.1
Investigational product
Sculptra Aesthetic is supplied as a sterile freeze-dried preparation for injection in a clearglass vial, 
which is sealed by a penetrable stopper, covered by an aluminum seal with a flip-off cap. Each 
carton of Sculptra Aesthetic contains one vial of poly-L-lactic acid, sodium carboxymethylcellulose, 
non-pyrogenic mannitol.
Each vial of Sculptra Aesthetic is packaged for single-use only. 
Labelling will be performed according to United States Code of Federal Regulations (CFR) 21 CFR 
812.5: Labelling of investigational devices. The carton will be labelled with lot number, expiration 
date, CTN number, and the following:
“CAUTION – Investigational Device. Limited by Federal Law to Investigational Use.”
Sculptra Aesthetic can be stored at room temperature, up to 30ºC (86ºF). Upon reconstitution, 
Sculptra Aesthetic can be stored for up to 72 hours at temperatures between 5-30°C. DO NOT 
FREEZE.  Refrigeration is not required.
Detailed product information is provided in the study IFU.   
6.4.2
Reference product
No treatment control, i.e. reference product is not applicable. 
6.4.3
Product accountability
The study product will be released to the Investigator or his/her authorized designee after study 
approvals have been received from the FDA and IRB and the CTA has been signed by all parties.
The Investigator must ensure that the study products are kept in a secure location, withaccess limited 
to those authorized by the Investigator.
The study products must be traceable from the manufacturer to their use in subjects until return or 
disposal. It is therefore important that the Investigator maintains accurateproduct accountability 
records, i.e. documentation of the physical location of all investigational products, deliveries, and 
return of investigational products between the Sponsor and the Investigator, and documentation of 
administration of product to the subject.
When the study is completed, all unused or expired investigational product at each studysite shall be 
returned to the Sponsor representative for destruction, or be destroyed locally atthe site if 
documented as agreed with Sponsor.
Any malfunctioning investigational products shall be reported as described in Section 8.7.3. 
Products deliberately or accidentally destroyed during shipment or at a study site shallbe accounted 
for and documented. Used vials, syringes, needles, and any unused material must be discarded 
immediately after the treatment session and must not be reused due to risk for contamination of the 
unused material and the associated risks including infections according to standard procedures at the 
site. Disposal of hazardous material, i.e. syringes and needles must conform to applicable laws and
 
  
 
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regulations.
The study products must not be used outside of the study.
All study products sent to the Investigator will be accounted for and no unauthorized use is 
permitted.
6.5
Treatment
6.5.1
Treatment procedure 
The investigational product is reserved for use by Treating Investigators who areexperienced in 
treating cheek wrinkles.  
Before treatment, the subject will be informed about the expected post-treatment events that should 
be recorded in the subject diary and potential risks involved with the treatment and when to contact 
the Investigator in case of emerging symptoms.
The investigational product is reserved for use by doctors trained in the appropriate injection 
technique. Injection procedures are associated with a risk of infection. Aseptic technique and
standard practice to prevent cross-infections should be observed at all times including the use of 
disposable gloves during the injection procedure. All traces of make-up in the treatment area should 
be removed prior to any injection. The treatment site should be cleaned with a suitable antiseptic
solution.
An ice pack can be applied on the site for a short period. Topical or local injection anesthesia may be 
used to further reduce pain on injection. If (topical or local) anesthetic or ice is used, the area should 
be cleaned after anesthetic is removed. The use of anesthetic or ice should be recorded in the source 
documentation and on the eCRFs.
Sculptra Aesthetic (sterile, freeze-dried, injectable poly-L-lactic acid) is available in 367.5 mg dose 
vials and will be reconstituted prior to use by the addition of 8 ml of SWFI at the investigational site 
following the reconstitution instructions in the study IFU.
Immediately prior to injection, 1 mL of 2% lidocaine shall be added to make a total volume of 9 mL 
and the vial should be shaken
For intravascular complications or embolic events, the treating physician should provide prompt 
medical attention and follow relevant clinical practice guidelines (8) for handling these symptoms. 
The treating physician should also review the Intravascular Treatment Protocol provided separately as 
a supportive tool.
Sculptra Aesthetic will be administered using a 25G needle. Injections will be made subdermally, i.e. 
in the subcutaneous and supraperiosteal region. A maximum of 18 mL (2 vials) of Sculptra Aesthetic
will be administered per treatment session with a maximum of 9 mL (1 vial) per cheek, evenly 
distributed within the treatment area. 
In this study, the study products will be administered in the Treatment area defined within the 
following anatomical borders:
 Superior border - from top of tragus to top of alar crease
 Medial border - from top of the alar crease, along the NLF to the inferior border of the 
mandibular ramus
 Inferior border - from medial border at mandibular ramus to angle of mandibular ramus
 Lateral border - from angle of mandibular ramus to top of tragus
 
  
 
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Injection technique
The injection technique is important for the aesthetic effect of the treatment. It is recommended to use 
a standard injection technique for all subjects per site to limit variability due to technique. Before 
product is injected, aspiration should be done to avoid intravascular injection.
The injection technique is at the discretion of the investigator, proposed techniques are:

Antegrade linear threading: also called push-ahead technique as some product is pushed ahead 
of the needle. Once the needle is in place, the product is injected ahead while inserting the 
needle in the tissue.

