A Randomized, Split-Hand, Subject-Blinded Study Comparing Pain, Safety and Effectiveness of Restylane Skinboosters Vital Lidocaine and Restylane Vital Without Lidocaine for Improved Appearance of the Dorsal Hand in Chinese Subjects
Phase: NA
Conditions: Skin Aging of Dorsal Hands
Sponsor: Galderma R&D

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Protocol number: 43CH2305
Clinical Study Protocol
A Randomized, Split-Hand, Subject-Blinded Study Comparing Pain, Safety 
and Effectiveness of Restylane Skinboosters Vital Lidocaine and Restylane 
Vital without Lidocaine for Improved Appearance of the Dorsal Hand in 
Chinese Subjects
Name of Investigational Medical Device: Crosslinked Sodium Hyaluronate Gel for Injection
Model & Specification： Restylane® Skinboosters™ Vital Lidocaine, 1mL/syringe
Whether it is the Class III medical device which needs clinical study approval from NMPA?  
Yes
 No
Leading Clinical Study Institution: Huashan Hospital, Fudan University
Coordinating Investigator:  
Sponsor：
Galderma SA
Zählerweg 10
6300 Zug
Switzerland 
Telephone: +41 76 352 2430
This study protocol contains confidential information belonging to Galderma SA. Except as may 
be otherwise agreed to in writing, by accepting or reviewing these materials, you agree to hold 
such information in confidence and neither disclose it to any third parties (except where required 
by applicable law) nor use it for any other purpose than in relation to the clinical study described 
herein. No information may be disclosed to any third party without prior written consent from 
Galderma SA.
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Table of Content
Protocol Synopsis..............................................................................................................................9
1
Sponsor’s Information..........................................................................................................19
1.1
Sponsor’s Name: .......................................................................................................19
1.2
Sponsor’s Address.....................................................................................................19
1.3
Sponsor’s Contact Information ...............................................................................19
2
The Information of Clinical Study Institutions and Principal Investigators ..................19
3
Background Information of Clinical Study........................................................................20
3.1
Background Information of Research and Development......................................20
3.2
Clinical Rational for Addition of Lidocaine in Restylane Vital............................20
3.2.1 Mode of Action and Performance .............................................................................21
3.3
Basic Information of Investigational Product ........................................................21
3.3.1
Description of the Device.....................................................................................21
3.4
Previous Clinical Study ............................................................................................21
3.5
Scope of Application and the Relevant Information .............................................23
3.5.1
Intended Purpose ..................................................................................................23
3.5.2
Indication and Target Population .........................................................................23
3.5.3
Intended Users......................................................................................................24
3.5.4
Contraindications..................................................................................................24
3.5.5
Warnings and Precautions....................................................................................24
4
Study Objectives ...................................................................................................................26
4.1
Primary Effectiveness Objective .............................................................................26
4.3
Safety Objectives.......................................................................................................27
4.4
Exploratory Objective ..............................................................................................27
5
Study Design..........................................................................................................................27
5.1
Overall of Study Design and Rationale...................................................................27
5.1.1
Overall Study Design ...........................................................................................27
5.1.2
Study Rationale ....................................................................................................28
5.2
Selection of Subjects .................................................................................................28
5.2.1
Inclusion Criteria..................................................................................................28
5.2.2
Exclusion Criteria.................................................................................................29
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5.2.3
Screening and Subject Numbers...........................................................................30
5.2.4
Withdrawal of Subjects ........................................................................................30
5.2.5
Duration of Subject Participation.........................................................................31
5.3
Effectiveness Assessments ........................................................................................31
5.3.1
Primary Efficacy Assessment:..............................................................................31
5.3.3
Basis of Efficacy Parameter Determination .........................................................32
5.4
Safety Assessments....................................................................................................33
5.4.1
Adverse Events (AEs) ..........................................................................................33
5.4.3
Basis of Safety Parameter Determination.............................................................35
5.5
Photography ..............................................................................................................35
5.6
Study Medical Device and Control Medical Device...............................................35
5.6.1
Study Medical Device (Investigational Product) .................................................35
5.6.2
Packaging, Labelling and Storage........................................................................36
5.6.3
Control Medical Device (Comparator Product) ...................................................36
5.6.4
Product Accountability.........................................................................................36
5.7
Study Procedures ......................................................................................................38
5.7.2
Study Execution....................................................................................................38
5.7.3
Instruction of Device Use.....................................................................................42
5.7.3.1 Assembly of needle to syringe for Restylane Skinboosters Vital Lidocaine .......42
5.7.3.2 Treatment Procedure for Restylane Skinboosters Vital Lidocaine ......................43
5.7.3.3 Treatment Area and Treatment Regimen for Restylane Skinboosters Vital 
Lidocaine.....................................................................................................................44
5.7.3.4 Post-treatment care...............................................................................................45
5.7.4
Instruction of Concomitant Treatment .................................................................45
5.8
Bias Control Measures .............................................................................................46
5.8.1
Randomization and Blinding................................................................................46
6
Statistical Consideration ......................................................................................................47
6.1
Sample Size Estimation ............................................................................................47
6.1.1
Calculation Formula, parameter value and its basis of determination, calculation 
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results. .........................................................................................................................47
6.1.2
Sample Size of Each Disease in the Study, and its Rationale (if applicable).......47
6.2
Analyzed Data Set.....................................................................................................47
6.3
Criteria of Subjects Excluded..................................................................................48
6.4
Statistical Methods....................................................................................................48
6.4.1
General .................................................................................................................48
6.4.2
Demographics, baseline assessments, and subject characteristics .......................48
6.4.3
Effectiveness Analysis..........................................................................................48
6.4.4
Safety Analysis.....................................................................................................49
6.5
Handling of Missing data and Abnormal Value ....................................................49
6.6
Interim Analysis........................................................................................................50
6.7
Data Monitoring Committee....................................................................................50
6.8
Withdrawals and Deviations....................................................................................50
7
Monitoring Plan....................................................................................................................50
7.1
Site Selection Visit.....................................................................................................50
7.2
Site Initiation Visit ....................................................................................................50
7.3
Routine Monitoring Visits........................................................................................51
7.4
Close-Out Visit ..........................................................................................................51
7.5
Remote Monitoring...................................................................................................51
7.6
Reporting ...................................................................................................................51
7.7
