Open Label Extension for 43USSA1812 (A Randomized, Evaluator-blinded, No-treatment Controlled, Multi-center Study to Evaluate the Effectiveness and Safety of Sculptra Aesthetic for Correction of Cheek Wrinkles)
Phase: NA
Conditions: Cheek, Wrinkle
Sponsor: Galderma R&D

A copy of the following document is included: 
 
Protocol version 1.0 
effective 29 July 2020 
 
 
 
 
 
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Open label Extension study
for 43USSA1812 (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 product:
Sculptra® Aesthetic
Clinical trial number (CTN):
43USSA1812ext
Sponsor:
Q-Med AB, part of the 
Galderma Group
Seminariegatan 21
SE-752 28 Uppsala,
Sweden
Telephone:
+46 18 474 90 00
Facsimile:
+46 18 474 9001
Confidentiality Statement
This clinical investigational plan (CIP) contains confidential information belonging to Q-Med AB, part 
of the Galderma Group. Except as may be otherwise agreed to in writing, by acceptingor 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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Study Administrative Structure
Global Head of Clinical
Development:
Sponsor’s Medical Expert:
Sponsor’s Scientific Writer:
Sponsor’s Clinical Project Manager:
Sponsor’s Statistician:
Further details on all participating Investigators and the complete administrative structureof the study are 
found in the study files. Note that administrative changes are to bedocumented in the study files without 
requiring a CIPamendment.
 
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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.
Global Head of Clinical Development, Q-Med AB
Senior Medical Expert, Q-Med AB
Statistician, Q-Med AB
 
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assessed live by the subject and the Treating Investigator separately at all 
visits following Month 12 in pivotal study 43USSA1812.

Percentage of subjects responding in each response category for each 
question in the subject satisfaction questionnaire at all visits following 
Month 12 in pivotal study 43USSA1812.

Change from pre-treatment 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 Month 12 in pivotal study 
43USSA1812.
Note:
Pre-treatment = Month 12 (pre-treatment) for Group A subjects (those originally
randomized to the Control Group in pivotal study 43USSA1812). 
Pre-treatment = Day 1 for Group B subjects (those originally randomized to         
the Treatment Group in pivotal study 43USSA1812).

Time to return to social engagement after treatment using subject diaries for 
28 days after each treatment.
Safety Objective
and Endpoint
To evaluate the safety of Sculptra Aesthetic in the treatment of cheek wrinkles.
Safety endpoints include:

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 following each 
treatment.

Safety assessment by a qualified staff member at all visits according to 
predefined methods:
o
Cheek firmness, symmetry and function 
o
Device palpability (pre-treatment assessment excluded for subjects 
receiving treatment in extension study)
o
Mass formation
o
Cheek sensation
o
Visual function assessments (Group A subjects only) 
Subject 
Participation
Subjects who participated in the pivotal study may be involved in the extension 
of the study for approximately 48 weeks from the 43USSA1812 Month 12 Visit)
to the final follow-up visit.
Enrollment
Written informed consent will be obtained before any study related procedure is 
performed. 
 
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Inclusion criteria
The subjects must meet the following criteria to be eligible for the extension 
of the study:
1.
Subject completed Month 12 of study 43USSA1812
2.
Subjects willing to comply with the requirements of the 
extension of the study and providing a signed written informed 
consent.
For subjects eligible for treatment in the extension study:
3.
Female subjects who are exempt from birth control requirements 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 extension study entry visit and prior to all injection 
visits. Acceptable forms of effective birth control methods include:
•
Combined oral contraceptives (estrogens and progesterone) or 
implanted or injectable contraceptives with a stable dose for at 
least 28 days prior to enrollment
•
Hormonal or copper intrauterine device (IUD) inserted at least 
28 days prior to Enrollment
•
Barrier methods of contraception: condom or occlusive cap 
(diaphragm or cervical caps) with spermicidal 
foam/gel/film/cream/suppository
•
Bilateral tubal ligation prior to Enrollment
•
Vasectomized partner (in monogamous relationships) for at least 
3 months prior to Enrollment
•
Strict abstinence (at least one month prior to enrollment and 
agrees to continue for the duration of the study or use acceptable 
form of birth control).
Exclusion criteria
For subjects eligible for treatment in the extension study, the exclusion criteria 
for study 43USSA1812 applies. The presence of any of the exclusion criteria
noted in Section 5.3 will exclude a subject from treatment in the extension study.
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
Not applicable
Treatment
Each subject eligible for treatment in the extension study will receive a single 
regimen of Sculptra Aesthetic. A single regimen consists of up to four (4) 
injection sessions with 1-month (+2 week) intervals. Sculptra Aesthetic will be 
administered using a 25G (gauge) needle using the bolus, fanning, cross-
 
