Open Label Extension Study for 43USSA1705 (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

Page 1 of 37
Open label Extension study
for 43USSA1705 (A randomized, evaluator-blinded, multi-center study to evaluate the safety and 
effectiveness of Sculptra Aesthetic for correction of nasolabial folds)
Study product:
Sculptra® Aesthetic
Clinical trial number (CTN):
43USSA1705ext 
Sponsor:
Q-Med AB, a 
 
 
 
 
  
 
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Study Administrative Structure
Sponsor:
Q-Med AB, a Galderma 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 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.
  
 
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Synopsis
Title of study
Open label Extension study for 43USSA1705 (A randomized, evaluator-blinded, 
multi-center study to evaluate the safety and effectiveness of Sculptra Aesthetic 
for correction of nasolabial folds)
Clinical Trial 
Number
43USSA1705ext
Countries involved
United States
Number of sites
Approximately 5 sites.  
 
Number of subjects
Approximately 60 subjects
 
 
 
Safety Objective
and Endpoint
The objective is to evaluate the long-term safety of Sculptra Aesthetic as a single 
regimen for correction of Nasolabial Fold (NLF) contour deficiencies
Safety endpoint

Incidence, intensity, time to onset and duration of adverse events collected 
throughout the study period.
Effectiveness 
Objective and 
Endpoints
The objective is to evaluate the long-term effectiveness of Sculptra Aesthetic as a 
single regimen for correction of NLF contour deficiencies 
 
 
 
 
 
 
 
 
 
 
  
 
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Study Design
This is a prospective, long-term safety and effectiveness follow-up study. 
 
Subject 
Participation
A subject 
may be involved in the extension of the study 
from 
visit 
 to the final follow-up visit.
Enrollment
Written informed consent will be obtained before any study related procedure is 
performed. 
Inclusion criteria
The subjects must meet the following criteria to be eligible for the study:
1.
Subjects willing to comply with the requirements of the study and 
providing a signed written informed consent.
 
Exclusion criteria
The presence of any of the following exclusion criteria will exclude a subject
from enrollment in the study:
1.
Any medical condition that, in the opinion of the 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).
2.
Other condition preventing the subject from entering the study in the 
Investigator’s opinion, 
 
 
 subjects anticipated to be unavailable or incapable of 
understanding the study assessments.
3.
Participation in any interventional clinical study throughout the duration 
of the study.
Investigational 
product, reference 
product, dose, 
mode of 
administration and 
location of treated
area
 
Treatment
Study Procedures
Effectiveness Assessments:

 
 
 
 
  
 
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
 
 
Evaluation of Safety:

AEs will be obtained from signs and symptoms reported by the subject or 
detected during each examination visit to obtain information about any 
medical occurrence that meets the definition of an AE.
 
Any subject with a treatment related AE that is ongoing at the time of study 
completion will be followed until that AE is resolved or stabilized.  Any AE 
assessed as related to the study product 
 with onset after 
subject participation in the study is over, and that the Investigator becomes aware 
of should be reported to the Sponsor.
Study Report
A study report will be compiled at the conclusion of the study.
Schedule of Events
Statistical Methods
 
 
 
 
 
 
  
 
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Abbreviations and Definitions of Terms
AE
Adverse event
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
CIP
Clinical Investigational Plan
CRF
Case report form
CRO
Contract research organization
CTA
Clinical trial agreement
CTN
Clinical trial number
CV
Curriculum vitae
DMP
Data management plan
eCRF
Electronic case report form
FDA
United States Food and Drug Administration
First treatment
Initial injection of study product
GCP
Good Clinical Practice
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
ICF
Informed Consent Form
ICH
International Conference on Harmonisation
IFU
Instructions for use
 
 
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
MedDRA
Medical dictionary for regulatory activities
Nasolabial Fold (NLF)
Lines between the nose and the corner of the mouth
  
 
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PI
Principal Investigator; qualified person responsible for conducting the study at 
a study site
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
SAE
Serious Adverse Event
SDV
Source Data Verification
SOC
System Organ Class
SOE
Schedule of Events
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 products
The investigational products and the reference product under study
Study site
Institution or site where the study is carried out
 