Adverse Event Monitoring.......................................................................................51
7.8
Audits and Inspections .............................................................................................51
8
Data Management.................................................................................................................51
8.1
Data Management.....................................................................................................51
8.2
Electronic Case Report Forms.................................................................................52
9
Analysis of Risks and Benefits.............................................................................................52
9.1
Potential Complications and Side Effects...............................................................53
9.1.1
Anticipated Injection-related Reactions ...............................................................54
9.1.2
Post-marketing Adverse Event Reporting............................................................54
10
Quality Control in Clinical Study........................................................................................55
10.1
Quality Control .........................................................................................................55
10.2
Quality Assurance.....................................................................................................55
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11
Ethics and Informed Consent in Clinical Study ................................................................56
11.1
Ethical Considerations..............................................................................................56
11.1.1
Statement of Ethical Compliance.........................................................................56
11.1.2
Application to Independent Ethics Committee and/or Regulatory Authorities....56
11.2
Informed Consent Process .......................................................................................56
11.2.1
Subject information and informed consent...........................................................56
12
Requirements on Adverse Events and Device Deficiency Reporting...............................57
12.1
Definition of Adverse Events and Reporting Requirements.................................57
12.1.1
Definitions of Adverse Events (AEs)...................................................................57
12.1.2
Recording Instructions..........................................................................................57
12.1.3
Intensity................................................................................................................58
12.1.4
Causal Relationship and Seriousness ...................................................................58
12.1.5
Reporting of Adverse Events................................................................................58
12.1.6
Follow-up of Unresolved Events after Study Termination and New Events after 
Study Termination ......................................................................................................59
12.1.7
Pregnancy .............................................................................................................59
12.1.8
Anticipated Adverse Events .................................................................................59
12.2
Device Deficiency ......................................................................................................59
12.2.1
Definition of Device Deficiency ..........................................................................59
12.2.2
Recording Instructions..........................................................................................60
12.2.3
Reporting Device Deficiency ...............................................................................60
12.3
Definition of Serious Adverse Events......................................................................60
12.4
Reporting Process, Contact Person Information ...................................................61
13
Requirements on Protocol Deviation and Protocol Amendments....................................62
14
Access to Source Data and Source Documents ..................................................................63
14.1
Source Documents.....................................................................................................63
14.2
Record Keeping and Access to Source Data...........................................................63
14.3
Document and Data Retention.................................................................................64
15
The Contents of Clinical Study Report...............................................................................64
16
Confidentiality.......................................................................................................................65
17
Responsibilities of Each Party .............................................................................................65
18
Any Other Information to be Specified ..............................................................................65
18.1
Financing, Indemnification, and Insurance............................................................65
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18.2
Publication Policy......................................................................................................66
18.3
Suspension or Premature Termination...................................................................66
References list .................................................................................................................................69
Appendix 1
Visual Analogue Scale (VAS)..............................................................................70
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Abbreviations list
AE
Adverse Event 
BOCF
Baseline observation carried forward
Co-ordinating 
Investigator
An Investigator assigned the responsibility for the coordination of 
Investigators at different centers participating in a multicenter study
CSP
Clinical Study Protocol
CTA
Clinical Trial Agreement
CTN
Clinical trial number
CV
Curriculum vitae
DBL
Database Lock
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
FAS
Full Analysis Set
FSFV
First Subject First Visit
G
Gauge
GCP
Good Clinical Practice
HA
Hyaluronic acid
ICF
Informed Consent Form
ICH
International Conference on Harmonisation 
IEC
Independent Ethics Committee
IFU
Instructions for Use
Investigational 
product
Medical device being assessed for safety or performance in a study. 
“Investigational product” is the same as “study device”, 
“investigational device”, or “investigational medical device”.
Institution
Any public or private entity or agency or medical or dental facility 
where clinical studies are conducted.
Investigator
The Principal Investigator or other qualified person, i.e. 
sub-Investigator, designated and supervised by the Principal 
Investigator at a study site to perform critical study-related 
procedures and/or make important study-related decisions as 
specified on the delegation log. 
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Investigator File
Essential documents relating to a clinical study as defined in GCP 
guidance document and maintained by the Investigator.
ISF
Investigator Site File, see above.
LSLV
Last Subject Last Visit
MedDRA
Medical Dictionary for Regulatory Activities
NMPA
National Medical Products Administration
NSAIDs
non-steroid anti-inflammatory drugs
PI 
Principal Investigator
PP
Per protocol
QA
Quality assurance
RA
Regulatory authority
PT
Preferred term
SAE
Serious adverse event
SAP
Statistical Analysis Plan
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.
TSE
Transmissible spongiform encephalopathy
TW
Thin Wall
U-HCG
Urinary human chorionic gonadotropin
VAS
Visual Analogue Scale
WHO
World Health Organization
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Protocol Synopsis
Clinical Study Title:
A Randomized, Split-Hand, Subject-Blinded Study Comparing Pain, Safety and 
Effectiveness of Restylane Skinboosters Vital Lidocaine and Restylane Vital 
without Lidocaine for Improved Appearance of the Dorsal Hand in Chinese 
Subjects.
Clinical Trial 
Number:
43CH2305
Indication:
The study products are intended for injection in the dorsal hand to improve its 
appearance by increasing the tissue volume in patients over the age of 18.
Study Population:
Subjects of Chinese origin, age ≥ 18 years, who are eligible for treatment to 
improve the appearance of the dorsal hand by increasing tissue volume.
Country(ies) Involved 
and 
Planned Number of 
Study Centers:
Country(ies): China
No. of Study Centers: 3
Total Number of 
Subjects (Planned): 
Approximately 90 subjects will be enrolled.
Clinical Study Design:
This is a randomized, multi-center, split-hand, subject-blinded study comparing 
pain, safety and effectiveness of Restylane Skinboosters Vital Lidocaine and 
Restylane Vital without lidocaine for improving appearance of the dorsal hands 
in Chinese subjects. 
Written informed consent will be obtained before any study related procedure is 
performed. Subjects will be screened for eligibility within 14 days prior to study 
randomization on Day 1. The Screening Visit and Baseline Visit can be 
performed on the same day.
Each subject will receive treatment on Day 1 with Restylane Skinboosters Vital 
Lidocaine® in one hand and Restylane Vital in the opposite hand, as randomly 
assigned. Study treatment will be unblinded for the Treating Investigator. The 
first injection will always start in the right hand. No topical or local anesthetic or 
other pain-relieving medication should be used before all Visual Analogue Scale 
(VAS) assessments are completed. Ice for pain relief is allowed and should be 
applied equally on both hands before treatment. Ice may also be used after all 
VAS evaluations have been completed, and an approximately two-minute ice 
application time per hand is recommended. The second treatment, that is the 
injections in the left hand, will be performed after the treatment of the first 
(right) hand and the VAS assessment at T0 of the right hand is completed. 
The subject will assess pain experienced directly after treatment on a 100 mm 
VAS at the end of each treatment (before massaging the treatment area). The 
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time should be recorded in the electronic Case Report Form (eCRF) and the pain 
will thereafter be assessed by the subject at 10±3, 20±3, and 30±3 minutes on 
the VAS after the treatment on the right and left hand, respectively.
After the treatment of each hand is finished, and after the T0 pain assessment is 
complete, massage can be performed on the treated area of that hand. It is 
recommended not to exceed five minutes of massage to avoid affecting 
subsequent VAS assessments. It is not necessary to massage both hands 
simultaneously.
A safety follow-up telephone call should be made 72 hours after treatment.
 