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hatching, linear threading injection technique or other techniques at the 
discretion of the Treating Investigator.  Injections will be made sub-dermally, 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
Study Procedures
Effectiveness Assessments:

Cheek wrinkles by Blinded Evaluator and Treating Investigator using GCWS 

Global aesthetic improvement by Treating Investigator and Subject using 
GAIS.

Subject’s satisfaction after treatment using a Subject Satisfaction 
Questionnaire.

Subject’s satisfaction using FACE-Q “Satisfaction with Cheeks”.

.

Return to social engagement after treatment using subject diaries.

 by Treating 
Investigator.
Evaluation of Safety:

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 following each
treatment.

Safety assessment by a qualified staff member at all visits according to
pre- defined methods:
o
Cheek firmness, symmetry and function (smiling and chewing)
o
Device palpability (pre-treatment assessment excluded for subjects 
receiving treatment in extension study)
o
Mass formation
o
Cheek sensation
o
Visual function assessments (Group A subjects only).
Study Report
A study report will be compiled at the conclusion of the study.
 
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Statistical 
Methods
All effectiveness analyses will be conducted descriptively. Responder rates in 
and GAIS (Investigator’s and subject’s assessments 
separately), will be presented using n, percentage and 95% confidence intervals. 
Results for the right and left side of the face separately as well as combined will 
be presented. FACE-Q and subject satisfaction will be presented descriptively. 
All safety endpoints will be analyzed descriptively. All AEs will be coded 
according to MedDRA. AEs related to study product or injection procedure will 
be summarized by system organ class (SOC) and preferred term (PT) as well as 
by SOC, PT and maximal severity. Time to onset and duration of related AEs 
will also be summarized. Serious AEs will be listed.
Sample Size:  This is an extension of study 43USSA1812. Subjects completing 
the 12-month visit in study 43USSA1812 will be considered for inclusion in the 
extension study.
 
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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
GAIS
GCP
Global aesthetic improvement scale
Good clinical practice 
GCWS
Galderma Cheek wrinkles Scale
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.
IRB
Institutional review board
ISO
International Organization for Standardization
LSFV
Last Subject First Visit
 
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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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4.7.4
Visit 2a, Treatment Follow up 72 hour telephone call (±24 hours) – for subjects who received a 
second treatment only................................................................................................................................26
4.7.5
Visit 3, Treatment 3 (1 month [+2 weeks] after Treatment 2) .....................................................26
4.7.6
Visit 3a, Treatment Follow up 72 hour telephone call (±24 hours) – for subjects who received a 
third treatment only...................................................................................................................................27
4.7.7
Visit 4, Treatment 4 (1 month [+2 weeks] after Treatment 2) .....................................................27
4.7.8
Visit 4a, Treatment Follow up 72 hour telephone call (±24 hours) – for subjects who received a 
fourth treatment only.................................................................................................................................28
4.7.9
Visits 5, 6, and 7: Follow-up, Month 19 (±2weeks), 21 (±2 weeks), and 24 (±2 weeks) ............28
4.7.10    Visits 2, 3 and 4; Follow-up, Months 19 (±2 weeks), 21 (±2 weeks), and 24 (±2 weeks)..........29
4.7.11    Unscheduled Visits......................................................................................................................29
5
Subjects ................................................................................................................................................29
5.1
Subject information and informed consent..................................................................................29
5.2
Inclusion criteria.............................................................................................................................30
5.3
Exclusion criteria............................................................................................................................31
5.4
Subject number...............................................................................................................................33
5.5
Withdrawal of subjects...................................................................................................................33
6
Study Products.........................................................................................................................................33
6.1
Investigational product ..................................................................................................................34
6.2
Reference product...........................................................................................................................35
6.3
Additional products and materials................................................................................................35
6.4
Packaging, labeling, and storage ...................................................................................................36
6.4.1
Investigational product.................................................................................................................36
6.4.2
Reference product.........................................................................................................................36
6.4.3
Product accountability..................................................................................................................36
6.5
Treatment........................................................................................................................................37
6.5.1
Treatment procedure.....................................................................................................................37
6.5.2
Treatment regimen (dose and interval).........................................................................................38
6.5.3
Post-treatment care.......................................................................................................................38
6.5.4
Post-trial provisions......................................................................................................................38
6.5.5
Treatment compliance..................................................................................................................38
7
Effectiveness Assessments.......................................................................................................................38
7.1
Galderma Cheek Wrinkles Scale (GCWS) 
39
7.2
Galderma Cheek Wrinkles Scale (GCWS) 
40
7.3
Global Aesthetic Improvement Scale (GAIS)...............................................................................40
7.4
Subject Satisfaction Questionnaire ...............................................................................................41
7.5
FACE-Q “Satisfaction with Cheeks”............................................................................................42
7.6
......................................................................................42
7.7
Return to social engagement..........................................................................................................42
7.8
..........................................................43
7.9
Photography....................................................................................................................................43
8
Safety Assessments ..................................................................................................................................43
8.1
Assessment of AEs by direct questioning to subject and evaluation of subject.........................44
 