Retrograde linear threading: the needle is threaded into the tissue at the appropriate depth, and 
the product in injected as a straight line on withdrawal of the needle

Bolus: multiple aliquot injections of the product is injected along a line or regions of the 
tissues

Fanning: a number of linear threads to spread the product over a wider area

Cross-hatching: combines multiple injections of linear threading that crisscross at right angle to 
provide volume in a square shape
6.5.2
Treatment regimen (dose and interval)
Eligible subjects randomized to the treatment group will receive a single regimen of Sculptra 
Aesthetic. A single regimen consists of up to 4 injection sessions with 1-month (+5 weeks) intervals. 
The first treatment will be administered on Day 1/ Baseline visit. Sufficient amount of study product, 
as determined by the Treating Investigator, should be injected to achieve optimal correction:
 Optimal correction is defined as at least a one-step improvement on the 
 
t and the best correction that can be achieved as agreed by 
Treating Investigator and subject.
 Three additional treatment sessions may be performed if needed to achieve optimal 
correction, as determined by the Treating Investigator and subject.
Treatment will stop when optimal correction has been achieved and subsequent visits will be follow-
up visits. Treatment will not be performed if the subject has a disease or condition described in the 
exclusion criteria, or an ongoing treatment-related AE that in the opinion of the Treating Investigator 
would be worsened by a treatment.
6.5.3
Post-treatment care
The subject should avoid excessive sun, UV lamp exposure and extreme temperature until any initial 
swelling and redness has resolved.
The subject should be asked to avoid touching or shaving the treated area and not to apply any creams 
or cosmetics in the treated area before the skin has healed completely in order to prevent infections or 
elicit an inflammatory reaction. The subject should also be reminded to abstain from prohibited 
medications, treatments, and procedures.
A subject diary will be handed out after each treatment session, and the subject should be reminded to 
record all expected symptoms in the treated area.
Detailed information regarding the post-treatment care and patient instruction is provided in the study 
IFU. 
6.5.4
Post-trial provisions
In time, the implant will be degraded in the body and additional treatments will benecessary to 
maintain the aesthetic result. 
 
  
 
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6.5.5
Treatment compliance
The treatment will be administered by the Treating Investigator at the investigationalsite and be 
recorded in the eCRF.
7
Effectiveness Assessments
The methods for collecting effectiveness data are described in this section. To minimize inter-
observer variability, every effort should be made to ensure that preferablythe same individual who 
made the initial baseline assessments complete all corresponding follow-up evaluations.
The methods for collecting effectiveness data are:
o
 
o
Photography 2D and 3D
o
GAIS 
o
Subject Satisfaction Questionnaire, 
o
FACE-Q “Satisfaction with Cheeks”
o
Return to social engagement after treatment recording
o
Ultrasound
o
Radiance, skin tightness and jawline contour assessment. 
In addition, a Central Independent Photographic Reviewer will assess photographs. 
 
  
 
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7.3
Global Aesthetic Improvement Scale (GAIS)
The 7-graded GAIS will be used to live assess the aesthetic improvement of cheek wrinkles by the 
Treating Investigator and the subject, by comparing to a photograph taken at the baseline visit before 
the first treatment. The Treating Investigator and the subject will, independently of each other, 
respond to the question: “How would you describe the aesthetic improvement today compared to the 
photograph taken before treatment?” by using the respective categorical scale below.
 
  
 
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Information on AEs can also be obtained from signs and symptoms detected during each examination 
by the Investigator or designee, which should include visual inspection of the treatment area.
AEs must be documented in the source document and eCRF without regard for cause or relation to 
investigational product. Events that occur after Screening but prior to randomization should be 
recorded in the subject’s medical history. 
If in the process of the interview, additional information regarding medical history or pre-planned 
medical or surgical procedures is revealed, it must be documented in the source document(s) and the 
eCRF.
It is the responsibility of the Treating Investigator to determine severity of the AE and relatedness of 
the event to the study product and/or injection procedures.  Adverse Events must be reported as 
outlined below in section 8.6. 
8.1
Assessment of AEs by direct questioning to subject and evaluation of subject
Each subject should be questioned about AEs at each visit following randomization and/or treatment.
Definition and Reporting requirements are found in section 8.6. 
8.2
Subject Diary Data
A subject diary will be dispensed to all subjects for daily completion for 28 days beginning on 
injection day for each treatment with direct questioning for pain, tenderness, redness, bruising, 
swelling, itching, lumps/bumps and “other”. 
The subject will also be specifically instructed to record presence of any of the following symptoms in 
the “other” section; Changes in vision (i.e. loss of vision, blurriness, double vision, pain in or around 
your eye, blindness, blind spots, problems moving your eyes), Skin changing color around the eyelids, 
Crusty or scabby skin around the eyelids, Pain, Headache, Fever, Dizziness, Confusion, Weakness or 
numbness in the arms or legs, Changes to consciousness or alertness, Difficulty speaking/ speech 
impairment or Face droop. The diary will include specific instructions to seek immediate medical 
attention if any of these symptoms or signs are observed.
Diary data will be counted and displayed separately from other AE data.
8.3
Laboratory assessments
For all women of childbearing potential, including those currently using contraception, a urine 
pregnancy test will be performed at screening and all injection visits (prior to treatment). The test 
result must be negative for the subject to receive anytreatment with study product.  The test result 
will be documented in source data andthe eCRF.
8.4
Visual Function assessments
Visual function assessments will be performed for all subjects. For subjects in the treatment group, the 
assessments will be performed both prior to and post injection of the study product at baseline and all 
scheduled treatment visits. The post-treatment assessments should be performed 30 min after the 
injections are completed. In the event of blindness or any significant ophthalmic sign or symptom, 
 
  
 