 
 
 
 
 
 
 
 
Primary Effectiveness 
Objective and 
Endpoint: 
To demonstrate that Restylane Skinboosters Vital Lidocaine is associated with 
less pain than Restylane Vital when injected in the dorsal hand for 
improvement of appearance.
Endpoint: The within-subject difference in VAS score (Restylane Skinboosters 
Vital Lidocaine - Restylane Vital) at end of injection (T0).
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Exploratory Objective 
and Endpoint: 
Not applicable
 
 
 
 
Clinical Study 
Duration:
From First Subject First Visit (FSFV) to LSLV (Last Subject Last Visit) 
throughout the study interval: approximately 16 weeks; including:
•
12 weeks enrollment
•
2 weeks screening
•
2 weeks follow-up after treatment
Inclusion Criteria:
1. Signed and dated informed consent to participate in the study
2. Chinese origin
3. Age at least 18 years
4. The subject is willing and able to comply with the requirements of the 
study and agrees to adhere to the visit schedule and to be compliant to 
the study instructions
5. Subjects eligible for treatment to improve appearance of the dorsal 
hand by increasing tissue volume 
6. Same grade of tissue degeneration and need for treatment in both 
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hands
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Exclusion Criteria:
1. Any previous non-permanent or permanent implant/filler in the 
hands, including autologous fat
2. Any mesotherapy or resurfacing procedure (laser, chemical peels or 
other ablative or non-ablative treatment) in the hands within 6 months 
prior to baseline
3. Any previous hand surgery including sclerotherapy
4. Any fibrosis or scarring or deformities on the hands
5. Advanced photoaged/ photodamaged skin (e.g. advanced skin 
elastosis, multiple lentigo solaris lesions) or skin condition with very 
crinkled or fragile skin on the dorsal hands
6. Subjects with active skin disease, inflammation or related conditions in 
the hand
7. Subjects with a history of precancerous (e.g. actinic keratosis) or 
cancerous lesions in the hands
8. Subjects with a history of Raynaud´s disease or phenomenon, or 
history of other disease that may affect peripheral circulation
9. History of neurological disease that may affect peripheral neurological 
function
10. Subjects with a history of autoimmune disease or joint disease or 
connective tissue disease (e.g. rheumatoid arthritis, lupus, scleroderma 
etc)
11. Subjects with known hypersensitivity to any ingredient of the study 
product or anesthesia used in the study or with a history of any 
significant Adverse Events caused by dermal fillers
12. Use of topical retinoids on the dorsal hands within 6 weeks prior to 
baseline or use of systemic retinoids within 6 months prior to baseline
13. History of chronic lymph edema or breast cancer /mastectomy with 
potential to cause edema
14. Concomitant thrombolytic or anticoagulant therapy and therapy with 
inhibitors of platelet aggregation, (e.g. non-steriod anti-inflammatory 
drugs, acetylsalicylic acid, Omega 3 and Vitamin E) within 2 weeks 
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prior 
to 
treatment, 
or 
a 
history 
of 
bleeding 
disorders. 
Cyclooxygenase-2 (COX-2) inhibitors are allowed.
15. Treatment 
with 
chemotherapy, 
immunosuppressive 
agents, 
immunomodulatory therapy (e.g. monoclonal antibodies), systemic or 
topical (dorsal hands) corticosteroids (inhaled corticoids are allowed) 
within three months before study treatment
16. History of untreated epilepsy or other significant medical conditions
17. Women who are pregnant or breast feeding, or Woman of childbearing 
potential who are not practicing adequate contraception or planning to 
become pregnant during the study period.
18. Subjects participating in another interventional clinical study within 30 
days of baseline
19. Subjects with unattainable expectation with regard to the aesthetic 
results of the treatment
20. Subjects who are involved in conducting the study (e.g. colleagues 
within the same department) or close relatives to any of the study staffs 
(e.g. parents, children, siblings or spouse ) as well as subjects who are 
employed by the Sponsor company, or close relatives of employees at 
the Sponsor company
21. Subjects with any other condition  which in the opinion of the 
Investigator, might compromise the subject’s ability to tolerate the 
injection procedure or comply with requirements of the study
Investigational 
Product:
Restylane Skinboosters Vital Lidocaine
Composition:

Crosslinked sodium hyaluronate 20 mg/mL

Lidocaine hydrochloride 3 mg/mL

Phosphate buffered saline q.s. ad 1 mL
Restylane Skinboosters Vital Lidocaine is supplied in a glass syringe, packed in 
a blister and outer carton. The product has a built in dose-guide, SmartClick 
System, which when activated creates a clicking sound and haptic feedback to 
indicate each injected dose. The 1 mL syringe gives approximately 100 such 
doses of 10 µL each. Disposable sterile 29G x ½” TW (thin wall) needles are 
co-packed with the study product.
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Comparator Product:
Restylane Vital
Composition:

Crosslinked sodium hyaluronate1 20 mg/mL

Phosphate buffered saline pH 7 ad q.s. 1 mL
1Produced from pharmaceutical grade sodium hyaluronate and crosslinking 
agent BDDE.
Restylane Vital will be provided in a glass syringe containing 1 ml of gel. The 
study sites will be provided with disposable sterile 29G x ½” TW needles for 
use in the study. 
Treatment area/ 
Treatment regimen/ 
Mode of 
administration:
The study product is intended for injection in the dorsal hand. Disposable 29G x 
½” TW needles should be used for both study products. Study product should be 
injected in the dermal layer of the skin, preferably in the deeper part of dermis. 
Allowed injection techniques are; multipuncture or short linear. Inject slowly 
while pulling the needle backwards. 
No more than 20 µL should be injected per injection point when using the 
multipuncture technique. Slowly inject 20 µL droplets in the dermal layer of the 
skin, spacing droplets 0.5-1.0 cm apart to cover the entire treatment area. 20 µL 
equals to 2 clicks when injecting with the smart click function activated on the 
Restylane Skinboosters Vital Lidocaine syringe. 
The volume for each treatment should be adjusted depending on the subject’s 
need and a volume of 0.5-1 mL for one hand per treatment session will be 
allowed. The same volume should be used for both hands.
Treatment Blinding
To ensure the subject is kept treatment-blind the following measures are to be 
employed at the study site when injecting:
-
The same injection techniques, volume per injection point and similar 
total volume should be used for both hands as described above.
-
At the discretion of the investigator, the subject can listen to white 
noise/music in headphones during the treatment to cancel out the click 
sounds from the syringe when injecting Restylane Vital Skinboosters 
Lidocaine.
-
The injection will be performed behind a screen to prevent the subject 
from seeing the type of syringe used in order to achieve subject 
blinding.
Post-treatment care
No topical or local anesthetic or other pain-relieving medication should be used 
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before all VAS assessments are completed. 
Ice for pain relief is allowed after all VAS evaluation is completed. 
If any irregularities are noted after the use of ice pack, the treated area can be 
massaged again. A cream can be used during massage at the discretion of the 
investigator.
The subjects will be asked to avoid intensive physical stress (training) or 
intensive manual activities involving the hand, extensive heat (sauna)/sun or 
extreme cold in the first 2 days after the treatment .
The subjects will also be asked to avoid extensive exposure to potential skin 
irritants (e.g. cosmetics or laundry detergent) that could affect the skin in the 
treated area before the skin has healed completely in order to prevent infections.
Effectiveness 
Assessments: 

Pain assessment by Visual Analogue Scale (VAS)
 
Safety Assessments:

Adverse Events (AEs)
Other Assessments:

Pregnancy Test

Photography
Statistical Method:
In general, all effectiveness, safety and baseline characteristics variables will be 
presented using descriptive statistics and graphs as appropriate. Continuous data 
will be summarized by descriptive statistics n (number of observations), mean, 
standard deviation, median, minimum and maximum value, while categorical 
data will be presented by number of subjects and percentage.
Primary analysis
The primary endpoint in this study is defined as the within-subject difference 
in VAS score (Restylane Skinboosters Vital Lidocaine - Restylane Vital) at 
the end of injection. The null hypothesis (H0) that the within-subject difference 
in VAS is greater than or equal to 0 mm will be tested against the alternative 
hypothesis (H1) that the within-subject difference in VAS is less than 0 mm 
using a one-sample t-test. More formally, the following statistical hypotheses 
will be tested, with the within-subject difference denoted by ∆:
 