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8.2
Subject Diary Data .........................................................................................................................44
8.3
Laboratory assessments .................................................................................................................44
8.4
Visual Function assessments..........................................................................................................44
8.4.1
Snellen visual acuity test..............................................................................................................45
8.4.2
Extraocular muscle function test ..................................................................................................45
8.4.3
Confrontation visual field.............................................................................................................45
8.5
Other safety assessments – All Subjects .......................................................................................45
8.5.1
Cheek sensation............................................................................................................................45
8.5.2
Cheek firmness, symmetry and function......................................................................................46
8.5.3
Mass formation.............................................................................................................................46
8.5.4
Device palpability- All Subjects...................................................................................................46
8.6
Adverse events.................................................................................................................................46
8.6.1
Definition of an adverse event......................................................................................................46
8.6.2
Definition of a serious adverse event ...........................................................................................46
8.6.3
Definition of unanticipated adverse effect ...................................................................................47
8.6.4
Recording instructions..................................................................................................................47
8.6.5
Reporting of adverse events .........................................................................................................48
8.6.6
Reporting of adverse events of special interest (AESIs)..............................................................48
8.6.7
Reporting of serious adverse events.............................................................................................49
8.6.8
Stopping Rule...............................................................................................................................50
8.6.9
Reporting of unanticipated adverse device effects.......................................................................50
8.6.10
Follow-up of unresolved events ongoing at termination of the study......................................50
8.6.11
Reporting and follow-up of events occurring after subject termination of the study...............50
8.6.12
Pregnancy.................................................................................................................................50
8.6.13
Anticipated adverse events.......................................................................................................51
8.7
Device deficiencies ..........................................................................................................................51
8.7.1
Definition of a device deficiency .................................................................................................51
8.7.2
Recording instructions..................................................................................................................51
8.7.3
Reporting of device deficiencies ..................................................................................................51
9
Data Handling and Management...........................................................................................................52
9.1
Data management...........................................................................................................................52
9.2
Electronic case report forms..........................................................................................................52
9.2.1
Data entry .....................................................................................................................................53
9.2.2
The query process.........................................................................................................................53
9.2.3
User identification........................................................................................................................53
9.2.4
Audit trail .....................................................................................................................................53
9.3
Source documents...........................................................................................................................53
9.4
Record keeping and access to source data....................................................................................54
9.5
Document and data retention ........................................................................................................54
10
Statistical Methods ..................................................................................................................................54
10.1
General ............................................................................................................................................54
10.2
Analysis populations.......................................................................................................................54
10.3
Demographics, baseline assessments, and subject characteristics .............................................55
10.4
Effectiveness analysis......................................................................................................................55
10.5
Safety analysis.................................................................................................................................55
10.6
Handling of missing data................................................................................................................56
 