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subjects are to undergo immediate evaluation by an ophthalmologist or a retina specialist. All incidences 
of visual disturbances, regardless of relationship to study product or seriousness, are considered 
Adverse Events of Special Interest (AESIs) and include but are not limited to the following: any loss of 
vision, blurry vision, double vision, pain in or around the eye, blind spot or shadow in the visual field, 
trouble moving eyes. AESI’s should be reported (using the Adverse Event Clarification Form) within 
24 hours of awareness. Please refer to recording instructions in section 8.6.6.
8.4.1
Snellen visual acuity test 
A Snellen Eye Chart will be used to assess visual acuity for distance vision.  Visual Acuity will be 
conducted using the subject’s best distance correction (e.g. with contacts or spectacles) at a distance of 
6 feet from the chart.  Each eye will be measured separately by either using an occluder or having the 
subject cover one eye at a time.  The subject will be asked to start reading the letters at the top of the 
chart working their way to the bottom.  The smallest row of letters that the subject can read will indicate 
their visual acuity listed on the chart.  Snellen Visual Acuity will be recorded in their source 
documentation and eCRF.  If there are two or more visual acuity line changes during the course of 
study, these should be reviewed and assessed by the Investigator for a potential adverse event.
8.4.2
Extraocular muscle function test
Extraocular muscle function testing examines the function of the eye muscles.  This test observes the 
movement of the eyes in six specific directions to evaluate weakness or other problems in the 
extraocular muscles.  The subject will be asked to sit or stand with their head up and looking straight 
ahead.  The assessor will hold a pen or other object approximately 16 inches in front of the subject’s 
face.  The assessor will then move the object in several directions and ask the subject to follow it with 
their eyes, without moving their head.  Normal or Abnormal will be recorded in the source 
documentation and eCRF.  Changes in movement of the eyes during the course of the study should be 
reviewed and assessed by the Investigator for a potential adverse event.
8.4.3
Confrontation visual field
The Confrontation Visual Field test will be used to assess the subject’s peripheral vision.  The 
examiner will sit facing the subject, about 3 to 4 feet away from the subject and ask the subject to fix 
their gaze on the examiner’s eye.  The examiner will hold their arms straight out to the side and bring 
their hands into the subject’s visual field from the sides in each quadrant.  The subject will signal as 
soon as the hand is seen.  Results will be recorded as normal or abnormal in the source documentation 
and eCRF.  Changes in the visual field of the eyes during the course of the study should be reviewed 
and assessed by the Investigator for a potential adverse event.
8.5
Other safety assessments
At all physical visits, a study staff member who is qualified by training and experience to perform 
safety assessments, will assess each subject’s cheek sensation; firmness and symmetry; and mass 
formation. After treatment with the study product, product palpability will be performed at each 
physical visit.
8.5.1
Cheek sensation 
Cheek sensation will be tested at all physical study visits using two methods:
1) Monofilament test - assessing the subject’s ability to feel the sensation of a 0.4G monofilament 
on 3 points on right and left cheek and
2) Cotton Wisp test - assessing the subject’s ability to feel the sensation of a cotton wisp on 3 
points on the right and left cheek. The 3 different points on each side will be tested randomly. 
 
  
 
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Subjects will be blindfolded and asked to acknowledge sensation or lack of sensation at each 
point. Any lack of sensation should be further assessed by the Investigator for confirmation of any 
potential adverse event. 
. 
8.5.2
Cheek firmness, symmetry and function
At all physical visits, a study staff member who is qualified by training and experience to perform 
safety assessments will assess each subject’s cheek firmness, symmetry (with face at rest and with 
eyes tightly closed), and function (puff cheeks, broad smile, and chewing motion). These parameters 
will be rated as “Normal” or “Abnormal.” Any abnormal result should be further assessed by the 
Investigator for confirmation of any potential adverse event.  
8.5.3
Mass formation
Mass formation in the cheeks will be assessed by a study staff member that is qualified by training and 
experience to perform safety assessments at screening/baseline and at all physical visits. Mass formation 
will be defined as lumps or aggregation of coherent material. An assessment of mass formation is to be 
recorded as an adverse event.
8.5.4
Device palpability- only for subjects in the treatment group
Device palpability will be assessed at each scheduled post-treatment visit and will assess whether or 
not the palpability is the normal expected feel. An unexpected feel is to be recorded as an adverse 
event.  
8.6
Adverse events
8.6.1
Definition of an adverse event
An AE is any untoward medical occurrence, unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or other persons1, whether or not related to 
the study product. 
This definition includes:
a)
events related to the investigational product or the reference product
b) events related to the procedures involved
8.6.2
Definition of a serious adverse event
A serious adverse event (SAE) is an AE that:
a)
led to death,
b) led to serious deterioration in the health of the subject, that either resulted in
1. a life-threatening2 illness or injury, or
2. a permanent impairment of a body structure or body function, or
                                                
1 For users or other persons, this definition is restricted to events related to the investigational product.
2 The term “life-threatening” in the definition of “serious” refers to an event in which the patient was at risk of 
death at the time of the event; it does not refer to an event, which hypothetically might have caused death if it 
were more severe. (Source: ICH-E2A clinical safety data management: definitions and standards for expedited 
reporting).
 
  
 
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3. in-patient or prolonged hospitalization3, or
4. medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function,
c)
led to fetal distress, fetal death, or a congenital abnormality or birth defect
In cases of doubt, whether an AE fulfils a serious criterion or not, there should be a predisposition to
report as a SAE rather than not report as such (see Section 8.6.5).
8.6.3
Definition of unanticipated adverse effect 
An unanticipated adverse device effect is any serious adverse effect on health or safety or any life-
threatening problem or death caused by, or associated with, the investigational product, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence, or any 
other unanticipated serious problem associated with a device that relates to the right, safety or welfare 
of the subject (see US requirement CFR 812.3 (s).
8.6.4
Recording instructions
Each subject with an AE occurring after enrollment through study exit should be fully recorded in the 
source document(s) for further transcription into the eCRF.  Each subject should be questioned about 
AEs at each study visit following randomization and treatment.  . The question asked should 
be:”Since your last clinical visit; have you had any health problems?” Information on AEs can also be 
obtained from signs and symptoms detected during each examination or from a laboratory test, 
observations made by the study site personnel, subject diaries, or spontaneous reports from the 
subjects or their relatives. 
When an AE is related to a device deficiency (refer to Section 8.7), including technical device 
malfunction, the AE shall be recorded on the AE form/module in the eCRF and the technical 
complaint shall be reported separately on the clinical study complaint form, provided separately in the 
investigator file, and the eCRF.
Investigators, or other study site personnel, shall record all AEs in the eCRF, including:
a)
Event term (recorded in standard medical terminology and avoiding abbreviations)
b) Affected area
c)
Start date (first day with symptoms)
d) Stop date (last day with symptoms)
e)
Intensity (mild, moderate, or severe according to definition in Section 8.6.4.1)
f)
Seriousness (serious or not serious, according to definition in Section 8.6.4.2)
g)
Causal relationship to study product or study product injection procedure (yes or no)
h) Action taken (none, medication treatment, non-pharmacological treatment, or other 
procedures/tests, subject withdrawn)
i)
Outcome of the AE (ongoing, recovered, recovered with sequelae, death, chronic/ stable, not 
recovered at the end of the study)
The pre-defined, expected post-treatment events shall be assessed separately.  These events shall be 
collected daily by subjects in a diary for up to 28 days after each treatment.  
                                                
3 Planned hospitalization for a pre-existing condition, or a procedure required by the CSP, without serious 
deterioration in health, is not considered a SAE. (Source: ISO14155:2011).
 