If the one-sided p-value of the test is <0.025, the pain at the end of injection 
will be considered statistically significantly lower after treatment with 
Restylane Skinboosters Vital Lidocaine than after treatment with Restylane 
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Interim Analysis:
Not applicable – no interim analysis is planned to be performed in this study.
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1
Sponsor’s Information
1.1 Sponsor’s Name: 
Galderma SA 
1.2 Sponsor’s Address
Zählerweg 10
6300 Zug
Switzerland
1.3 Sponsor’s Contact Information
Sponsor’s Contact Information:
Name, Address, Contact 
information and relevant 
certifications of Agent
2
The Information of Clinical Study Institutions and Principal 
Investigators
The final list of sites participated in the study will be filed in the study files.
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3
Background Information of Clinical Study
3.1 Background Information of Research and Development
Among the different materials used as raw materials in injectable fillers for aesthetic use, sodium 
hyaluronate, also denoted hyaluronic acid when found in vivo and hereinafter referred to as HA, is 
the most frequently used.1 Hyaluronic acid is a naturally occurring polysaccharide found in all 
vertebrates and in some bacteria.1,2 The chemical structure of HA is very simple with repeating 
disaccharide units of glucuronic acid and N-acetylglucosamine. As the chemical structure of HA is 
identical in all species and tissues, it is non-allergenic. 
To eliminate the risk for transmitting diseases between closely related species (i.e. transmissible 
spongiform encephalopathy; TSE), the HA used in the manufacture of HA gels in Restylane Vital 
is of non-animal source, biosynthesised from Streptococcus species of bacteria.
During manufacturing, cross-links are introduced between the HA chains using the NASHA™  
technology in order to obtain a gel network. As a result, the duration of the gel in the body is 
several months, as compared to only a few days for a solution of native HA.
Restylane Vital is injected in the skin to improve its appearance by increasing the tissue volume. 
The mode of action is based on the physical effects of the gel when integrated in the skin. The 
effects originate from the ability of crosslinked hyaluronic acid to bind water. Restylane Vital will 
degrade gradually in the body. With degradation the effect will disappear. The patients, who want 
to keep the effect can receive follow-up treatment when the effect becomes less visible or 
disappears. In a clinical study conducted in China, the effect remained at least 3 months after the 
initial injection in most patients. These subjects were injected with Restylane Vital in the dorsal 
hand three times 4 weeks apart. 
Restylane Vital indicated for dorsal hands to improve its appearance by increasing the tissue 
volume in patients over the age of 18 has been approved in China since Dec 2019. This study is 
initiated to assess if Restylane Skinboosters Vital Lidocaine provides a pain-relieving effect 
comparing to Restylane Vital without lidocaine. 
3.2 Clinical Rational for Addition of Lidocaine in Restylane Vital
From a historical point of view it’s worth mentioning that incorporation of lidocaine in collagen 
based dermal fillers to improve treatment comfort was introduced already in the 1980s. As the 
collagen based dermal fillers position as industrial standard for dermal fillers was replaced by 
hyaluronic acid based dermal fillers in the mid 1990s, the interest of incorporating lidocaine into 
those products to enable an improved treatment comfort has been present.
Restylane Vital, similar to other dermal fillers, is injected into the dermis. Clinical study data has 
demonstrated that injections in the dermis and the subcutaneous fat with the addition of lidocaine 
provide a more comfortable treatment due to pain reduction.3,4
Pain experienced during treatment with dermal fillers can be attributed to pain generated during 
the initial space occupation of the gel and therefore the addition of lidocaine reduces pain from 
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skin penetration of needle or cannula. In addition, there are indications from the literature that 
lidocaine has an inhibitory effect on proinflammatory as well as pain-mediating substance.5,6 
During an initial expansion of the tissue, as is the case when injecting and depositing the gel, a 
tension pressure occurs until the surrounding tissue has adjusted to the gel deposit. A rapid 
expansion of the tissue as well as the insertion of the needle cause damage in the tissue with 
transient release of proinflammatory and pain-mediating substances, which contributes to 
anticipated injection related reactions such as tenderness, redness, pain (including burn) and 
swelling. 
Added ancillary lidocaine in the injected gel has thus some capacity to counteract this effect and 
thereby a potential to give increased post treatment comfort, including decreased overall treatment 
associated pain and post treatment pain. The clinical finding of improved treatment comfort with 
the addition of lidocaine has led Galderma SA to evaluate the beneficial effect of adding lidocaine 
to Restylane Vital.
3.2.1 Mode of Action and Performance
Restylane Skinboosters Vital Lidocaine is injected in the skin to improve its appearance by 
increasing the tissue volume. The mode of action is based on the physical effects of the gel when 
integrated in the skin. The effects originate from the ability of crosslinked hyaluronic acid to bind 
water. Restylane Skinboosters Vital Lidocaine will degrade gradually in the body. With 
degradation the effect will disappear. The patients, who want to keep the effect can receive 
follow-up treatment when the effect becomes less visible or disappears. 
3.3 Basic Information of Investigational Product
3.3.1
Description of the Device
Restylane Skinboosters Vital Lidocaine is an injectable, sterile, transparent, biodegradable gel of 
non-animal crosslinked sodium hyaluronate. Restylane Skinboosters Vital Lidocaine has the 
addition of lidocaine hydrochloride. They are supplied in a glass syringe. The products have a built 
in dose-guide, SmartClick System, which when activated creates a clicking sound and haptic 
feedback to indicate each injected dose. The 1 mL syringe gives approximately 100 such doses of 
10 µL each. The contents of the syringe are sterilized using moist heat. The products are for single 
patient and single session use only. Disposable 29G needles sterilized using ethylene oxide are 
provided. 
3.4 Previous Clinical Study
Restylane Vital was approved for marketing in Europe 2004. It has been in clinical use in Asian 
population for many years, e.g. in Hong Kong (marketing approval 2007), Taiwan (marketing 
approval 2008) and South Korea (marketing approval 2009). Restylane Vital was approved for 
marketing indicated for dorsal hands in China in Dec 2019 based on a pivotal study 43CH1406.7 
Restylane® Skinboosters™ Vital Lidocaine is part of the Restylane family and is, similar to 
Restylane, manufactured using the NASHA Technology. The product obtained CE mark in 2004 
(without lidocaine) and in 2011 (with lidocaine) with the intended use to restore skin hydrobalance, 
improve skin structure and the elasticity of the skin.8
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As Restylane Skinboosters Vital Lidocaine is originally intended to rejuvenate the skin, it is 
believed to be suitable for the correction of wrinkles in areas with thin skin. The product is 