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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 medicaldevice.
1.2
Application to Institutional Review Board and/or Regulatory Authorities
It is the responsibility of the Principal Investigator (PI) to obtain approval of the CIP/CIP amendment
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 DrugAdministration (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 collection, access to, processing, and transfer of protected health information or sensitive personal 
data shall be carried out in accordance with applicable regional or national 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 contour deficiencies and other facial wrinkles.
Study 43USSA1812ext is an extension to pivotal study 43USSA1812 to assess the long-term 
effectiveness and safety of Sculptra Aesthetic for the treatment of cheek wrinkles. Safety and 
effectiveness data for both study groups (A and B) will be collected for up to 12 months. In all, subjects 
will be followed for 24 months after baseline in pivotal study 43USSA1812.
2.2
Study product Profile
2.2.1
Investigational product description
Sculptra Aesthetic is a poly-L-lactic acid implant in the form of a suspension, which is reconstituted from 
a sterile dry powder by the addition of sterile water for injection. Poly-L-lactic acid (PLLA) is the main 
active ingredient from which the product has achieved its intended purpose. Sodium 
carboxymethylcellulose (CMC) acts as a suspending agent for maintaining an even distribution of PLLA 
particles following reconstitution. Mannitol enhances the lyophilization process and provides the 
suspension with a consistency that is suitable for injection.
Each vial of dry powder contains 150 mg PLLA, 90 mg CMC and 127.5 mg non-pyrogenic mannitol – in 
total a vial weight of 367.5 mg and is per approved label to be reconstituted prior to use by the addition 
of 5 mL of SWFI to form a sterile non-pyrogenic suspension. (2) In this study, commercially available 
Sculptra Aesthetic labeled for the study will be used and reconstitution will be made with 8 mL of SWFI 
with addition of 1 mL of 2% lidocaine prior to injection. It h as been recommended by experienced 
physicians to evaluate alternative reconstitution procedures for Sculptra Aesthetic compared to the 
 
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currently approved instructions for use, primarily to enhance safety of the device by potentially reducing 
incidence of nodule and papule formation. (3).
2.2.1.1
Non-clinical documentation
2.2.1.2
Clinical documentation
Please refer to the Sculptra Aesthetic Instructions for Use (IFU) document. The study specific IFU 
summarizes the adverse effects experienced with Sculptra Aesthetic injections alongwith precautions that 
can minimize these potential complications. For intravascular complications and recommended 
treatments, refer to the Intravascular Treatment Protocol.
Please refer to the study Report of Prior Investigations (ROPI) for a description ofperformed non-clinical 
and clinical studies and results with Sculptra Aesthetic.
2.3
Study rationale and justification for design
This study is an extension of study 43USSA1812, which evaluated the effectiveness and safety of Sculptra 
Aesthetic for treatment of cheek wrinkles, with the objective of an expanded label indication. The purpose 
of this extension of the study is to evaluate long-term safety and effectiveness data of Sculptra Aesthetic
beyond the Month 12 duration of the pivotal study 43USSA1812, to help characterize the long-term safety 
and effectiveness profile of the more dilute suspension. 
2.4
Risks and benefits
Anticipated benefits for subjects treated with Sculptra Aesthetic for the correction of cheek wrinkles 
include restoration of a more youthful appearance, relatively long-lasting effects that would reduce the 
need for frequent touch-up procedures. Another benefit is better knowledge about the safety profile for 
Sculptra Aesthetic in the new reconstitution volume, including assessment of the risks for late onset 
papules, nodules, and granuloma as well as other potential adverse event cases associated with Sculptra 
Aesthetic.
The benefit of Sculptra Aesthetic for correction of cheek wrinkles is also being evaluated in the ongoing, 
post-approval US clinical study (US10321). (4) Although treatment in the cheek area was secondary to 
treatment in the nasolabial folds in this study, the interim data results support that treatment for cheek 
wrinkles is effective and well tolerated.
Since the initial approval of Sculptra Aesthetic in 1999 (EU), the amount of SWFI used to reconstitute 
Sculptra Aesthetic has gradually increased. Based on medical literature and physician experience, 
practitioners have reported improved clinical outcomes with increased reconstitution volumes that are up 
to two times higher than the volume recommended by the manufacturer and usually in combination with 
anesthetic solutions, like lidocaine 2%. (3, 5) It has also been suggested, that a reduction in frequency of 
nodules/papules can be achieved with an increased reconstitution volume. (6, 7). 
Most recently, the increased reconstitution volume for treatment of nasolabial folds was evaluated in study 
43USSA1705. 
Risks with Sculptra Aesthetic as with any other injectable implant include infections, perforation of blood 
vessels, trauma to nerves and lumps. The most common reported adverse events (AEs) after Sculptra 
Aesthetic treatments are formation of papules and nodules, swelling, mass/induration, of which most 
resolve with time.
Infection, and damage to body structures such as nerves or blood vessels at the injection site, have also 
been reported. Rare but serious AEs associated with the intravascular injection of soft tissue fillers in the 
face have been reported and include temporary or permanent vision impairment, blindness, cerebral 
 
