A Randomized, Evaluator-Blinded, Parallel, Comparator-Controlled Study to Evaluate the Safety and Effectiveness of GAL1704 for Cheek Augmentation and Correction of Midface Contour Deficiencies
Phase: NA
Conditions: Cheek Augmentation
Sponsor: Galderma R&D

A Randomized, Evaluator-Blinded, Parallel, Comparator-Controlled Study to Evaluate the Safety and 
Effectiveness of GAL1704 for Cheek Augmentation and Correction of Midface Contour Deficiencies 
NCT Number: NCT03700047 
28Aug2018 

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Investigators and Study Administrative Structure
Sponsor:
Q-Med AB, a Galderma affiliate
Galderma Research and Development, LLC
Medical expert:
Clinical Project Manager:
Study 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
BE
Blinded evaluator; site staff, qualified by training and experience, who 
performs subject assessments but is blinded to study treatment provided 
to the subject
CFR
Code of Federal Regulations
CIP
Clinical Investigational Plan
Childbearing 
Potential
A female (including pre-menopausal subjects) capable of becoming 
pregnant. This includes women on oral, injectable, IUD, or barrier 
methods of contraception; women whose partners have been 
vasectomized or whose partners have received or are using barrier
contraceptive devices.
CRF
Case report form
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
EOS
End of Study
ET
Early termination
FDA
United States Food and Drug Administration
FST
Fitzpatrick Skin Type
G
Gauge
GCP
Good clinical practice
HA
Hyaluronic acid
HIPAA
Health Insurance Portability and Accountability Act
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.
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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
IRE
Injection Related Events; events related to study product injection, 
documented by study subjects in the Subject Diary
ISO
International Organization for Standardization
ITT
Intention-to-treat
MedDRA
Medical dictionary for regulatory activities
NPS
Numeric Pain Scale
NSAID
Non-steroidal anti-inflammatory drugs
OUS
Outside US
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
SAE
Serious adverse event
SAP
Statistical Analysis Plan
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 product and any reference product under study
Study site
Institution or site where study activities are conducted and overseen by 
the Principal Investigator
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TC
Telephone Call
Tx
Treatment
UPT
Urine pregnancy test
WHO
World Health Organization
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Table of Contents
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE
2
SIGNED AGREEMENT OF THE CLINICAL STUDY PROTOCOL
4
SYNOPSIS
5
ABBREVIATIONS AND DEFINITIONS OF TERMS
19
LIST OF TABLES
25
LIST OF APPENDICES
25
1.
ETHICAL CONSIDERATIONS
27
1.1
Statement of ethical compliance
27
1.2
Application to independent ethics committee and/or regulatory authorities
27
2.
BACKGROUND INFORMATION
27
2.1
Target indication and population description
27
2.2
Investigational and comparator product description and treatment regimen
27
2.3
Previous experience
28
2.3.1
Clinical documentation
28
2.4
Study rationale
29
2.5
Justification for the design of the study
29
2.6
Risks and benefits
30
3.
OBJECTIVE(S) AND ENDPOINT(S)
30
3.1
Objectives and endpoints
30
3.1.1
Primary effectiveness objective and endpoint
30
3.1.2
Secondary effectiveness objectives and endpoints
31
3.1.3
Safety objectives and endpoints
32
3.1.4
Exploratory Objectives
32
4.
DESIGN OF THE STUDY
32
4.1
General Outline
32
4.2
Number of subjects
37
4.3
Duration of subject participation
37
4.4
Randomization and blinding
37
4.4.1
Randomization
37
4.4.2
Blinding
37
4.4.3
Emergency unblinding
38
4.5
Medical history
38
4.6
Prior and concomitant therapies
38
4.6.1
Definition
38
4.6.2
Authorized Concomitant Therapies
38
4.6.3
Prohibited Concomitant Therapies
38
4.7
Schedule of Events
40
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8.
SAFETY ASSESSMENTS
63
8.1
Assessment of AEs by direct question to subject and evaluation of subject
63
8.1.1
Adverse events of special interest
63
8.3
Pre-defined, expected, post-treatment events
64
8.5
Laboratory assessments
66
8.6
Adverse events
66
8.6.1
Definition of an adverse event
66
8.6.2
Definition of a serious adverse event
66
8.6.3
Recording instructions
67
8.6.4
Reporting of adverse events
68
8.6.5
Reporting of adverse events of special interest (AESIs)
68
8.6.6
Reporting of serious adverse events
69
8.6.7
Stopping Rule
70
8.6.8
Follow up of ongoing related events after termination of the study and events with onset after termination of 
study (subject last visit)
70
8.6.9
Pregnancy
70
8.6.10
Anticipated adverse events
71
8.7
Device deficiencies
71
8.7.1
Definition of a device deficiency
71
8.7.2
Recording instructions
71
8.7.3
Reporting of device deficiencies
72
9.
DATA HANDLING AND MANAGEMENT
72
9.1
Data management
72
9.2
Electronic case report forms
72
9.2.1
Data entry
73
9.2.2
The query process
73
9.2.3
User identification
73
9.2.4
Audit trail
74
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9.3
Source documents
74
9.4
Record keeping and access to source data
74
9.5
Document and data retention
74
10.
STATISTICAL METHODS
75
10.1
General
75
10.2
Analysis populations
75
10.3
Demographics, baseline assessments, and subject characteristics
76
10.4
Efficacy analysis
76
10.4.1
Primary effectiveness analysis (Group A only)
76
10.4.2
Secondary effectiveness analyses
76
10.4.3
Group B effectiveness success criterion
77
10.5
Safety analysis
77
10.6
Handling of missing data
77
10.7
Interim analysis
78
10.8
Data monitoring committee
78
10.9
Withdrawals and deviations
78
10.10
Sample size
78
11.
PROTECTION OF PERSONAL DATA
79
12.
QUALITY CONTROL AND QUALITY ASSURANCE
80
12.1
Quality control
80
12.2
Quality assurance
80
12.3
Changes to the clinical study protocol
80
13.
FINANCING, INDEMNIFICATION, AND INSURANCE
81
14.
PUBLICATION POLICY
81
15.
SUSPENSION OR PREMATURE TERMINATION
81
16.
REFERENCES
82
List of Tables
Table 1. Fitzpatrick Skin Types , .............................................................................................41
List of Appendices
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4.7
Schedule of Events
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3. in-patient or prolonged hospitalisation8, 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 foetal distress, foetal 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 study 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 8.5.5).
8.6.3
Recording instructions
AEs will be recorded once a subject is enrolled (i.e., randomized and/or treated) in the study. 
All other events that occur after the subject signs the ICF but before enrollment will be recorded 
in the subject’s medical history. Each AE should be fully recorded in the subject’s source 
document and the eCRF.  Beginning after initial treatment on Day 1, each subject should be 
questioned about AEs at each study visit. The question asked should be: “Have you had any 
health problems since receiving study treatment?” Information on AEs can also be obtained 
from signs and symptoms detected during each examination.  
When an AE is related to a device deficiency including technical device malfunction, the AE 
should be recorded in the AE eCRF and the technical complaint should be reported separately 
on the 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 8.6.3.1)
f)
Seriousness (serious or not serious, according to definition in Section 8.6.3.2)
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 events 
shall be collected daily by subjects in a Diary for up to 28 days after each treatment.
                                                