  
 
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8.6.4.1
Intensity
Intensity will be recorded for each reported AE. The following definitions of intensity are to be used:
Mild:
Awareness of symptoms or signs, but easily tolerated (acceptable)
Moderate:
Enough discomfort to interfere with usual activity (disturbing)
Severe:
Incapacity to work or to do usual activity (unacceptable)
If the intensity changes within one day, the maximum intensity of the AE during that day shall be 
recorded.
8.6.4.2
Causal relationship and seriousness
Each AE, serious as well as non-serious, shall be assessed by the Investigator for causal relationship 
with the study product and its use (the injection procedure) and for seriousness (Yes or No) of the 
event. 
A two-point scale (Yes or No response) shall be used for the causality assessments. The Investigators 
shall be asked to indicate a response to each of the following questions in the eCRF:

“Do you consider that there is a reasonable possibility that the event may have been caused by 
the study product?”, and 

“Do you consider that there is a reasonable possibility that the event may have been caused by 
the study product injection procedure?”
If any of these questions is answered Yes, the AE is considered related.
Each AE will also be assessed for causal relationship and seriousness by the Sponsor, in order to fulfil
regulatory requirements. 
8.6.5
Reporting of adverse events 
Adverse event reporting on each subject shall start upon enrollment (i.e. randomized and/or treated) in 
the study.  Any events that occur after the subject signs the ICF but before enrollment will be recorded 
in the subject’s medical history.  
The reporting shall continue during each follow-up visit (including telephone contacts and extra visits 
between planned visits) until the last scheduled visit in the study.
All AEs, non-serious as well as serious, are to be reported as an AE in the eCRF.
8.6.6
Reporting of adverse events of special interest (AESIs)
All incidences of visual disturbances, regardless of relationship to study product or seriousness, are 
considered Adverse Events of Special Interest (AESIs) and include but are not limited to the following: 
any loss of vision, blurry vision, double vision, pain in or around the eye, blind spot or shadow in the 
visual field, trouble moving eyes.
AESIs should be reported (using the AE Clarification Form) within 24 hours of awareness to the 
Contract Research Organization (CRO) at the email address 
 In case 
of difficulty to obtain all the required information within 24 hours, an initial report can be submitted 
with follow up information provided within 24 hours of awareness of the new information.
The following information should be provided when reporting an AESI: 
•
Subject identification (subject number and initials)
•
Event description including observed symptoms
•
Medical history related to event
 
  
 
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•
Event onset date and time
•
Depth of injection
•
Interventions implemented to treat event
•
Event outcome (with resolution date and time if applicable)
•
Relatedness to study product or procedure
•
Seriousness of event
•
Study treatment information (number of injections, date of injections, name of product
injected, batch number/lot number, volume injected, injection depth etc.)
If the Investigator assesses an AESI to be serious, an SAE report should be submitted as specified in 
Section 8.6.7. 
Upon receipt of the AESI report, the Medical Monitor and Sponsor will review the information 
provided, assess the event, and report to the RA, as applicable.  The investigator is responsible for 
reporting events to the IRB per the IRB reporting guidelines.  
8.6.7
Reporting of serious adverse events
The Investigator shall report any SAE to the CRO immediately but not later than 24 hours of 
awareness of the event. This initial report can be made via e-mail or submitted via the eCRF. 
In case of difficulty to obtain all the required information within 24 hours, an initial report can be 
submitted, with the following information as a minimum, irrespective of whether some of it is 
regarded as preliminary:

CTN 43USSA1812

Subject identification (age, gender, subject number)

Date when AE occurred

Date when AE became serious

Adverse event description

Name of investigator and original reporter (if other than Investigator)

Name of study product (investigational product or no-treatment)\

Treatment specification
Follow-up information and data missing in the initial SAE reporting shall be gathered as soon as 
possible and reported to the CRO, immediately but not later than 24 hours of awareness of the new 
data. Complete and adequate information on each SAE is required. All attempts to obtain this 
information, including dates for follow-up activities, must be documented by the Investigator.
Supporting documentation to be provided with the SAE report:

Concomitant therapies form/list

AE form/list

Medical history form/list

Any other relevant supporting documentation (e.g. hospital notes, death certificate, autopsy 
reports etc.)
E-mail for SAE reporting:
 
  
 
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The SAE form must be signed and dated by the Investigator. If the initial 24-hour SAE report does not 
contain full information or if it is made without using the SAE form the fully completed and signed 
SAE form shall be e-mailed to the CRO. A copy of the fully completed SAE form shall be kept at the 
site. The blinded evaluator should perform live effectiveness assessments only and not discuss the 
treatment or any potential adverse events with the patient. 
In addition, the PI shall report SAEs to the responsible IRB without undue delay. The PI is 
responsible for checking what reporting procedures are applicable for his/her IRB regarding SAEs and 
final report of the outcome of the study and to comply with such reporting procedures during the 
study period.
The Sponsor is responsible for reporting to the RA, if applicable and according to national 
regulations.
8.6.8
Stopping Rule
Enrollment and injections at an investigational site will be temporarily halted if an SAE occurs for a 
vascular embolic event that leads to skin necrosis, vision loss, or stroke and is determined by the 
Investigator to be directly or possibly related to the investigational device or injection procedure.  The 
SAE will be investigated by the Sponsor. 
If the Sponsor’s investigation concludes:
•
The SAE was unanticipated, directly related to the investigational product or device injection 
procedure, and presents an unreasonable risk to study subjects, enrollment and/or injections 
will be immediately suspended for all study sites until the event can be properly characterized 
and an appropriate treatment strategy is established to prevent recurrence of the unanticipated 
event.  All Investigators will be notified of the suspension.  The IRB and RA will also be 
notified.  
•
If the SAE does not meet the above criteria, then enrollment and injections in the study will 
continue.  
8.6.9
Reporting of unanticipated adverse device effects
The Investigator shall submit to the sponsor and to the reviewing IRB a report of any unanticipated 
adverse device effect occurring during the study as soon as possible, but in no event later than 10 
working days after the investigator first learns of the effect (see US requirement 21 CFR 812:150 (a.), 
for contact details, see section 8.6.7.
8.6.10 Follow-up of unresolved events ongoing at termination of the study
All serious as well as non-serious AEs with a causal relationship to the study product or treatment 
procedure and ongoing at study end, shall be followed up after the subject's participation in the study 
is over. Such events shall be followed-up after the last study visit until resolved, assessed as chronic 
or stable, or subject is lost to follow up. Follow-up information shall be reported on the AE follow-up 
form.
8.6.11 Reporting and follow-up of events occurring after subject termination of the 
study
All adverse events with a causal relationship to the study products or treatment procedure that the 
Investigator becomes aware of, serious as well as non-serious, with onset after the study termination 
(subject’s last study visit) shall be reported to the Sponsor. The report should as a minimum include 
the information described in Section 8.6.4. The report can be sent via e-mail according to contact 
details specified in Section 8.6.7.
 