 
WHO
World Health Organization
  
 
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Table of Contents
Study Administrative Structure _____________________________________________________________2
Sponsor Signatures_______________________________________________________________________3
Synopsis _______________________________________________________________________________4
Abbreviations and Definitions of Terms ______________________________________________________7
Table of Contents ________________________________________________________________________9
List of Tables___________________________________________________________________________11
List of Figures _________________________________________________________________________11
1
Ethical Considerations____________________________________________________________12
1.1
Statement of ethical compliance__________________________________________________12
1.2
Application to Institutional Review Board and/or Regulatory Authorities _______________12
2
Background Information__________________________________________________________12
2.1
Indication and population description_____________________________________________12
2.2
Study product Profile __________________________________________________________12
2.2.1
Investigational product description _______________________________________________12
2.2.1.1
Non-clinical documentation ________________________________________________12
2.2.1.2
Clinical documentation____________________________________________________12
2.3
Study rationale and justification for design ________________________________________13
2.4
Risks and benefits _____________________________________________________________13
3
Objectives and Endpoints _________________________________________________________13
3.1
Safety objective and endpoints ___________________________________________________13
3.2
Effectiveness objective and endpoints _____________________________________________13
4
Design of the Study ______________________________________________________________14
4.1
General outline________________________________________________________________14
4.2
Number of subjects ____________________________________________________________14
4.3
Duration of subject participation_________________________________________________14
4.4
Randomization and blinding_____________________________________________________14
4.4.1
Randomization_______________________________________________________________14
4.4.2
Blinding____________________________________________________________________14
4.4.3
Emergency Unblinding ________________________________________________________14
4.5
Medical history________________________________________________________________14
4.6
Prior and concomitant therapies _________________________________________________14
4.6.1
Definition __________________________________________________________________14
4.6.2
Categories __________________________________________________________________15
4.6.3
Recording __________________________________________________________________15
4.6.4
Authorized concomitant therapies________________________________________________15
4.6.5
Prohibited concomitant therapies ________________________________________________15
4.7
Visits ________________________________________________________________________17
  
 
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5
Subjects ________________________________________________________________________19
5.1
Subject information and informed consent_________________________________________19
5.2
Inclusion criteria ______________________________________________________________19
5.3
Exclusion criteria______________________________________________________________19
5.4
Screening and subject number ___________________________________________________19
5.5
Withdrawal of subjects _________________________________________________________19
6
Study Products __________________________________________________________________20
6.1
Investigational product _________________________________________________________20
6.2
Additional study supplies _______________________________________________________20
6.3
Treatment____________________________________________________________________20
7
Safety Assessments_______________________________________________________________20
7.1
Assessment of AEs by direct questioning of subject and evaluation of subject ____________20
7.2
Adverse events ________________________________________________________________21
7.2.1
Definition of an adverse event___________________________________________________21
7.2.2
Definition of a serious adverse event _____________________________________________21
7.2.3
Recording instructions_________________________________________________________21
7.2.3.1
Intensity _______________________________________________________________22
7.2.3.2
Causal relationship and seriousness __________________________________________22
7.2.4
Reporting of adverse events ____________________________________________________22
7.2.5
Reporting of serious adverse events ______________________________________________22
7.2.6
Follow-up of ongoing related events after termination of the study and eventswith onset after 
termination of study (subject last visit) __________________________________________________23
7.2.7
Reporting and follow-up of events occurring after subject termination of the study _________23
7.2.8
Pregnancy __________________________________________________________________24
7.2.9
Anticipated adverse events _____________________________________________________24
8
Effectiveness Assessments _________________________________________________________24
9
Data Handling and Management ___________________________________________________29
9.1
Data management _____________________________________________________________29
9.2
Electronic case report forms_____________________________________________________29
9.2.1
Data entry __________________________________________________________________29
9.2.2
The query process ____________________________________________________________29
9.2.3
User identification____________________________________________________________30
9.2.4
Audit trail __________________________________________________________________30
9.3
Source documents _____________________________________________________________30
9.4
Record keeping and access to source data__________________________________________30
  
 
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9.5
Document and data retention ____________________________________________________31
10
Statistical Methods_______________________________________________________________31
10.1
General ______________________________________________________________________31
10.2
Analysis populations ___________________________________________________________31
10.3
Demographics, baseline assessments, and subject characteristics ______________________31
10.4
Effectiveness analysis___________________________________________________________31
10.5
Safety analysis ________________________________________________________________32
10.6
Handling of missing data________________________________________________________32
10.7
Withdrawal and deviations______________________________________________________32
10.8
Sample size ___________________________________________________________________33
11
Protection of personal data ________________________________________________________33
12
Quality Control and Quality Assurance _____________________________________________33
12.1
Quality control ________________________________________________________________33
12.2
Quality assurance______________________________________________________________33
12.3
Changes to the Clinical Investigational Plan________________________________________34
13
Financing, Indemnification, and Insurance___________________________________________34
14
Publication Policy________________________________________________________________34
15
Suspension or Premature Termination ______________________________________________34
16
References______________________________________________________________________35
17
Appendices _____________________________________________________________________36
List of Tables
List of Figures
List of Appendices
  
 
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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.
 
