A Study Comparing Hyaluronic Acid Effectiveness & Evaluating Cheek Results With Restylane
Phase: NA
Conditions: Cheek Augmentation
Sponsor: Galderma R&D

 
05DF2004: A Study Comparing Hyaluronic Acid Effectiveness & Evaluating Cheek Results with Restylane 
(CHEEKY Study) 
 
 
NCT04638816 
 
03Nov2020 

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Investigators and Study Administrative Structure
Further details on all participating investigators and the complete administrative structure of the 
study are found in the study files.
Sponsor:
Q-Med AB, part of the Galderma Group
Medical expert:
         
Global Head of Clinical 
Development:
         
Clinical Project Manager:
Statistician:
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OTC
Over-the-counter
PI
Principal Investigator; qualified person responsible for 
conducting the study at a study site
PIPEDA
Personal Information Protection and Electronic Documents Act
PP
Per protocol
PT
Preferred term
QA
Quality assurance
RA
Regulatory authority
Reference product
Medical device, therapy (e.g. active control), placebo or no 
treatment, used in the reference group in a study.
SAE
Serious adverse event
SDV
Source data verification
SOC
System organ class
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 the reference product under 
study.
Study site
Institution or site where the study is carried out.
Touch-up
Repeated injection to be performed after treatment, if 
necessary, to achieve optimal correction.
U-HCG
Urinary human chorionic gonadotropin
WHO
World Health Organization
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Table of Contents
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE
2
SYNOPSIS
3
ABBREVIATIONS AND DEFINITIONS OF TERMS
7
TABLE OF CONTENTS
9
LIST OF TABLES
12
LIST OF FIGURES
12
LIST OF APPENDICES
12
1.
ETHICAL CONSIDERATIONS
13
1.1
Statement of ethical compliance
13
1.2
Application to independent ethics committee and/or regulatory authorities
13
2.
BACKGROUND INFORMATION
13
2.1
Indication and population description
13
2.2
Study product profile
14
2.2.1
Non clinical documentation
14
2.2.2
Clinical documentation
14
2.3
Study rationale and justification for design
14
2.4
Risks and benefits
14
3.
OBJECTIVE(S) AND ENDPOINT(S)
15
3.1
Objectives and endpoints
15
3.1.1
Primary objective and endpoint
15
3.1.2
Secondary efficacy objectives and endpoints
15
3.1.3
Safety objective and endpoint
16
4.
DESIGN OF THE STUDY
16
4.1
General outline
16
4.2
Number of subjects
17
4.3
Duration of subject participation
17
4.4
Randomization and blinding
17
4.4.1
Randomization
17
4.4.2
Blinding
18
4.4.3
Emergency unblinding
18
4.5
Medical history
18
4.6
Prior and concomitant therapies
18
4.6.1
Definition
18
4.6.2
Categories
18
4.6.3
Recording
18
4.6.4
Authorized concomitant therapies
18
4.6.5
Prohibited concomitant therapies
19
4.7
Visits
19
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8.2.2
Definition of a serious adverse event
32
8.2.3
Recording instructions
32
8.2.4
Reporting of adverse events
34
8.2.5
Reporting of serious adverse events
34
8.2.6
Follow up of unresolved events ongoing at termination of the study
35
8.2.7
Reporting and follow up of events occurring after subject termination of the study
35
8.2.8
Pregnancy
35
8.2.9
Anticipated adverse events
36
8.3
Device deficiencies
36
8.3.1
Definition of a device deficiency
36
8.3.2
Recording instructions
36
8.3.3
Reporting of device deficiencies
36
9.
DATA HANDLING AND MANAGEMENT
37
9.1
Data management
37
9.2
Electronic case report forms
37
9.2.1
Data entry
38
9.2.2
The query process
38
9.2.3
User identification
38
9.2.4
Audit trail
38
9.3
Source documents
38
9.4
Record keeping and access to source data
39
9.5
Document and data retention
39
10.
STATISTICAL METHODS
39
10.1
General
39
10.2
Analysis populations
40
10.3
Demographics, baseline assessments, and subject characteristics
40
10.4
Efficacy analysis
40
10.4.1
Primary analysis
40
10.4.2
Secondary analysis
40
10.5
Safety analysis
41
10.6
Handling of missing data
41
10.7
Interim analysis
41
10.8
Withdrawals and deviations
41
10.9
Sample size
41
11.
PROTECTION OF PERSONAL DATA
41
12.
QUALITY CONTROL AND QUALITY ASSURANCE
42
12.1
Quality control
42
12.2
Quality assurance
42
12.3
Changes to the clinical study protocol
42
12.3.1
Amendments
42
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12.3.2
Deviations
43
13.
FINANCING, INDEMNIFICATION, AND INSURANCE
43
14.
PUBLICATION POLICY
43
15.
SUSPENSION OR PREMATURE TERMINATION
43
16.
REFERENCES
45
List of Tables
Table 1 Schedule of events .......................................................................................................20
Table 2 Study product description ............................................................................................26
List of Figures
List of Appendices
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8. Safety Assessments
The methods for collecting safety data include laboratory assessments (pregnancy test) (Section 8.1), 
assessments of AEs (Section 8.2) and device deficiencies (Section 8.3).
8.1
Laboratory assessments
Pregnancy Test: For all women of childbearing potential, a urine pregnancy test (U-HCG) will be 
performed prior to treatment at Visit 2 (Baseline and treatment, Day 1) and at Visit 3 (Optional 
touch-up treatment at 2 weeks), as applicable. The test result will be documented in the eCRF.
8.2
Adverse events
8.2.1
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 persons1, whether or not related 
to the study product.
This definition includes:
a) events related to the study product or the reference product
b) events related to the procedures involved
8.2.2
Definition of a serious adverse event
A serious adverse event (SAE) is an AE that:
a) led to death,
b) led to serious deterioration in the health of the subject, that either resulted in
1. a life-threatening2 illness or injury, or
2. a permanent impairment of a body structure or body function, or
3. in-patient or prolonged hospitalization3, or
4. medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function,
c) led to fetal distress, fetal death, or a congenital abnormality or birth defect
In cases of doubt, whether an AE fulfils a serious criterion or not, there should be a predisposition 
to report as a SAE rather than not report as such (see Section 8.2.5).
8.2.3
Recording instructions
Each subject should be questioned about AEs at each study visit following signing of informed 
consent. 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 
                                                