  
 
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8.6.12 Pregnancy
Pregnancy itself is not regarded as an AE.
If there is a pregnancy during the study period the subject must be withdrawn from any following 
study treatment, but should continue to be followed within the study and the outcome of pregnancy 
must be reported even if the delivery occurs after study completion.
A pregnancy confirmed during the study period must be reported by the Investigator on a pregnancy 
report form immediately upon acknowledge be submitted to the Sponsor according to contact details 
specified in section 8.6.7. The report can be prospective or retrospective. Follow-up shall be 
conducted to obtain outcome information on all prospective reports. 
Cases that led to fetal distress, fetal death or a congenital abnormality or birth defect are to be 
regarded as SAEs and shall be reported on the exposure in utero report form to the Sponsor 
immediately but no later than 24 hours after the Investigators awareness. These events shall be
handled as SAEs during data processing. Other complications during the pregnancy that are related to 
the pregnant woman and fulfils any serious criteria, such as pre-eclampsia requiring hospitalization, 
shall be reported and handled as SAEs. Elective abortions without complications shall not be reported 
as AEs.
8.6.13 Anticipated adverse events
Information regarding anticipated AEs for Sculptra Aesthetic is included in the study specific IFU.(1)
8.7
Device deficiencies
8.7.1
Definition of a device deficiency
A device deficiency is defined as an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety4, or performance.
Note: Device deficiencies include malfunctions, use errors, and inadequate labelling.
8.7.2
Recording instructions
When a device deficiency is discovered, Part A of the clinical study complaint form shall be 
completed by the Investigator and the source data recorded in the eCRF. The type of complaint shall 
be described and injury to the subject or user or unintended exposure to study product shall be 
reported as applicable. If an injury has occurred, an AE or an SAE form shall be completed as 
applicable (refer to section 8). If no SAE was experienced as a result of the device deficiency, the 
Investigator shall assess whether or not the device deficiency could have led to an SAE if:

Suitable action had not been taken,

Intervention had not been made or,

Circumstances had been less fortunate
In Part B of the clinical study complaint form, the Sponsor will make the same assessment. 
8.7.3
Reporting of device deficiencies
The Investigator shall send the completed clinical study complaint form to the CRO.
E-mail for device deficiencies reporting:
                                                
4 Inadequacy of device safety refers to properties of the device which could have or have led to an AE.
 
  
 
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A device deficiency that led to a SAE and any device deficiency that could have led to a SAE shall be 
reported to the CRO within 24 hours after the Investigator’s awareness (for contact information, see 
section 8.6.7). If the form is completed within an eCRF system, refer to the eCRF completion 
guidelines.
If the Investigator or the Sponsor assesses that the device deficiency could have led to a SAE the 
Sponsor is responsible for reporting the device deficiency to RA and the PI is responsible for 
reporting it to the IRB.
The deficient study product shall be kept by the study site until the Sponsor has confirmed whether 
the product shall be returned to Sponsor for further study or if it can be destroyed at the study site.
9
Data Handling and Management 
9.1
Data management
Data management based on GCP refers to the activities defined to achieve safe routines to enter 
clinical data information into a database, efficiently and avoiding errors. The data management 
routine includes procedures for database set-up and management, data entry and verification, data 
validation, and documentation of the performed activities including information of discrepancies in 
the process. The data management process will be described in detail in the data management plan 
(DMP).
The database, the data entry screens and program will be designed in accordance with the CIP and the 
CRF template. Data validation will be performed by computerized logical checks and manual review. 
Drugs and events will be coded in accordance with World Health Organization (WHO) Drug and 
medical dictionary for regulatory activities (MedDRA) dictionaries as specified in the DMP. Safety 
data (SAE and if applicable AE of special interest) in the clinical database will be reconciled against 
the data in the safety database.
When all efforts have been made to ensure that the data recorded in the eCRFs and entered in the 
database is as correct and complete as possible, the clinical database will be locked. Study data will be 
transferred to SAS datasets, which thereafter will be write-protected. Statistical analyses will be 
generated in SAS using data from the locked datasets.
9.2
Electronic case report forms 
An electronic data capture application, compliant with regulatory requirements for software validation 
US FDA 21CFR11 will be used to collect, modify, maintain, archive, retrieve, and transmit study 
data. An eCRF is required and shall be completed electronically for each screened subject (screening 
visit) and enrolled subjects (subsequent visits). 
The eCRF includes password protection and internal quality checks, such as automatic range checks, 
to identify data that appear inconsistent, incomplete, or inaccurate. Study data shall be entered directly 
from the source documents, which are to be defined at each site before inclusion of the first subject.
Authorized study site personnel designated by the PI shall complete data collection. Appropriate 
training and security measures shall be completed with all authorized investigation site personnel 
prior to the study being initiated and any data being entered into the system for any subject.
The study data is the sole property of the Sponsor and shall not be made available in any form to third 
parties, except for authorized representatives of appropriate RA, without written permission from the 
Sponsor. At the end of the study, electronic data are kept at the Sponsor and a copy (provided by the 
vendor) at the study site as part of the Investigator file.
Any delegation of collection of data shall be specified and recorded.
 