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ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial
structures.
Assessments for visual disturbance have been implemented at baseline, all treatment and all follow-up 
visits with specific instructions to immediately see an ophthalmologist or retina expert should any visual 
disturbance event occur. Moreover, only study Investigators qualified by education and experience, and 
who are skilled in the use of soft tissue fillers from their clinical practice and involvement in clinical 
research, and with a firm knowledge of the vascular anatomy and understanding of the depth and plane 
of injection as well as knowledge of the signs and symptoms and management of potential 
complications, will be chosen in order to assure proper device implantation and management of study 
risk. 
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.
Lidocaine can, in rare cases, give allergic reactions, and therefore subjects with known allergy or 
hypersensitivity to local anesthetics should not be included in the study.
Additional information about reported AEs and anticipated risks are included in the study Instructions 
for use (IFU) and ROPI. Stopping rules for the study are included in Section 8.6.8. Given the anticipated 
low level of acceptable AEs in connection with the injection and the protocol required safety assessments,
it was determined the risk-benefit assessment for use of Sculptra Aesthetic using investigational 
reconstitution and injection procedures for correction of cheek wrinkles appears to offer a clinical benefit 
at reasonable risk.
3
Objectives and Endpoints
3.1
Effectiveness objective and endpoints
The objective is to evaluate the long-term effectiveness of Sculptra Aesthetic in the correction of cheek 
wrinkles.
Effectiveness endpoints include:

Responder rate, using the 
 (GCWS) 
 as assessed live by the 
Blinded Evaluator at Months 19, 21 and 24.
A responder is defined as a subject with at least 1 grade improvement from pre-treatment on both 
cheeks concurrently.

Responder rate, using the 
 (GCWS) 
c, as assessed live by the 
Blinded Evaluator, at Months 19, 21 and 24.

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 Month 12 in pivotal study 43USSA1812.

Percentage of subjects responding in each response category for each question in the subject 
satisfaction questionnaire at all visits following Month 12 in pivotal study 43USSA1812.

Change from pre-treatment 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 Month 12 in pivotal study 
43USSA1812.
Note: Pre-treatment = Month 12 (pre-treatment) for Group A subjects (those originally randomized to 
the Control Group in pivotal study 43USSA1812). Pre-treatment = Day 1 for Group B subjects (those 
originally randomized to the Treatment Group in pivotal study 43USSA1812).
 
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
Time to return to social engagement after treatment using subject diaries for 28 days after each 
treatment.  
3.2
Safety objective and endpoints
To evaluate the safety of Sculptra Aesthetic in the treatment of cheek wrinkles.
Safety endpoints include:

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 following each treatment.

Safety assessment by a qualified staff member at all visits according to predefined methods:
o
Cheek firmness, symmetry and function 
o
Device palpability (pre-treatment assessment excluded for those receiving treatment in the 
extension study)
o
Mass formation
o
Cheek sensation
o
Visual function assessments (Group A subjects only)
4
Design of the Study
4.1
General outline
This is a 12-month extension of the prospective, randomized, evaluator- blinded, no-treatment 
controlled study 43USSA1812.
Subjects originally randomized to Control Group (approximately 50 subjects) in the pivotal study will be 
offered treatment with Sculptra Aesthetic in the extension study.  This group of subjects is designated as 
Group A within this protocol.  
Subjects originally randomized to Treatment Group (approximately 100 subjects) in the pivotal study
will be continued to be followed up during the extension study without further treatment. This group of 
subjects is designated as Group B within this protocol.  
Safety and effectiveness data will be collected for up to 24 months in subjects randomized to the 
Treatment Group (who are not treated in the extension study) and for up to 12 months in subjects 
randomized to the Control Group (who are treated in the extension study). In all, subjects will be followed 
for 24 months after the baseline visit in the pivotal study.
Note: One month is defined as 4 weeks in the study.
 
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Concomitant therapies are defined as follows:

Any therapy ongoing at the time the subject exited study 43USSA1812, Month 12.

