A Randomized, Evaluator-blinded, Multi-center Study to Evaluate the Safety and Effectiveness of Sculptra Aesthetic for Correction of Nasolabial Folds.
Phase: NA
Conditions: Nasolabial Folds
Sponsor: Galderma R&D



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Study Administrative Structure
Sponsor:
Q-Med AB, a Nestle Skin Health Affiliate
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 structure of 
the study are found in the study files. Note that administrative changes are to be documented 
in the study files without requiring a Clinical Investigational Plan (CIP)amendment.
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Abbreviations and Definitions of Terms
AE
Adverse event
AESI
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.
CE
French: Conformité Européenne
CFR
Code of Federal Regulations
Childbearing potential
A female (including pre-menopausal subjects) capable of becoming 
pregnant. This includes women on oral, injectable or mechanical 
contraception; women who are single, women whose husbands have 
been vasectomized or whose husbands have received or utilizing 
mechanical contraceptive devices.
CIP
Clinical Investigational Plan
CRF
Case report form
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
ET
Early Termination
FDA
United States Food and Drug Administration
First treatment
Initial injection of study product
FST
Fitzpatrick Skin Type
G
Gauge
GCP
Good Clinical Practice
HA
Hyaluronic acid
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
ICF
Informed Consent Form
ICH
International Conference on Harmonisation
IFU
Instructions for use
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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.
IP
Investigational Product
IPL
Intense Pulsed Light
IRB
Institutional Review Board
ISO
International Organization for Standardization
IUD
Intrauterine Device
MedDRA
Medical dictionary for regulatory activities
Nasolabial Fold (NLF)
Lines between the nose and the corner of the mouth
NSAID
Non-Steroidal Anti-Inflammatory 
Drugs
PLLA
Poly-L-lactic acid
PI
Principal Investigator; qualified person responsible for conducting 
the study at a study site
PP
Per Protocol
PT
Preferred Term
QA
Quality Assurance
RA
Regulatory Authority
ROPI
Report of Prior Investigations, i.e. compilation of the current 
clinical and non-clinical information on the investigational product, 
relevant to the clinical study
Reference product
Sculptra Aesthetic reconstituted with 5 mL of SWFI 
SAE
Serious Adverse Event
SDV
Source Data Verification
SWFI
Sterile Water for Injection
SOC
System Organ Class
SOE
Schedule of Events
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Table of Contents
Study Administrative Structure.............................................................................................................................2
Sponsor Signatures...............................................................................................................................................3
Synopsis ...............................................................................................................................................................4
Abbreviations and Definitions of Terms.............................................................................................................14
List of Tables......................................................................................................................................................20
List of Figures ....................................................................................................................................................20
1.
Ethical Considerations...............................................................................................................................21
1.1
Statement of ethical compliance.................................................................................................................................21
1.2
Application to Institutional Review Board and/or Regulatory Authorities.................................................................21
2.
Background Information ...........................................................................................................................21
2.1
Indication and population description.........................................................................................................................21
2.2
Investigational and Reference product description.....................................................................................................22
2.3
Clinical documentation...............................................................................................................................................23
2.4
Study rationale and justification for design ................................................................................................................23
2.5
Risks and benefits.......................................................................................................................................................24
3.
Objectives and Endpoints..........................................................................................................................25
3.1
Safety objective and endpoints...................................................................................................................................25
3.2
Effectiveness objective and endpoints........................................................................................................................26
4.
Design of the Study....................................................................................................................................26
4.1
General outline ...........................................................................................................................................................26
4.2
Number of subjects.....................................................................................................................................................29
4.3
Duration of subject participation ................................................................................................................................29
4.4
Randomization and blinding.......................................................................................................................................29
4.5
Medical history...........................................................................................................................................................30
4.6
Prior and concomitant therapies .................................................................................................................................30
4.6.1
Definition ...................................................................................................................................................................30
4.6.2
Concomitant therapies are defined as follows: ...........................................................................................................30
4.6.3
Concomitant medication, treatments and procedures .................................................................................................30
4.7
Schedule of events......................................................................................................................................................32
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7.7.9
Pregnancy...................................................................................................................................................................55
7.7.10
Anticipated adverse events .........................................................................................................................................56
7.8
Device deficiencies.....................................................................................................................................................56
7.8.1
Definition of a device deficiency................................................................................................................................56
7.8.2
Recording instructions................................................................................................................................................56
7.8.3
Reporting of device deficiencies.................................................................................................................................56
8. Effectiveness Assessments.............................................................................................................................57
9
Data Handling and Management ...............................................................................................................60
9.1
Data management.......................................................................................................................................................60
9.2
Electronic case report forms.......................................................................................................................................60
9.2.1
Data entry...................................................................................................................................................................61
9.2.2
The query process.......................................................................................................................................................61
9.2.3
User identification ......................................................................................................................................................61
9.2.4
Audit trail ...................................................................................................................................................................61
9.3 Source documents...................................................................................................................................................................61
9.4 Record keeping and access to source data...............................................................................................................................62
9.5 Document and data retention ..................................................................................................................................................62
10
Statistical Methods ....................................................................................................................................62
10.1  General.................................................................................................................................................................................62
10.2 Analysis populations.............................................................................................................................................................63
10.3
Demographics, baseline assessments, and subject characteristics ..............................................................................63
10.4 Primary effectiveness analysis ..............................................................................................................................................63
10.5 Secondary effectiveness analysis ..........................................................................................................................................64
10.6
Safety analysis............................................................................................................................................................64
10.7
Subgroup analyses......................................................................................................................................................65
10.8 
Handling of missing data............................................................................................................................................65
10.9
Interim analysis ..........................................................................................................................................................65
10.10
Withdrawals and deviations........................................................................................................................................65
10.11
Sample size.................................................................................................................................................................65
11
Protection of personal data........................................................................................................................66
12
Quality Control and QualityAssurance.....................................................................................................66
12.1
Quality control............................................................................................................................................................66
12.2
Quality assurance .......................................................................................................................................................67
12.3
Changes to the clinical study protocol........................................................................................................................67
13
Financing, Indemnification, and Insurance ...............................................................................................67
14
Publication Policy......................................................................................................................................67
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7.7
Adverse events
7.7.1
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 persons7, 
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
7.7.2
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-threatening8 illness or injury, or
2. a permanent impairment of a body structure or body function, or
3. in-patient or prolonged hospitalization9, 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
An AE does not need to be recorded as a SAE if it only represents a relapse or an expected
change or progression of the condition that was the cause of the treatment, without the 
development of new symptoms and signs.
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 7.7.6).
7.7.3
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 to the eCRF.  Each subject
should be questioned about AEs at each study visit following randomization and or treatment. 
The question asked should be: “Since your last clinical visit have you had any health 
problems?” Information on AEs can also be obtained from signs and symptoms detected
during each examination.
7 For users or other persons, this definition is restricted to events related to the investigationalproduct.
8 The term “life threatening” in the definition of “serious” refers to an event in which the patient was at riskof death at the
time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe. (Source: 
ICH E2A clinical safety data management: definitions and standardsfor expedited reporting).
9 Planned hospitalization for a pre existing condition, or a procedure required by the CSP, withoutserious deterioration in 
health, is not considered a SAE. (Source:ISO14155:2011).
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Exceptions from AE reporting are normal fluctuations in pre-existing diseases. However, pre-
existing illnesses that deteriorates (in intensity or frequency) shall be reported as AEs.
When an AE is related to a device deficiency (refer to section 7.8), including technical
device malfunction, the AE shall be recorded on the AE form in the eCRF and the technical
complaint shall be reported separately on the clinical study complaint form.
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)
Description of event and 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 7.7.3.1)
f)
Seriousness (serious or not serious, according to definition in Section 7.7.3.2)
g)
Causal relationship to study product or study product injection procedure (yes or no)
h)
Action taken (none, medication treatment, non-medication treatment, or other
procedures/tests, subject withdrawn)
i)
Outcome of the AE (ongoing, recovered, recovered with sequelae, death, chronic/ 
stable, not recovered at the end of the study)
The pre-defined, expected post-treatment events shall be assessed separately. These event 
shall be collected daily by subjects in a Diary for up to 28 days after each treatment.
7.7.3.1 Intensity
Intensity will be recorded for each reported AE. The following definitions of intensity areto 
be used:
Mild:
Awareness of symptoms or signs, but easily tolerated (acceptable)
Moderate:
Enough discomfort to interfere with usual activity (disturbing)
Severe:
Incapacity to work or to do usual activity (unacceptable)
If the intensity changes within one day, the maximum intensity of the AE during that day 
shall be recorded.
7.7.3.2
Causal relationship and seriousness
Each AE, serious as well as non-serious, shall be assessed by the Investigator for causal
relationship with the study product and its use (the injection procedure) and for seriousness 
(Yes or No) of the event.
A two-point scale (Yes or No response) shall be used for the causality assessments. The 
Investigators shall be asked to indicate a response to each of the following questions in the 
eCRF:

“Do you consider that there is a reasonable possibility that the event may have been
caused by the study product?”, and

“Do you consider that there is a reasonable possibility that the event may have been 
caused by the study product injection procedure?”
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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, every efforts should be made to 
complete the eCRFs within a reasonable time frame 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 bythe 
appropriate study personnel (i.e. data manager, site monitor, etc.)
9.2.3
User identification
eCRF records will be automatically appended with the identification of the creator, bymeans 
of their unique User ID. Specified records shall be electronically signed by the Investigatorto 
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 User ID and password; date andtime 
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
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On-site monitoring of the study will be arranged by the Sponsor according to GCPguidelines 
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 reported in the eCRF, which will be verified, discussed, and 
collected by the monitor and appropriate actions will be taken. The Investigator 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 thatoccur 
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. Handling of CIP deviations will be performed as described in the 
monitoring manual.
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 Investigator 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 Investigator to ensure that all personnel involved in the studyare 
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 study protocol
The Investigator and other site personnel involved in the study must not implement any 
deviation from or changes to the CIP without agreement with the Sponsor and prior review 
and documented approval from the IRB except where necessary to eliminate an immediate 
hazard to the subjects. All changes to the final CIP must be documented in a written protocol 
amendment. However, administrative changes are to 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. The Sponsor’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/Investigator is obligated to maintain insurance coverage for their obligations inthe 
clinical study according to the CTA.
14 Publication Policy
The Investigator’s, Institution’s, and Sponsor’s obligations regarding intellectual property 
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rights, confidentiality, and publications are described in detail in the CTA.
This study will be displayed on clinicaltrials.gov in accordance with local regulations. The 
aim is to submit the results of this study for publication. Everyone who is to be listed as an 
author of the publication 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 resolved12. 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 
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 FDA, 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 unsatisfactorysubject 
enrollment or non-compliance with the CIP, GCP, or applicable regulatoryrequirements.
In the event of premature termination, the Sponsor will provide information on the handling 
of currently enrolled subjects who have not completed the study.
12Defining the role of authors and contributors, compiled by the International Committee of Medical Journal
Editors (ICMJE)(http://www.icmje.org).
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17 Appendices
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