  
 
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9.2.1
Data entry
All data shall be entered in English. The eCRFs should always reflect the latest observations on the 
subjects participating in the study. Therefore, the eCRFs shall be completed as soon as possible during 
or after the subject’s visit. The subject’s identity must always remain confidential, i.e. the name and 
address of the subjects must not be registered in the eCRFs or in the database. The Investigator must 
verify that all data entries in the eCRFs are accurate and correct. If some assessments are not done, or 
if certain information is not available, not applicable or unknown, the Investigator shall indicate this 
in the eCRF. The Investigator shall electronically sign off the study data. By signing, the Investigator 
takes responsibility for the accuracy, completeness, and legibility of the data reported to the Sponsor 
in the eCRF.
9.2.2
The query process
The monitor shall review the eCRFs and evaluate them for completeness and consistency. Each eCRF 
shall be compared with the respective source documents to ensure that there are no discrepancies 
between critical data. All entries, corrections, and alterations shall be made by the PI or his/her 
authorized designee. The monitor cannot enter data in the eCRFs. Once study data have been 
submitted to the central server via the eCRF, corrections to the data fields will be audit trailed, 
meaning that the reason for change, the name of the person who made the change, together with time 
and date will be logged. Roles and rights of the site personnel responsible for entering study data into 
the eCRF shall be determined in advance. If discrepant data is detected during review of the data, 
either by the Sponsor or by its representatives, the responsible data manager or monitor shall raise a 
query in the electronic data capture application. The query shall state the question or data to be 
changed and shall be resolved in the system by the PI or his/her authorized designee. The appropriate 
study site personnel shall answer the queries in the eCRF within a reasonable timeframe Answered 
queries will be audit trailed by the electronic data capture application meaning that the name of study 
site personnel, time, and date is logged. Answered queries will then be closed by the appropriate study 
personnel (i.e. data manager, site monitor, etc.)
9.2.3
User identification
Electronic CRF records will be automatically appended with the identification of the creator, by 
means of their unique UserID. Specified records shall be electronically signed by the Investigator to 
document his/her review of the data and acknowledgement that the data are accurate. This will be 
facilitated by means of the Investigator’s unique UserID and password; date and time stamps will be 
added automatically at time of electronic signature. If an entry in an eCRF requires change, the 
correction shall be made in accordance with the relevant software procedures. 
9.2.4
Audit trail
All changes will be fully recorded in a protected audit trail and a reason for the change shall be stated.
Once all data have been entered, verified, and validated, the database will be locked.
9.3
Source documents
Source documents are all documents used by the Investigator or hospital that relate to the subject’s 
medical history, that verifies the existence of the subject, the inclusion and exclusion criteria, and 
all records covering the subject’s participation in the study. They include laboratory notes, 
memoranda, material dispensing records, subject files,etc.
The Investigator is responsible for maintaining source documents. Source data should be 
attributable, legible, contemporaneous, original, accurate, and complete. Changes to source data 
should be traceable, should not obscure the original entry and should be explained if necessary.
Source documents shall be made available for inspection by the monitor at each monitoring visit. 
The Investigator mustsubmit a completed eCRF for each subject for whom signed informed 
consent has been collected.
 
  
 
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All supportive documentation submitted with the eCRF, such as laboratory or hospital records, shall 
be clearly identified with the CTN and subject number. Any personal information, including name, 
shall be removed or rendered illegible to preserve individual confidentiality.
9.4
Record keeping and access to source data
The PI/Institution shall permit study-related monitoring, audits, IRB review, and RA inspections and 
shall provide direct access to the source data/medical record including the identity of all participating 
subjects (sufficient information to link records, i.e. eCRF, medical records, original signed informed 
consent forms and detailed records of study product accountability). The records shall be retained by 
the PI as required by local legislation and international guidelines. Any transfer of responsibility for 
storage of the records shall be documented and the Sponsor shall be informed in writing.
The Sponsor shall verify that each subject has consented in writing to direct access to the original 
medical record/source data (by the use of written subject information and signed informed consent). 
The data recorded in the eCRFs will be checked for consistency with the source documents/medical 
record by the monitor during monitoring (source data verification; SDV). In order to be able to 
perform SDV, information about each subject’s participation in the study has to be detailed in the 
medical record or other relevant source. 
9.5
Document and data retention
All records pertaining to the conduct of the study, including signed eCRFs, informed consent forms, 
study product accountability records, source documents, and other study documentation must be 
retained for retained for as long as is specified in the CTA after study completion or longer if required 
by national legislation. Sponsor will inform the site(s) as to when these documents no longer needs to 
be retained. Measures shall be taken to prevent accidental or premature destruction of these 
documents (e.g. protection against damage and unauthorized access, preferably by storage in a 
fireproof cabinet).
After study completion and database lock, a security sealed CD with electronic study data shall be 
provided by the eCRF vendor for archiving.
It is the PI’s responsibility to inform the Sponsor in writing if the Investigator file is moved or if the 
responsibility for the documents is transferred to someone else.
10
Statistical Methods
10.1
General
A comprehensive Statistical Analysis Plan (SAP) with detailed description of all statistical analyses 
will be developed. 
All study data will be listed in subject data listings.
All statistical analyses, including summary tables and data listings, will be performed using SAS. 
Confidence intervals will be two-sided and constructed at a confidence level of 95%. Statistical tests 
will be performed at a significance level of 5%, and p-values will be two-sided.
All endpoints will be summarized descriptively. Continuous endpoints will be summarized using 
mean, median, standard deviation, minimum and maximum values, for the observed value as well as 
the change from baseline. Categorical endpoints will be presented in frequency tables with number 
and percentage of observations for each level.
 
  
 
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10.2
Analysis populations
The following populations will be defined:

Safety
Includes all subjects who were treated with Sculptra Aesthetic 
or randomized to no treatment control group. Subjects are 
analyzed based on the as treated principle (i.e. according to 
the treatment actually received).

Intention-to-treat (ITT)
Includes all subjects who were randomized based on the as 
randomized principle (i.e. according to the treatment they 
were randomized to).