 
2.2
Study product Profile
2.2.1
Investigational product description
  
 
 
 
2.2.1.2
Clinical documentation
Please refer to the Sculptra Aesthetic Instructions for Use (IFU) document. 
 
 
 
  
 
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2.3
Study rationale and justification for design
 
The purpose of this extension of the study is to evaluate 
long-term safety and effectiveness data of Sculptra Aesthetic
 
 
2.4
Risks and benefits
No treatment is administered in this study; hence, there are no risks to participate. 
The benefit is better knowledge about the safety profile for Sculptra Aesthetic 
 
 
3
Objectives and Endpoints
3.1
Safety objective and endpoints
Safety Objective
The objective is to evaluate the long-term safety of Sculptra Aesthetic
 
 
Safety endpoint

Incidence, intensity, time to onset and duration of adverse events (AEs) collected throughout the 
study period. 
3.2
Effectiveness objective and endpoints
The objective is to evaluate the long-term effectiveness of Sculptra Aesthetic
 
Effectiveness endpoints
 
 
 
 
 
 
 
  
 
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4
Design of the Study
4.1
General outline
This is a 
prospective, open-label follow-up study, with aim to evaluate the long-term safety and 
effectiveness of treatment with Sculptra Aesthetic for correction of NLF contour deficiencies. 
 
 
Figure 1. Study Flow Chart
4.2
Number of subjects
Approximately 60 
4.3
Duration of subject participation
A subject may be involved in the study for approximately 
the final follow-up
visit.
End of study is when all enrolled subjects have completed all visits or were prematurely discontinued 
from the study.
4.4
Randomization and blinding
4.4.1
Randomization
No randomization is needed in this study.
4.4.2
Blinding
No blinding is needed in this study.
4.4.3
Emergency Unblinding
Not applicable as the Investigator is unblinded.
4.5
Medical history
Medical history is captured in the pivotal study, hence not applicable for this extension study.
4.6
Prior and concomitant therapies
4.6.1
Definition
Therapies are defined as medications, treatments and procedures.
Concomitant therapies are defined as follows:
  
 
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4.6.2
Categories
The following three categories are to be considered for concomitant therapies:

Drugs/therapies including but not limited to 
 
 

Medical and surgical procedures including, but not limited to 
 

 
 
 
 
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 
4.6.5
Prohibited concomitant therapies 
 
 
 
 
 
 
 
 
  
 
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
 
 
 
  
 
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4.7
Visits
 
 
 
 
 
 
 
  
 
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5
Subjects
5.1
Subject information and informed consent
The Investigator or his/her authorized designee must always use the IRB-approved subject information 
and informed consent form (ICF) and it must not be changed without prior discussion with the Sponsor 
and approval from the applicable IRB.
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 regardingall 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 on
his/her future medical care, treatment or benefits to which the subject is otherwise entitled. The
information shall be provided in a language clearly and fully understandable to the subject. The subject
shall be given sufficient time to read and understand the informed consent form and to consider 
participation in the study. Before any study-related activities are performed, the informed consent form 
shall be personally signed and dated by the subject and the Investigator or his/her authorized designee 
responsible for conducting the informed consent process.
All original signed informed consent forms shall be filed in the Investigator file. The subject shall be 
provided with a copy of the signed and dated informed consent form and any other written information.
The Investigator shall ensure that important new information is provided to new and existing subjects 
throughout the study.
5.2
Inclusion criteria
The subjects must meet the following criteria to be eligible for thestudy:
1.
Subjects willing to comply with the requirements of the study and providing a signed written 
informed consent.
 
5.3
Exclusion criteria
The presence of any of the following exclusion criteria will exclude a subject from enrollment in the
study:
1.
Any medical condition that, in the opinion of the 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).
2.
Other condition preventing the subject from entering the study in the Investigator’s opinion,
 
 
5.4
Screening and subject number
Prior to any study procedures being conducted, the subject must sign the informed consent form. 
 