1 For users or other persons, this definition is restricted to events related to the study product.
2 The term “life-threatening” in the definition of “serious” refers to an event in which the patient was at risk of death at 
the time of the event; it does not refer to an event which hypothetically might have caused death if it were more 
severe. (Source: ICH-E2A clinical safety data management: definitions and standards for expedited reporting).
3 Planned hospitalization for a pre-existing condition, or a procedure required by the CSP, without serious 
deterioration in health, is not considered a SAE. (Source: ISO14155:2011).
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each examination or from a laboratory test, observations made by the study site personnel, subject 
diaries, or spontaneous reports from the subjects or their relatives.
Exceptions from AE reporting are normal fluctuations in pre-existing diseases. However, pre-
existing illnesses that deteriorate shall be reported as AEs.
When an AE is related to a device deficiency (refer to Section 8.3), including technical device 
malfunction, the AE shall be recorded on the AE form/module in the eCRF and the technical 
complaint shall be reported separately on the clinical study complaint form.
Investigators, or other study site personnel, shall record all AEs in the eCRF, including:
a) Event term (recorded in standard medical terminology and avoiding abbreviations)
b) Affected area
c) Start date (first day with symptoms)
d) Stop date (last day with symptoms)
e) Intensity (mild, moderate, or severe according to definition in Section 8.2.3.1)
f)
Seriousness (serious or not serious, according to definition in Section 8.2.3.2)
g) Causal relationship to study product or study product injection procedure (yes or no, 
according to definition in Section 8.2.3.2)
h) Action taken (none, medication treatment, non-pharmacological treatment, or other 
procedures/tests, subject withdrawn)
i)
Outcome of the AE (ongoing, recovered, recovered with sequelae, death, chronic/ stable, not 
recovered at the end of the study)
The AE form/module in the eCRF must be signed and dated by the Investigator.
8.2.3.1
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.
8.2.3.2
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?”
If any of these questions is answered Yes, the AE is considered related.
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Cases that led to fetal distress, fetal death or a congenital abnormality or birth defect are to be 
regarded as SAEs and shall be reported on the exposure in utero report form to the Sponsor 
immediately but no later than 24 hours after the Investigators awareness. These events shall be
handled as SAEs during data processing. Other complications during the pregnancy that are related 
to the pregnant woman and fulfils any serious criteria, such as pre-eclampsia requiring 
hospitalization, shall be reported and handled as SAEs. Elective abortions without complications 
shall not be reported as AEs.
8.2.9
Anticipated adverse events
Injection related AEs such as bruising, erythema, itching, swelling, pain and tenderness are 
anticipated. Information regarding anticipated AEs for Restylane Volyme and Restylane Lyft 
Lidocaine are included in the IFUs (co-packed with product).
8.3
Device deficiencies
8.3.1
Definition of a device deficiency
A device deficiency is defined as an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety4, or performance.
Note: Device deficiencies include malfunctions, use errors, and inadequate labelling.
8.3.2
Recording instructions
When a device deficiency is discovered, Part A of the clinical study complaint form shall be 
completed by the Investigator. 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 8.2.4 and 8.2.5). 
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.
8.3.3
Reporting of device deficiencies
E-mail for device deficiencies reporting:
Fax number for device deficiencies reporting:
                                                