8 Planned hospitalisation for a pre-existing condition, or a procedure required by the CSP, without serious 
deterioration in health, is not considered a SAE. (Source: ISO14155:2011).
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8.6.3.1
Intensity
Intensity will be recorded for each reported AE. The following definitions of intensity are to 
be used:
Mild:
Awareness of symptoms or signs, but easily tolerated (acceptable)
Moderate:
Enough discomfort to interfere with usual activity (disturbing)
Severe:
Incapacity to work or to do usual activity (unacceptable)
If the intensity changes within one day, the maximum intensity of the AE during that day 
shall be recorded.
8.6.3.2
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 device injection procedure?”
If any of these questions is answered ‘Yes’, the AE is considered related.
Each AE will also be assessed for causal relationship and seriousness by the Sponsor, in order 
to fulfil regulatory requirements. 
8.6.4
Reporting of adverse events 
Adverse event reporting on each subject shall start upon enrollment (i.e., randomized and/or 
treated with study product) in the study. Any events that occur after the subject signs the ICF 
but before enrollment will be recorded in the subject’s medical history. The reporting shall 
continue during each follow-up visit (including telephone contacts and unscheduled visits) until 
the last scheduled visit in the study.
All AEs, non-serious as well as serious, are to be reported as an AE in the eCRF.
8.6.5
Reporting of adverse events of special interest (AESIs)
AESIs should be reported (using the AE Clarification Form) within 24 hours of awareness to 
the Sponsor/CRO at the email address
. In case of 
difficulty to obtain all the required information within 24 hours, an initial report can be 
submitted with follow up information provided within 24 hours of awareness of the new 
information.
The following information should be provided when reporting an AESI: 