supplied in a glass syringe and has since 2014 a built-in dose-guide, the SmartClick™ injector 
system, which when activated permits controlled small injection volumes by creating a clicking 
sound to indicate each injected dose. The 1 mL syringe gives approximately 100 doses. Restylane 
Vital Lidocaine was the original brand names of the product and it was re-branded to Restylane 
Restylane Skinboosters Vital Lidocaine when introducing the integrated SmartClick injector 
system. 
The pain-relieving effect of lidocaine added to other Restylane products produced with the 
NASHA® Technology have been studied in several clinical investigations. It has been shown that 
the addition of lidocaine does not affect the intended performance of the product. Although the 
pain-relieving effect has not been studied in clinical investigations of Restylane Skinboosters, it is 
reasonable to assume that the addition of lidocaine will provide a pain-relieving effect similar to 
that demonstrated for other Restylane products.
There were 3 clinical studies investigating the effectiveness and safety of Restylane Vital 
Lidocaine so far:
Study 05DF1206 is an open, non-comparative study on the efficacy and safety of treatment of acne 
scars with Restylane Vital Lidocaine. In this study, 12 subjects were enrolled for treatment of acne 
scars and surrounding skin with up to 4 mL of Restylane Vital Lidocaine in 3 treatment sessions 
spaced 4 weeks apart. The findings demonstrated improvements in the appearance of atrophic, 
depressed, facial acne scars and in the quality of the surrounding skin following three treatment 
sessions of Restylane Vital Lidocaine. For the investigator-reported GAIS, 92% of the subjects 
were assessed to be at least somewhat improved at week 4 and from week 8 to 28, 100% of the 
subjects were improved. At week 36, 75% of the subjects were satisfied with the structure of the 
skin compared to 8% at baseline before treatment. In all cases, the satisfaction was increased from 
week 12, when the treatment regimen was completed, until study end. In terms of safety, eight 
subjects reported at least one AE that was assessed by the investigator to be procedure-related, and 
the most common AEs were implant site nodule and implant site redness, each event reported by 5 
subjects. All events resolved during the study. Subject diary data showed that the majority of 
subjects experienced injection-site reactions (such as bruising, redness, swelling, pain (including 
burn), tenderness, itching and bumps) after treatment. Frequency and severity of all symptoms 
decreased over time and the majority of the injection-site reactions were resolved within 14 days 
after each treatment session.9 
Study 05DF1211 is an evaluator-blinded, within-group, multi-center study of the effectiveness and 
safety of combined treatment with Azzalure, Restylane/Emervel fillers, and Restylane 
Skinboosters Vital Lidocaine compared with single treatment with either Azzalure alone (Group A) 
or Restylane/Emervel filler alone (Group B) in face. There were 61 subjects randomized (1:1) to 
either Group A or Group B. The study result revealed that the majority of subjects in the study 
population (83%) as well as in Group A (74%) and Group B (93%) separately, showed a superior 
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global facial aesthetic appearance after the first combined treatment compared to the single 
treatment as assessed by the blinded evaluator. A majority of subjects reported GAIS score 
improvement one month after single and combined treatments. All subjects had improved GAIS at 
Month 7 and Month 13 as assessed by the investigator. For safety, 27 subjects reported 48 AEs, 
out of which 41 were considered related to study product or injection procedure. These 41 events 
included bruising, hematoma, implant site inflammation, edema, swelling, and muscular weakness. 
All treatment-related AEs were resolved at study end except for two cases of muscle weakness 
after Azzalure injection. One Serious Adverse Event (SAE) (angina pectoris), considered unrelated 
to study product was reported.10 
Study 05DF1404, a randomized, multi-center, parallel-group, efficacy and safety study evaluating 
two and three initial treatment sessions of Restylane Skinboosters Vital Lidocaine (with the use of 
the SmartClick system) in the face in which 53 subjects were randomized in a 1:1 ratio to either 3 
(Group A) or 2 (Group B) initial treatment sessions showed that a majority of subjects (Group A: 
75%; Group B: 84%) were assessed as having superior facial aesthetic appearance at Month 3 after 
treatment compared to baseline by the blinded evaluator. Subject satisfaction questionnaires 
showed that subjects were more satisfied with the skin after treatment. Skin hydration was 
significantly increased compared to baseline at several time-points in both groups, while skin 
elasticity parameters showed some occasional (but not consistent) improvement after treatment. A 
total of 46 AEs in 17 subjects (65%) in Group A (3 initial treatment sessions) and 42 AEs in 14 
subjects (52%) in Group B (2 initial treatment sessions) were reported. Eight AEs in 4 subjects 
(16%) in Group A and 16 AEs in 5 subjects (19%) in Group B were assessed as related to the 
product or injection procedure. The most common related AE was implant site swelling with 5 
events in 2 Group A subjects (8%) and 6 events in 2 Group B subjects (7%); reported as mild in 
intensity. The reported related events were; bruising, swelling, discoloration, nodules, pain at 
injection site and abnormal skin texture. All events were resolved.11
Based on the clinical studies above, Restylane Vital Lidocaine (with a study including the use of 
the SmartClick system) used in face have shown to improve global aesthetic appearance as well as 
subject satisfaction, improvement in appearance of scars, skin hydration and elasticity. Overall, the 
completed clinical studies have shown that treatment of Restylane Vital Lidocaine in face is 
well-tolerated and safe. The majority of events reported after treatment with Restylane Vital 
Lidocaine in the face were injection-related, such as bruising, redness, swelling, pain (including 
burn) and hematoma. The reported events were mostly of mild to moderate character and resolved 
spontaneously without intervention. 
3.5 Scope of Application and the Relevant Information
3.5.1
Intended Purpose
Restylane Skinboosters Vital Lidocaine is for aesthetic use to improve appearance of dorsal hands. 
The addition of lidocaine provides a pain-relieving effect during treatment.
3.5.2
Indication and Target Population
This product is intended for injection in the dorsal hand to improve its appearance by increasing 
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the tissue volume in subjects over the age of 18. It should be injected in the dermal layer of the 
skin, preferably in the deeper part of dermis. The addition of lidocaine is intended to increase 
overall treatment comfort.
The products shall not be used in patients under 18 years of age.
3.5.3
Intended Users
Injections of Restylane Skinboosters Vital Lidocaine must only be done by plastic surgeons, 
dermatologists and cosmetic doctors at hospitals and medical plastic surgery institutions officially 
approved by the administrative authorities. These institutions include clinics for medical cosmetic 
and plastic surgery, dermatology departments, medical cosmetic outpatient departments and plastic 
surgery departments in general hospitals and specialized hospitals for medical cosmetic and plastic 
surgery, which must have obtained a ”Medical Institution Business License”.
3.5.4
Contraindications