Per protocol (PP)
Includes all subjects in ITT who complete the 12 month after 
baseline visit without any deviations considered to have 
substantial impact on the primary effectiveness outcome.
ITT is the primary population for all effectiveness analyses. The primary effectiveness analysis will 
be repeated using the PP analysis set if there is at least a 10% difference in the number of subjects 
between the PP and ITT sets. Safety analysis is performed based on the safety population set.
The disposition of subjects will be presented in tables and/or figures as appropriate.
10.3
Demographics, baseline assessments, and subject characteristics
Demographic endpoints, baseline assessments, and subject characteristics will be presented by 
treatment group, based on the ITT analysis set using descriptive statistics, as appropriate.
10.4
Effectiveness analysis
No adjustment to the level of significance will be done; p-values obtained for any endpoint other than 
the primary will only be provided for ease of interpretation of the results.
For responder rates based on the 
and GAIS, and percentage of improved subjects according to 
IPR, results for the right and left side of the face combined as well as separately, will be calculated.
Number and percent of subjects in each response category for 
 GAIS and IPR, will also be 
presented.
10.4.1 Primary effectiveness analysis
The null hypothesis will be that there is no relationship between responder rate and treatment. The 
alternative hypothesis will be that there is a relationship between responder rate and treatment.
The estimates of the responder rate in each treatment group will be presented along with the 
difference in responder rates. Corresponding confidence intervals for responder rates as well as
difference in responder rates and p-value for difference in responder rates will also be presented. 
In order to investigate the poolability of the results of the primary analysis across different subgroups,
subgroups defined by study center, age (≥55 vs <55), and FST (I-III vs IV-VI) will be used. Logistic
regression models will be fitted which will include the subgroup factor as well as the corresponding 
interaction term (subgroup x treatment) in order to obtain estimates and confidence intervals at each 
level of the subgroup factor. These will be displayed in graphs.
 
  
 
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missing data on the primary endpoint will be evaluated by performing sensitivity analysis based on 
the observed cases in the ITT set.
All other effectiveness endpoints will be evaluated based on the observed cases in ITT.
Descriptive statistics of all safety data will be performed on observed cases.
10.7
Data monitoring committee
Not applicable to this study.
10.8
Withdrawals and deviations
All withdrawn subjects will be listed individually, including at least subject number, date and reason 
for withdrawal, and last visit performed.
Subjects with CIP deviations will be listed individually, including subject number and observed 
deviation. Depending on the seriousness of the deviation, subject might be excluded from the PP 
population, which shall be documented prior to database lock.
Deviations from the statistical plan will be documented in the CSR. If the need of changing the 
statistical plan arises before DBL but after the finalization of the SAP, the SAP will be amended.
10.9
Sample size
A total sample size of approximately 150 subjects will be included in this study; approximately 100 
will be randomized to treatment with Sculptra Aesthetic and approximately 50 will be randomized to 
no treatment. Sample size justifications are given below.
10.9.1 Previous data
Since the primary endpoint will be based on a new scale, no existing data is available. 
10.9.2 Assumptions
Based on what is seen in clinical studies of injectable fillers in the facial areas, it is reasonable to 
assume a responder rate of at least 70% in the Sculptra Aesthetic treatment group at month 12. For the 
no treatment control group, responder rates up to almost 30% have been observed in data on file. 
Based on this, it is assumed that the response rate will be maximum 35% in the no-treatment control 
group at month 12.
10.9.3 Sample size calculations
For the responder rate in 
, testing the difference using a two-sided test at the 5% significance 
level will have approximately 90% power to demonstrate difference between a responder rate of 70% 
in the Sculptra Aesthetic group, and a responder rate of 35% in the no treatment control group when 
the sample sizes are 84 and 42, respectively. Accounting for 15% drop-outs, approximately 150 
subjects need to be randomized in a 2:1 ratio.
11
Protection of personal data
All processing of personal data must be carried out in accordance with national legislation concerning 
the protection of personal data. The Institution and the Investigator are responsible for complying with 
all requirements pursuant to national legislation in which the Institution and the Investigator are 
located. The Sponsor will ensure that all requirements for data processing are fulfilled.
The Investigator understands that clinical  studies  conducted  under an  IDE  are exempt from the  
study subject identifier confidentiality provisions of the Health Insurance Portability and 
Accountability Act of 1996 (HIPAA), and the study subject should be made aware of this exception in 
 
  
 
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the informed consent. The Institution and Investigator are jointly responsible for providing sufficient 
information to all subjects to enable them to give their informed consent not only to the participation 
in the investigation, but also to the processing of Personal Data. Such information includes 
information regarding the purposes of the processing, the length of time during which Personal Data 
will be stored, the right of access to stored Personal Data and the right to correction or purging of 
incorrect or obsolete Personal Data. A subject may also withdraw his or her consent at any time.
A subject who withdraws  his  or  her  consent  to  the  processing  of  Personal  Data must be 
considered to have withdrawn from the investigation but the data collected until the consent was 
withdrawn may be used in the statistical analyses.
Authorized representatives from the Sponsor or a RA may visit the investigational site to perform 
audits/inspections, including source data verification, i.e., comparing data in the subjects’ medical 
records and the eCRF. Data and information will be handled with strict confidentiality.
The study shall include collection and processing of personal data as specified in the Regulation (EU) 
2016/679 (General Data Protection Regulation, GDPR) on the protection of individuals with regard to 
the processing of personal data. For the purposes of the study, Sponsor will be considered the data 
controller, and Institution and PI will both be considered data processors.
12
Quality Control and Quality Assurance
12.1
Quality control
On-site monitoring of the study will be arranged by the Sponsor according to GCP guidelines to 
verify that the rights and well-being of the subjects are protected, the reported data are accurate, 
complete, verifiable from source documents, and that the conduct of the study complies with the 
approved CIP, subsequent amendment(s), GCP and the applicable regulatory requirements. 
Any CIP deviation shall be documented appropriately, verified, discussed, and collected by the 
monitor and appropriate actions will be taken. The PI is responsible for promptly reporting any 
deviations from the CIP that affects the rights, safety or well-being of the subject or the scientific
integrity of the study, including those that occur under emergency circumstances, to the Sponsor as 
well as the IRB if required by national regulations. Deviations will be reviewed to determine the need 
to amend the CIP or to terminate the study.
12.2
Quality assurance
The study site may be subject to quality assurance audit by the Sponsor as well as inspection by 
appropriate RA. It is important that the PI and other relevant study site personnel are available during 
the monitoring visits, possible audits, and inspections, and that sufficient time is devoted to the 
monitoring process.
Each participating member of the study site team shall provide a curriculum vitae (CV) or equivalent
that demonstrates their qualifications to conduct the study.
It is the responsibility of the PI to ensure that all personnel involved in the study are fully informed of 
all relevant aspects of the study, including detailed knowledge of and training in all procedures to be 
followed. All Investigators and other responsible persons shall be listed together with their function in 
the study on the signature and delegation log.
12.3
Changes to the clinical investigational plan
The PI and other site personnel involved in the study must not implement any changes to the CIP
without agreement with the Sponsor and prior review and documented approval from the IRB and 
RA, if applicable, except where necessary to eliminate an immediate hazard to the subjects. All 
changes to the final CIP must be documented in a dated and version-controlled written protocol 
amendment. However, administrative changes may be documented in the Sponsor file without 
 