Any changes to existing therapies (such as changes in dose or formulation) duringthe course 
of the study, or

Any new therapies started after exiting study 43USSA1812 Month 12.
4.6.2
Categories
The following three categories are to be considered for 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
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:

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.:
 
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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
43USSA1812ext Visit 1: Entry visit (all subjects)

The 43USSA1812 Month 12 visit is the final visit in the pivotal study and may also serve as 
the Entry visit for extension study 43USSA1812ext.  The entry visit can also be performed as 
a separate visit within 2 weeks of 43USSA1812 Month 12 visit. When both visits occur at the 
same day, assessments need only to be performed once. 
The following activities will be performed: 

Informed consent (prior to conducting any extension study specific procedure)

Assess eligibility for extension study (inclusion and exclusion criteria)
Visit 1:  Group A Subjects (those receiving Treatment in 43USSA1812ext):
  Once the subject is deemed otherwise eligible by the Treating Investigator, the following procedures 
should be completed:

Review concomitant therapies

Obtain weight

Assess and interview for AEs – Investigator

Perform safety assessments: Cheek sensation, Cheek firmness, symmetry and function, Mass 
formation.

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.

Perform Visual function assessments: Snellen visual acuity test, Extraocular muscle function 
test and Confrontation visual field 

Obtain Photography 2D and 3D (perform prior to treatment)

Instruct the subject to complete FACE-Q assessment

 – Treating Investigator.

Assess GAIS - Investigator and subject.

Assess GCWS 
– Treating Investigator and Blinded Evaluator (pre-
treatment)

Sculptra Aesthetic administration 

Evaluate for device deficiencies

Dispense diary and instruct subject on daily Diary completion. Remind subject to bring the 
Diary to the next on-site visit.

30 minutes following injection, perform Visual Function Assessments.

Evaluate the subject for post-treatment AEs- Treating Investigator    

Schedule the next follow up visit (1 month [+2 weeks])
Visit 1:  Group B Subjects (those originally randomized to Treatment Group in pivotal 43USSA1812
study):
Once the subject is deemed otherwise eligible by the Treating Investigator, the following procedures 
should be completed:

Review concomitant therapies
 
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
Obtain weight

Assess and interview for AEs – Investigator

Perform safety assessments: Cheek sensation, Cheek firmness, symmetry and function, Mass 
formation and Device Palpability
(Visual Function assessments performed as part of 43USSA1812 pivotal final study visit only)

Assess GCWS (
)- Blinded Evaluator

Obtain Photography (2D and 3D)

GAIS: Perform GAIS assessment - Investigator and Subject.

Instruct the subject to complete FACE-Q assessment

t – Treating Investigator.

Instruct the subject to complete the Subject satisfaction questionnaire

Assess and interview for AEs – Investigator
Note:  Visits described below in Sections 4.7.2  through 4.7.9  pertain to Group A subjects only. 
See Section 4.7.10 for Group B subjects follow up visits.
4.7.2
Visit 1a, Treatment Follow up 72 hour telephone call (±24 hours) 
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.
4.7.3
Visit 2, Treatment 2 (1 month [+2 weeks] after Treatment 1)

Review the subject’s concomitant therapies.

Collect and review subject diary.

Interview for AEs.

Assess for AEs – Treating Investigator

Assess GCWS 
 Treating Investigator  (pre-treatment) 

Obtain Photography 2D and 3D (if receiving a treatment at this visit, perform prior to 
treatment)

Perform Visual Function Assessments for all subjects (if receiving a treatment at this visit, 
perform prior to treatment).

Perform safety assessments: Cheek sensation, Cheek firmness, symmetry and function, Mass 
formation and Device Palpability.   

GAIS: Perform GAIS assessment (if receiving a treatment at this visit, perform prior to 
treatment) - Investigator and Subject. 

Instruct the subject to complete the Subject satisfaction questionnaire (pre-treatment). 

Instruct the subject to complete Face-Q assessment.
 
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
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 +2 weeks) after treatment 2 visit 
4.7.4
Visit 2a, Treatment Follow up 72 hour telephone call (±24 hours) – for subjects who 
received a second treatment only.
•
Interview subject regarding any concomitant therapies
•
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.
•
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.
4.7.5
Visit 3, Treatment 3 (1 month [+2 weeks] after Treatment 2) 

Review the subject’s concomitant therapies.

Collect and review subject diary (only applicable for subjects who received a treatment at 
Treatment 2 visit).

Interview for AEs.