Subject identification (subject number and initials)

Event description including observed symptoms
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If there is a pregnancy after the subject has been treated, the subject must continue to be 
followed and the outcome of pregnancy must be reported even if the delivery occurs after study
completion. Additional treatment with study product is not allowed once a pregnancy is noted.
A pregnancy confirmed during the study period after treatment must be reported by the 
Investigator on a pregnancy report form immediately upon acknowledgement and submitted to 
the Sponsor/CRO Safety email specified in section 8.6.5. The report can be prospective or 
retrospective. Follow-up shall be conducted to obtain outcome information on all prospective 
reports. 
Cases that led to foetal distress, foetal death, or a congenital abnormality or birth defect are to 
be regarded as SAEs and shall be reported on the exposure in utero report form to the Sponsor 
immediately but no later than 24 hours after the Investigator’s awareness. These events shall
be handled as SAEs during data processing. Other complications during the pregnancy that are 
related to the pregnant woman and fulfils any serious criteria, such as pre-eclampsia requiring 
hospitalization, shall be reported and handled as SAEs. Elective abortions without 
complications shall not be reported as AEs.
8.6.10 Anticipated adverse events
Information regarding anticipated AEs for the investigational product is included in the study-
specific Instructions for Use. For information regarding anticipated AEs for Juvéderm 
Voluma® XC (reference therapy) please refer to the manufacturer’s website (See Section 2.3.1).
8.7
Device deficiencies
8.7.1
Definition of a device deficiency
A device deficiency is defined as an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety9, or performance.
Note: Device deficiencies include malfunctions, use errors, and inadequate labelling.
8.7.2
Recording instructions
When a device deficiency is discovered, Part A of the clinical study complaint form shall be 
completed by the Investigator or qualified designee and entered into the eCRF. The type of 
complaint shall be described and injury to the subject or user or unintended exposure to study
product shall be reported as applicable. If an injury has occurred, an AE or an SAE form shall
be completed as applicable (refer to section 8.6.5). If no SAE was experienced as a result of 
the device deficiency, the Investigator shall assess whether or not the device deficiency could 
have led to an SAE if:

Suitable action had not been taken,

Intervention had not been made or,

Circumstances had been less fortunate
In Part B of the clinical study complaint form, the Sponsor will make the same assessment. 
                                                
9 Inadequacy of device safety refers to properties of the device which could have or have led to an AE.
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Authorized study site personnel designated by the Investigator 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 in a signature and delegation log.
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 effort should be made to complete 
the eCRFs within a reasonable time frame (for example, 3-5 working days) 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 on 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 authorised 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 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 authorised designee. The appropriate study site personnel shall
answer the queries in the eCRF within a reasonable timeframe (for example, 3 working days). 
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 CRFs will be automatically appended with the identification of the creator, by means 
of their unique User ID. 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 User ID and password; date and time 
stamps will be added automatically at time of electronic signature. If an entry in an eCRF 
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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.  These shall be made 
available for inspection by the monitor at each monitoring visit.  The Investigator must submit 
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 by local 
legislation and international guidelines.  Any transfer of responsibility for storage of the records 
shall be documented and the Sponsor shall be informed in writing.
The Sponsor shall verify that each subject has consented in writing to direct access to the 
original medical record/source data (by the use of written subject information and signed 
informed consent).  The data recorded in the eCRFs will be checked for consistency with the 
source documents/medical record by the monitor during monitoring (source data verification; 
SDV).  In order to be able to perform SDV, information about each subject’s participation in 
the study has to be detailed in the medical record. 
9.5
Document and data retention
All records pertaining to the conduct of the study, including signed eCRFs, informed consent 
forms, study product accountability records, source documents, and other study documentation 
must be retained for 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 file is 
moved or if the responsibility for the documents is transferred to someone else.
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16. References
N/A
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