  
 
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requiring a protocol amendment. The Sponsor will assess if the changes require prior FDA 
approval, and inform the Investigator when such approval has been received.
13
Financing, Indemnification, and Insurance
The CTA outlines the compensation and payment terms of the study. The CTA must be signed before 
the first subject is screened in the study. If there are differences between the CTA and the CIP
regarding certain rights and obligations, the CTA is the prevailing document. Q-Med AB’s obligations 
in this clinical study are covered by Galderma’s global general liability program. An insurance 
certificate will be provided upon request. The Institution/PI is obligated to maintain insurance 
coverage for their obligations in the clinical study according to the CTA.
14
Publication Policy
The PI’s, Institution’s, and Q-Med AB’s obligations regarding intellectual property rights,
confidentiality, and publications are described in detail in the CTA.
The aim is to submit the results of this study for publication in the public database ClinicalTrials.gov 
and to a medical journal for a first joint publication of the results. Everyone who is to be listed as an 
author of the results of this multicenter study shall have made a substantial, direct, intellectual 
contribution to the work. Authorship will be based on (1) substantial contributions to the conception 
or design of the work; or the acquisition, analysis, or interpretation of data for the work; and (2) 
drafting the work or revising it critically for important intellectual content; and (3) final approval of 
the version to be published; and (4) agreement to be accountable for all aspects of the work in 
ensuring that questions related to the accuracy or integrity of any part of the work are appropriately 
investigated and resolved5. Conditions 1, 2, 3, and 4 must all be met in order to be designated as 
author. Those who do not meet all four criteria will be acknowledged. Among the authors that fulfil
the above mentioned criteria, one author will be appointed by Q-Med AB to take primary 
responsibility for the overall work as primary author.
15
Suspension or Premature Termination
The Sponsor will suspend or terminate the study when so instructed by the IRB or RA, or if it is 
judged that the subjects are subjected to unreasonable risks, or for valid scientific or administrative 
reasons, or for business reasons.
The Sponsor may also decide to close a single study site due to unsatisfactory subject enrolment or 
non-compliance with the CIP, GCP, or applicable regulatory requirements.
In the event of premature termination, Q-Med AB will provide information on the handling of 
currently enrolled subjects who have not completed the study.
                                                
5 Defining the role of authors and contributors, compiled by the International Committee of Medical Journal 
Editors (ICMJE) (http://www.icmje.org).
 
  
 
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16
References
1.
WMA Declaration of Helsinki
https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-
medical-research-involving-human-subjects/
2.
Sculptra Aesthetic Instructions for Use 
http://www.galdermausa.com/IFU/Sculptra Aesthetic IFU.pdf
3.
Vleggaar; Fitzgerald, Lorenc et al.Consensus recommendations on the use of injectable Poly-
L-Lactic-Acid for facial and non-facial volumization. Journal of Drugs in Dermatology 2014; 
13 (4): 44-51
4.
GLI.04.SPR.US10321 Sculptra PAS 2-yr Clinical Study Report; data on file MA-39427.
5.
Alessio R, Rzany B, Eve L, Grangier Y, Herranz P, Olivier-Masveyraud F, Vleggaar D. 
European expert recommendations on the use of injectable poly-L-lactic acid for facial 
rejuvenation. J Drugs Dermatol. 2014 Sep;13(9):1057-66.
6.
Schierle, Nonsurgical Rejuvenation of the Aging Face With Injectable Poly-L-Lactic Acid for 
Restoration of Soft Tissue Volume. Aesthetic Surgery Journal 2011 31(1) 95– 109  
7.
Rossner, Rossner, Hartmann, Erdmann, Wiest, Rzany. Decrease of reported adverse events to 
injectable polylactic acid after recommending an increased dilution.J of Cosmetic 
Dermatology 2009:8 (1) 14-18
8.
Alam M, Gladstone H, Kramer EM, et al.  ASDA guidelines of care: injectable fillers.  
Dermatol Surg.  2008; 34 (suppl 1): S115-S148.
9.
The Fitzpatrick Classification Scale for Skin Types
https://www.verywell.com/fitzpatrick-classification-scale-1069226
10. Fitzpatrick T.B. (1988). The validity and practicality of sun-reactive skin types I thru VI. 
Arch. Dermatol. 124, 869-871.
11. Scale Validation Cheek Wrinkles Statistical Report, MA-41231
 
  
 
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Appendix 1
Investigator Signature Page
Signed Agreement of the Clinical Investigational Plan
CTN:
43USSA1812
Title of the CIP:
A randomized, evaluator-blinded, no-treatment controlled, multicenter study 
to evaluate the effectiveness and safety of Sculptra Aesthetic for correction of 
cheek wrinkles
We, the undersigned, have read and understand the Clinical Investigational Plan (CIP) 
specified above, and agree on the contents. The CIP, the clinical trial agreement (CTA)
and the additional information given in the instructions for use (IFUs) and the Report 
of Prior Investigations (ROPI) will serve as a basis for co-operation in this study.
Principal Investigator
Printed name
Signature
Date
Study site
 
  
 
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Sign page:1 of 1
SIGNATURES PAGE
Date
Signed by
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Justification
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Justification
2021-03-24 10:33
Justification
2021-03-24 11:04
Justification
 
  
 
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PPD
PPD
PPD
PPD