Do not use in patients with severe allergies manifested by a history of anaphylaxis, or 
history or presence of multiple severe allergies.

Do not use in patients with a history of hypersensitivity to streptococcal proteins, as the 
product may contain trace amounts of such material.

Do not use in patients with known hypersensitivity to lidocaine or to amide-type local 
anaesthetics.
3.5.5
Warnings and Precautions
3.5.5.1 Warnings

Use at specific sites where there is active disease, such as inflammation (skin eruption 
such as cysts, pimples, rashes or hives), infection or tumours, in or near the intended 
treatment site should be avoided until the underlying process has been controlled.

Restylane Skinboosters Vital Lidocaine is only intended for use as an intradermal implant. 
The product should not be used for breast site injections.

This product must not be injected intramuscularly or intravascularly. Localized superficial 
ischemia and necrosis with potential scarring may occur after injection in or near vessels. 
It is thought to result from the injury, obstruction, or compromise of blood vessels. Special 
caution should be taken if the patient has undergone a prior surgical procedure in the 
planned treatment area. Areas with limited collateral blood flow have an increased risk of 
ischemia.

Unintentional intravascular injection may lead to embolization, thrombosis, occlusion of 
the vessels, ischemia, necrosis or infarction at the implant site or in the area supplied by 
the blood vessels affected. Stop the injection immediately if blanching occurs or if a 
patient complains of unusual pain or exhibits any symptoms suggestive of inadvertent 
intravascular injection. Patients should receive prompt medical attention and possibly 
evaluation by an appropriate specialist doctor should an intravascular injection occur.

Patients with bleeding disorders or patients using substances that affect platelet function, 
thrombolytics or anticoagulants may, as with any injection, experience increased bruising 
or bleeding at injection site.
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
Special care should be taken to avoid injection into tendons in the hand as it may weaken 
tendons and cause tendon rupture. 

This product should not be mixed with other products prior to injection
3.5.5.2 Precautions

Doctors are encouraged to discuss all potential risks of soft tissue injection with their 
patients prior to treatment and ensure that patients are aware of signs and symptoms of 
potential complications.

This product should only be used by doctors who have appropriate training, experience, 
and knowledge about the anatomy at and around the site of injection in order to minimize 
the risks of potential complications (perforation or compression of vessels, nerves and 
other vulnerable structures). 

Injection procedures are associated with a risk of infection. Aseptic technique and standard 
practice to prevent cross-infections are to be followed.

Use with caution in patients with risk factors for developing hand skin irritation.

Use in dorsal hand in patients with disease, injuries or disabilities of the hand has not been 
studied. Care should be used in treating patients with autoimmune disease affecting the 
hand, Dupuytren’s contracture, history of hand tumour, vascular malformations, 
Raynaud’s disease and patients at risk for tendon rupture.

Avoid injecting into areas with, or in close proximity to, prior implants other than sodium 
hyaluronate, as this could aggravate latent adverse events or interfere with the aesthetic 
outcome of the treatment.

Large bolus injection, injecting too superficially and injections in areas with limited soft 
tissue support or soft tissue cover, or thin skin, may result in contour irregularities and 
palpable lumps and/or bluish discolouration. 

Inflammatory pigmentation changes and scarring might occur following soft tissue 
injections. Patients with abnormal wound healing or dark skin (Fitzpatrick Type IV–VI) 
may be more prone to developing hypertrophic scarring and keloid formation. 

Injection procedures can lead to reactivation of latent or subclinical herpes viral infections.

This product should be used with caution in patients with autoimmune disease or on 
immunosuppressive therapy.

Patients with unattainable expectations are not suitable candidates for treatment. 

This product is packaged for single patient and single session use only and should be 
discarded immediately after use. Do not resterilize or reuse the product in order to avoid 
risks of infections.

Do not use the product if package is opened or damaged, or if the expiry date or lot 
number is illegible.

Patients should avoid excessive sun, UV lamp exposure and extreme temperatures at least 
until any initial swelling and redness have resolved. 

If laser treatment, chemical peeling or any other procedure based on active dermal 
response is performed after treatment with this product, there is a theoretical risk of 
eliciting an inflammatory reaction at the implant site. This also applies if the product is 
administered before the skin has healed completely after such a procedure.

The safety for use during pregnancy, in breastfeeding females or in patients under 18 years 
has not been established.
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Form (eCRF) and the pain will thereafter be assessed by the subject at 10±3, 20±3, and 30±3 minutes on the 
VAS after the treatment on the right and left hand, respectively.
After the treatment of each hand is finished, and after the T0 pain assessment is complete, massage can be 
performed on the treated area of that hand. It is recommended not to exceed five minutes of massage to 
avoid affecting subsequent VAS assessments. It is not necessary to massage both hands simultaneously.
A safety follow-up telephone call should be made 72 hours after treatment.
 
 
 
 
 
 
 