Assess for AEs- Treating Investigator

Assess GCWS (at rest and dynamic) Treating Investigator  (if receiving a treatment at this 
visit, perform prior to treatment) 

Obtain Photography 2D and 3D  (if receiving a treatment at this visit, perform prior to 
treatment)

Perform Visual Function Assessments for all subjects (if receiving a treatment at this 
visit, perform prior to treatment).

Perform safety assessments: Cheek sensation, Cheek firmness, symmetry and function, 
Mass formation and Device Palpability. 
 
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
GAIS: Perform GAIS assessment (if receiving a treatment at this visit, perform prior to 
treatment) - Investigator and Subject. 

Instruct the subject to complete the Subject satisfaction questionnaire (pre-treatment). 

Instruct the subject to complete Face-Q assessment.

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 +2 weeks) after treatment 3 visit 
4.7.6
Visit 3a, Treatment Follow up 72 hour telephone call (±24 hours) – for subjects who 
received a third treatment only.
•
Interview subject regarding any concomitant therapies
•
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.
•
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.
4.7.7
Visit 4, Treatment 4 (1 month [+2 weeks] after Treatment 2) 

Review the subject’s concomitant therapies.

Collect and review subject diary (only applicable for subjects who received a treatment at 
Treatment 3 visit).

Interview for AEs.

Assess for AEs- Treating Investigator

Assess GCWS (at rest and dynamic) Treating Investigator  (if receiving a treatment at this 
visit, perform prior to treatment) 

Obtain Photography 2D and 3D  (if receiving a treatment at this visit, perform prior to 
treatment)
 
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
Perform Visual Function Assessments for all subjects (if receiving a treatment at this 
visit, perform prior to treatment).

Perform safety assessments: Cheek sensation, Cheek firmness, symmetry and function, 
Mass formation and Device Palpability. 

GAIS: Perform GAIS assessment (if receiving a treatment at this visit, perform prior to 
treatment) - Investigator and Subject. 

Instruct the subject to complete the Subject satisfaction questionnaire (pre-treatment). 

Instruct the subject to complete Face-Q assessment.

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 Visit 1 
4.7.8
Visit 4a, Treatment Follow up 72 hour telephone call (±24 hours) – for subjects who 
received a fourth treatment only.
•
Interview subject regarding any concomitant therapies
•
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.
•
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.
4.7.9
Visits 5, 6, and 7: Follow-up, Month 19 (+2weeks), 21 (±2 weeks), and 24 (±2 weeks) 

Obtain weight measured at clinic.

Review the subject’s concomitant therapies.

Collect and review subject diary (only applicable for subjects in the treatment group who 
received a treatment at Treatment 4 visit).

Obtain 2D and 3D Photographs.
 
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It is the responsibility of the Investigator 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 effect onhis/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 andthe Investigator 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 anyother 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 extension of the study:
1.
Subject completed Month 12 of study 43USSA1812
2.
Subjects willing to comply with the requirements of the extension of the study and 
providing a signed written informed consent.
For subjects eligible for treatment in the extension study:
3.
Female subjects who are exempt from birth control requirements 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 extension study entry visit and prior to all injection visits. 
Acceptable forms of effective birth control methods include:
•
Combined oral contraceptives (estrogens and progesterone) or implanted or injectable 
contraceptives with a stable dose for at least 28 days prior to enrollment
•
Hormonal or copper intrauterine device (IUD) inserted at least 28 days prior to 
Enrollment
•
Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical 
caps) with spermicidal foam/gel/film/cream/suppository
•
Bilateral tubal ligation prior to Enrollment
•
Vasectomized partner (in monogamous relationships) for at least 3 months prior to 
Enrollment
•
Strict abstinence (at least one month prior to enrollment and agrees to continue for 
the duration of the study or use acceptable form of birth control).
 
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5.3
Exclusion criteria
For Group A subjects eligible for treatment in the extension study, the exclusion criteria for study 
43USSA1812 applies. The presence of any of the following exclusion criteria will exclude a subject 
from treatment in the extension 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 fillers (other than Sculptra Aesthetic treatments as part of 
43USSA1812) prior to enrollment in the extension study:
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.
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 
 
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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 enrollment into the extension study or systemic retinoid treatment within 6 months of
enrollment into the extension study.
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 pretreatment 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.
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 throughout the duration of the study.
 