4 Inadequacy of device safety refers to properties of the device which could have or have led to an AE.
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A device deficiency that led to a SAE and any device deficiency that could have led to a SAE shall 
be reported to the Sponsor within 24 hours after the Investigator’s awareness (for contact 
information, see Section 8.2.5). 
If the Investigator or the Sponsor assesses that the device deficiency could have led to a SAE the 
Sponsor is responsible for reporting the device deficiency to RA and the PI is responsible for 
reporting it to the IEC.
The deficient study product shall be kept by the study site until the Sponsor has confirmed whether 
the product shall be returned to Sponsor for further study or if it can be destroyed at the study site.
9. Data Handling and Management 
9.1
Data management
Data management based on GCP refers to the activities defined to achieve safe routines to enter 
clinical data information into a database, efficiently and avoiding errors. The data management 
routine includes procedures for database set-up and management, data entry and verification, data 
validation, and documentation of the performed activities including information of discrepancies in 
the process. The data management process will be described in detail in the data management plan 
(DMP).
The database, the data entry screens and program will be designed in accordance with the CSP and 
the CRF template. Data validation will be performed by computerized logical checks and manual 
review. Drugs and events will be coded in accordance with World Health Organization (WHO) Drug 
and medical dictionary for regulatory activities (MedDRA) dictionaries as specified in the DMP. 
Safety data (SAE and if applicable AE of special interest) in the clinical database will be reconciled 
against the data in the safety database.
When all efforts have been made to ensure that the data recorded in the eCRFs and entered in the 
database is as correct and complete as possible, the clinical database will be locked. Study data will 
be transferred to SAS datasets, which thereafter will be write-protected. Statistical analyses will be 
generated in SAS using data from the locked datasets.
9.2
Electronic case report forms 
An electronic data capture application, compliant with regulatory requirements for software 
validation will be used to collect, modify, maintain, archive, retrieve, and transmit study data. An
eCRF is required and shall be completed electronically for each screened subject (screening visit) 
and included subjects (subsequent visits).
The eCRF includes password protection and internal quality checks, such as automatic range checks, 
to identify data that appear inconsistent, incomplete, or inaccurate. Study data shall be entered 
directly from the source documents, which are to be defined at each site before inclusion of the first 
subject.
Authorized study site personnel designated by the PI shall complete data collection. Appropriate 
training and security measures shall be completed with all authorized investigation site personnel 
prior to the study being initiated and any data being entered into the system for any subject.
The study data is the sole property of the Sponsor and shall not be made available in any form to 
third parties, except for authorized representatives of appropriate RA, without written permission 
from the Sponsor. At the end of the study, electronic data are kept at the Sponsor and a copy 
(provided by the vendor) at the study site as part of the Investigator file.
Any delegation of collection of data shall be specified and recorded.
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9.2.1
Data entry
All data shall be entered in English. The eCRFs should always reflect the latest observations on the 
subjects participating in the study. Therefore, the eCRFs shall be completed as soon as possible 
during or after the subject’s visit. The subject’s identity must always remain confidential, i.e. the 
name and address of the subjects must not be registered in the eCRFs or in the database. The 
Investigator must verify that all data entries in the eCRFs are accurate and correct. If some 
assessments are not done, or if certain information is not available, not applicable or unknown, the 
Investigator shall indicate this in the eCRF. The Investigator shall electronically sign off the study
data. By signing, the Investigator takes responsibility for the accuracy, completeness, and legibility 
of the data reported to the Sponsor in the eCRF.
9.2.2
The query process
The monitor shall review the eCRFs and evaluate them for completeness and consistency. Each 
eCRF shall be compared with the respective source documents to ensure that there are no 
discrepancies between critical data. All entries, corrections, and alterations shall be made by the PI
or his/her authorized designee. The monitor cannot enter data in the eCRFs. Once study data have 
been submitted to the central server via the eCRF, corrections to the data fields will be audit trailed, 
meaning that the reason for change, the name of the person who made the change, together with 
time and date will be logged. Roles and rights of the site personnel responsible for entering study
data into the eCRF shall be determined in advance. If discrepant data is detected during review of 
the data, either by the Sponsor or by its representatives, the responsible data manager or monitor 
shall raise a query in the electronic data capture application. The query shall state the question or 
data to be changed and shall be resolved in the system by the PI or his/her authorized designee. The 
appropriate study site personnel shall answer the queries in the eCRF. This will be audit trailed by 
the electronic data capture application meaning that the name of study site personnel, time, and date 
is logged.
9.2.3
User identification
Electronic CRF records will be automatically appended with the identification of the creator, by 
means of their unique UserID. Specified records shall be electronically signed by the Investigator to 
document his/her review of the data and acknowledgement that the data are accurate. This will be 
facilitated by means of the Investigator’s unique UserID and password; date and time stamps will 
be added automatically at time of electronic signature. If an entry in an eCRF requires change, the 
correction shall be made in accordance with the relevant software procedures.
9.2.4
Audit trail
All changes will be fully recorded in a protected audit trail and a reason for the change shall be 
stated. Once all data have been entered, verified, and validated, the database will be locked.
9.3
Source documents
The eCRF is essentially considered a data entry form and does not constitute the original (or source) 
medical records unless otherwise specified. 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.
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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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