 
5.5
Withdrawal of subjects
Each subject shall be advised in the informed consent form that the subject has the right to withdraw 
from the study at any time, for any reason, without prejudice. Subjects may alsobe discontinued from 
  
 
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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's discretion at anytime.
The withdrawal criteria are:
 
 
 
 
 
 
 
The reason and date for withdrawal shall be documented in the eCRF. When possible, an explanatory 
comment shall be added to further explain the reason for withdrawal. If withdrawal of a subject occurs 
during a regular study visit, the eCRF for that specificvisit shall be completed as far as possible.
If a subject is withdrawn from the study, all data collected until the time of withdrawal will be used in 
the analyses. Subjects who are withdrawn or discontinued from the study will not be replaced. For AEs 
still ongoing at the time of withdrawal, see section 7.2.6.
6
Study Products
No study products will be provided during this study.
6.1
Investigational product
No investigational product will be provided during this study.  
6.2
Additional study supplies
No additional study supplies will be provided during this study. 
6.3
Treatment 
No treatment will be given during this study.
7
Safety Assessments
7.1
Assessment of AEs by direct questioning of subject and evaluation of subject
Safety assessments for this study include
 
 
 
  
 
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It is the responsibility of the 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 7.2.4.
 
7.2
Adverse events
7.2.1
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 personsI, whether or not related to 
the study product.
This definition includes:

events related to the investigational product or the reference product

events related to the procedures involved
7.2.2
Definition of a serious adverse event 
A serious adverse event (SAE) is an AE that:

led to death,

led to serious deterioration in the health of the subject, that either resulted in

a life-threateningII illness or injury, or

a permanent impairment of a body structure or body function, or

in-patient or prolonged hospitalizationIII, or

medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function,

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 anexpected 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 7.2.5).
I For users or other persons, this definition is restricted to events related to the investigationalproduct.
II 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).
III Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, withoutserious deterioration in 
health, is not considered a SAE. (Source:ISO14155:2011).
7.2.3
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 study entry. 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
  
 
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detected during each examination, observations made by the study site personnel, or spontaneous reports 
from the subjects or their relatives.
Exceptions from AE reporting are normal fluctuations in pre-existing diseases. However,pre- existing 
illnesses that deteriorates (in intensity or frequency) shall be reported asAEs.
7.2.3.1
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 thatday shall be
recorded.
7.2.3.2
Causal relationship and seriousness
 
 
 
 
7.2.4
Reporting of adverse events
Adverse event reporting on each subject shall start upon enrollment (singing of the informed consent) in 
the study. 
The reporting shall continue during each follow-up visit (including any telephonecontacts and extra 
visits between planned visits) until the last scheduled visit in the study.
All AEs, non-serious as well as serious, are to be reported as an AE in the eCRF.
7.2.5
Reporting of serious adverse events
The Investigator shall report any SAE to the Contract Research Organization (CRO) immediately but 
not later than24 hours of awareness of the event.  This initial report can be made via e-mail or submitted 
via the eCRF.
In case of difficulty to obtain all the required information within 24 hours, an initial report can be 
submitted, with the following information as a minimum, irrespective of whether some of it is regarded 
as preliminary:
  
 
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Follow-up information and data missing in the initial SAE reporting shall be gathered assoon as 
possible and reported to the CRO immediately but not later than 24 hours of awareness of the new data. 
Complete and adequate information on each SAE is required. All attempts to obtain this information, 
including dates for follow-up activities, must be documented bythe Investigator or designated study
staff.
Supporting documentation to be provided with the SAE report:

Concomitant therapies form/list

AE form/list

Medical history form/list

Study treatment CRF form

Any other relevant supporting documentation (e.g. hospital notes, death certificate, autopsy 
reports etc.)
E-mail for SAE reporting: 
The SAE form must be signed and dated by the Investigator. If the initial 24-hour SAEreport 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 as noted above. A copy of the fully completed SAE form shall be kept at the site.
In addition, the Investigator shall report SAEs to the responsible IRB without undue delay. The 
Investigator is responsible for checking what reporting procedures are applicable for his/her IRB 
regarding SAEs and final reportof the outcome of the study and to comply with such reporting 
procedures during the study period. For non-urgent complementary information not possible to send by 
e-mail, please use surface mail.
The Sponsor is responsible for reporting to the RA, if applicable and according to national regulations.
7.2.6
Follow-up of ongoing related events after termination of the study and events with 
onset after termination of study (subject last visit)
All serious as well as non-serious AEs with a causal relationship to the investigational 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.
7.2.7
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.
 