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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 keep the same subject number as in study 
43USSA1812. The subject number, subject name, and other information sufficient to link the eCRF to 
the medical records (e.g. national identification number, chart number, etc.) shall be recorded.
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 
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.
 
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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 
immediately prior to injection
Recommended Maximum 
Volume per treatment 
session

Maximum of 18 mL (2 vials) of Sculptra Aesthetic will 
be administered per treatment session

Maximum of 9 mL (1 vial) per cheek, evenly distributed 
within the treatment area.
Frequency intervals
Four (4) injection sessions with 1-month (+2weeks).
Reconstitution needle size
18G
Injection needle size
25G
 
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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)

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.
 
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6.4
Packaging, labeling, 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
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 shall be 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
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.
 
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6.5
Treatment
6.5.1
Treatment procedure
The investigational product is reserved for use by Treating Investigators who are experienced 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:
o
Superior border - from top of tragus to top of alar crease
o
Medial border - from top of the alar crease, along the NLF to the inferior border of 
the mandibular ramus
o
Inferior border - from medial border at mandibular ramus to angle of mandibular 
ramus
Lateral border - from angle of mandibular ramus to top of tragus 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 
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7.4
Subject Satisfaction Questionnaire
Subject satisfaction with treatment result will be assessed using a subject satisfaction questionnaire.
 
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Subjects will be asked to complete the following questions in the subject diary:
Did you feel comfortable to return to social engagement today?
•
Yes or No
If yes, what was the earliest time you felt comfortable to return to social engagement?
•
Record Date and Time (using 24-hour clock)
7.8
 after treatment 
based on review of baseline photographs and live assessment by responding to the following 
questions:
7.9
Photography
Photographs shall be taken at the time points indicated in the Schedule of Events. For subjects being 
treated, this should occur prior to the first injection of the study product and before each additional 
treatment.  Camera equipment will be provided by the Sponsor or their designee and standardized 
photographs should be taken. Instructions for photography are provided in a separate photography 
manual. Baseline photographs may be used as a reference in the assessment of GAIS by the Treating 
Investigator and subject.  Photographs may also be taken to document AEs at the Treating Investigator’s 
discretion.  Any personnel who were not previously trained in the photographic equipment and 
technique will be trained in the same manner as for study 43USSA1812, prior to extension study start.  
8
Safety Assessments
Safety assessments for this study include an evaluation and an interview of the subjects at each visit to 
obtain information about any medical occurrence that meets the definition of an AE, a subject diary, 
 
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pregnancy tests, cheek firmness, function and symmetry, device palpability (pre-treatment assessment 
excluded for those in Group A), mass formation, cheek sensation and visual function assessments 
(Group A only).
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 enrollment (i.e. Informed 
consent).  Definition and Reporting requirements are found in Section 8.6. 
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.  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 n 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 8.6.5.
8.2
Subject Diary Data
A subject diary will be dispensed to all subjects receiving treatment in the extension study 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 eligible for treatment and of childbearing potential, including those currentlyusing 
contraception, a urine pregnancy test will be performed at each treatment visit prior to injection. The 
test result must be negative for the subject to receive anytreatment with study product.  The test 
result will be documented in source data and the eCRF.
8.4
Visual Function assessments
Visual function assessments will only be performed for subjects receiving treatment in the extension 
study (Group A).  These assessments will be performed both prior to and post injection of the study 
product at all treatment visits and will also be performed at each follow up visits.  The post-treatment 
 
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assessments should be performed 30 min after the injections are completed. In the event of blindness or 
any significant ophthalmic sign or symptom, 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 – All Subjects
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. For subjects in Group A, product palpability assessments will be performed at each 
physical visit after treatment with the study product.  For those in Group B, 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 
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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. 
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 Enrollment 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- All Subjects
Device palpability will be assessed at post treatment visits for Group A subjects and at all physical 
visits for those in Group B, 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
                                                
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 
 
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2. a permanent impairment of a body structure or body function, or
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 enrollment.  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)
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)
                                                
were more severe. (Source: ICH-E2A clinical safety data management: definitions and standards for expedited 
reporting).
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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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
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, 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 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.
8.6.12 Pregnancy
Pregnancy itself is not regarded as 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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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 
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.
 
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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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Appendix 1
Investigator Signature Page
Signed Agreement of the Clinical Investigational Plan
CTN:
43USSA1812ext
Title of the CIP:
Open label extension study for - 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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