 
  
 
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7.2.8
Pregnancy
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
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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 handling eCRFs 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 
eCRF. 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. SAEs 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 subject and all 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 has been completed with all authorized investigation site personnel prior to the 
pivotal study being initiated and any data being entered into the system for any subject. Appropriate 
training and security measures with any potential new investigation site personnel will be completed 
prior to their involvement in the study.
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.
9.2.1
Data entry
All data shall be entered in English. The eCRFs should always reflect the latestobservations on the 
subjects participating in the study. Therefore, every effort 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 thedata 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 
  
 
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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 studysite 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 changeshall 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 tothe 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. These 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.
All supportive documentation submitted with the eCRF, such as laboratory or hospital records, shall be 
clearly identified with the CTN and subject number. Any personal information, including name, shall be 
removed or rendered illegible to preserve individual confidentiality.
9.4
Record keeping and access to source data
The Investigator/Institution shall permit study-related monitoring, audits, IRB review, and RA 
inspections and shall provide direct access to the source data/medical record including the identity of all 
participating subjects (sufficient information to link records, i.e. eCRF, medical records, original signed 
informed consent forms and detailed records of study product accountability). The records shall be 
retained by the Investigator as required bylocal legislation and international guidelines. Any transfer of 
responsibility for storage of the records shall be documented and the Sponsor shall be informed in
writing.
The Sponsor shall verify that each subject has consented in writing to direct access to the original 
medical record/source data (by the use of written subject information and signed informed consent). The 
data recorded in the eCRFs will be checked for consistency with the source documents/medical record 
by the monitor during monitoring (source dataverification; SDV). In order to be able to perform SDV, 
information about each subject’s participation in the study has to be detailed in the medical record.
  
 
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9.5
Document and data retention
All records pertaining to the conduct of the study, including signed eCRFs, informedconsent forms, 
study product accountability records, source documents, and other study documentation must be retained 
for as long as is specified in the CTA. Measures shall be taken to prevent accidental or premature 
destruction of these documents (e.g. protection against damage and unauthorized access, preferably by 
storage in a fire-proof cabinet).
It is the Investigator’s responsibility to inform the Sponsor in writing if the Investigator fileis moved or 
if the responsibility for the documents is transferred to someone else.
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10.6
Handling of missing data
All effectiveness endpoints will be evaluated based on observed cases.
10.7
Withdrawal and deviations
All withdrawn subjects will be listed individually, including at least subject number, dateand reason for 
withdrawal, and last visit performed.
Subjects with CIP deviations will be listed individually, including subject number and observed 
deviation.
Deviations from the statistical plan will be documented in the statistical report.
  
 
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10.8
Sample size
11 Protection of personal data
All processing of personal data must be carried out in accordance with national legislation concerning 
the protection of personal data. The Institution and the Investigator are responsible for complying with 
all requirements pursuant to national legislation in whichthe Institution and the Investigator are located. 
The Sponsor will ensure that all requirementsfor data processing are fulfilled.
The Investigator understands that clinical studies  conducted  under an  IDE  are exempt from the  study 
subject identifier confidentiality provisions of the HealthInsurance Portability and Accountability Act of 
1996 (HIPAA), and the study subject should be made aware of this exception in the informed consent. 
The Institution and Investigator are jointly responsible for providing sufficient information to all 
subjects to enable them to give their informed consent not only to the participation in the investigation, 
but also to the processing of Personal Data. Such information includes information regarding the 
purposes of the processing, the length of time during which Personal Data will be stored, the right of
access to stored Personal Data and the right to correction or purging of incorrect or obsolete Personal 
Data. A subject may also withdraw his or her consent at anytime.
A subject who withdraws his  or  her  consent  to  the  processing  of  Personal  Data must be considered 
to have withdrawn from the investigation but the data collected until the consent was withdrawn may be 
used in the statistical analyses.
Authorized representatives from the Sponsor or a RA may visit the investigational site to perform 
audits/inspections, including source data verification, i.e., comparing data inthe subjects’ medical 
records and the eCRF. Data and information will be handled with strict confidentiality.
The study shall include collection and processing of personal data as specified in the Regulation (EU) 
2016/679 (General Data Protection Regulation, GDPR) on the protectionof 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.
12.2
Quality assurance
The study site may be subject to quality assurance (QA) 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 thatsufficient 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 
  
 
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procedures to be followed. All Investigators and other responsible personsshall be listed together with 
their function in the study on the signature and delegationlog.
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 CIP amendment. However, 
administrative changes may be documented in the Sponsor file without requiring a CIP 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.
 
 
 
 
 
 
 
 
 
 
 
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.
  
 
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16 References
  
 
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17 Appendices
 
 
 
 
 
  
 
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