5.1.2
Study Rationale
Restylane Vital has been subject to a pivotal study confirming safety and efficacy of the product 
for the treatment of dorsal hands in Chinese populations. 
The pain-relieving effect of lidocaine added to other Restylane products produced with the 
NASHA® Technology have been studied in several clinical investigations, where the addition of 
lidocaine does not affect the intended performance of the product1-2. Therefore, it is reasonable to 
assume that the addition of lidocaine to Restylane Vital will provide a pain-relieving effect similar 
to that demonstrated for other Restylane products.
The study aims to evaluate the pain-relieving effect of Restylane Skinboosters Vital Lidocaine on 
aged skin on the dorsal hand compared to Restylane Vital.
5.2 Selection of Subjects
5.2.1
Inclusion Criteria
1.
Signed and dated informed consent to participate in the study
2.
Chinese origin
3.
Age at least 18 years
4.
The subject is willing and able to comply with the requirements of the study and 
agrees to adhere to the visit schedule and to be compliant to the study instructions
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5.
Subjects eligible for treatment to improve appearance of the dorsal hand by 
increasing tissue volume 
6.
Same grade of tissue degeneration and need for treatment in both hands
5.2.2
Exclusion Criteria
1.
Any previous non-permanent or permanent implant/filler in the hands, including 
autologous fat
2.
Any mesotherapy or resurfacing procedure (laser, chemical peels or other ablative or 
non-ablative treatment) in the hands within 6 months prior to baseline
3.
Any previous hand surgery including sclerotherapy
4.
Any fibrosis or scarring or deformities on the hands
5.
Advanced photoaged/ photodamaged skin (e.g. advanced skin elastosis, multiple 
lentigo solaris lesions) or skin condition with very crinkled or fragile skin on the 
dorsal hands
6.
Subjects with active skin disease, inflammation or related conditions in the hand
7.
Subjects with a history of precancerous (e.g. actinic keratosis) or cancerous lesions in 
the hands
8.
Subjects with a history of Raynaud´s disease or phenomenon, or history of other 
disease that may affect peripheral circulation
9.
History of neurological disease that may affect peripheral neurological function
10. Subjects with a history of autoimmune disease or joint disease or connective tissue 
disease (e.g. rheumatoid arthritis, lupus, scleroderma etc)
11. Subjects with known hypersensitivity to any ingredient of the study product or 
anesthesia used in the study or with a history of any significant Adverse Events 
caused by dermal fillers
12. Use of topical retinoids on the dorsal hands within 6 weeks prior to baseline or use of 
systemic retinoids within 6 months prior to baseline
13. History of chronic lymph edema or breast cancer /mastectomy with potential to cause 
edema
14. Concomitant thrombolytic or anticoagulant therapy and therapy with inhibitors of 
platelet aggregation, (e.g. non-steriod anti-inflammatory drugs, acetylsalicylic acid, 
Omega 3 and Vitamin E) within 2 weeks prior to treatment, or a history of bleeding 
disorders. Cyclooxygenase-2 (COX-2) inhibitors are allowed
15. Treatment with chemotherapy, immunosuppressive agents, immunomodulatory 
therapy (e.g. monoclonal antibodies), systemic or topical (dorsal hands) 
corticosteroids (inhaled corticoids are allowed) within three months before study 
treatment
16. History of untreated epilepsy or other significant medical conditions
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17. Women who are pregnant or breast feeding, or Woman of childbearing potential who 
are not practicing adequate contraception or planning to become pregnant during the 
study period.
18. Subjects participating in another interventional clinical study within 30 days of 
baseline
19. Subjects with unattainable expectation with regard to the aesthetic results of the 
treatment
20. Subjects who are involved in conducting the study (e.g. colleagues within the same 
department) or close relatives to any of the study staffs (e.g. parents, children, 
siblings or spouse ) as well as subjects who are employed by the Sponsor company, 
or close relatives of employees at the Sponsor company
21. Subjects with any other condition which in the opinion of the Investigator, might 
compromise the subject’s ability to tolerate the injection procedure or comply with 
requirements of the study
5.2.3
Screening and Subject Numbers
Each screened subject will be assigned a screening number consisting of “S” and the site number 
followed by a consecutive number starting with 01 at each site, e.g. S101, S102.The screening 
number shall be listed on a subject screening and inclusion log. 
A “screening failure” is defined as a subject who does not fulfil the eligibility criteria. For 
screening failures, the eCRF screening visit shall be completed to an extent that makes it clear 
which assessments have been made and the reason why the subject did not fulfil the eligibility 
criteria. The reason for excluding a subject from entering the study shall also be specified in the 
subject screening and inclusion log. 
When the Investigator has confirmed that all inclusion criteria and no exclusion criteria are met, 
each enrolled subject will be assigned a subject number by the eCRF consisting of the site number 
followed by a consecutive number starting with 01 at each site, e.g. 101, 102.
The subject number, subject name, and other information sufficient to link the eCRF to the 
medical records (e.g. national identification number, chart number, etc.) shall be recorded on a 
subject identification list. The subject identification list shall only be available at the site, both 
throughout and after the study.
5.2.4
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 also be 
discontinued from this study if the Investigator determines that it is in the subject’s best interest to 
do so, and may be withdrawn at the Investigator's discretion at any time.
The withdrawal criteria are:
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Medical reasons: If the subject suffers from a medical condition that in the judgement of the 
Investigator makes it medically necessary to withdraw the subject. The specific rationale for 
Investigator-initiated withdrawal of a subject for medical reasons shall document the specific 
condition for withdrawing the subject.
Withdrawal of informed consent: A subject can withdraw their consent to participate in the 
study at their own request or be withdrawn from participation in the study at the request of 
their legally authorised representative at any time for any reason.
Lost to follow-up: If a subject does not return for a scheduled visit, reasonable effort shall be 
made to contact that subject, e.g. call three times at different hours and leave messages if 
applicable before declaring the subject lost to follow-up.
Other: Examples of other reasons for withdrawal may be failure to comply with protocol 
requirements or to complete the protocol-specified evaluations.
The reason and date for withdrawal shall be documented in the eCRF. When possible, an 
explanatory comment shall be added in the study termination module/pages to further explain the 
reason for withdrawal. If withdrawal of a subject occurs during a regular study visit, the eCRF for 
that specific visit shall be completed as far as possible together with the study termination eCRF 
module. 
If withdrawal of a subject occurs between regular study visits the subject should when possible 
(irrespective of the reason for withdrawal) be scheduled for a termination visit. In these cases the 
eCRF for the early termination visit should be completed. The subject will need to follow the same 
requirements for the final visit.
If a subject is withdrawn from the study, all data collected until the time of withdrawal will be 
used in the analyses.
A withdrawn or discontinued subject must not be replaced or re-entered into the study.
If an AE which, according to the Investigator’s assessment, is related to the use of any of the study 
products and is still ongoing at the time of the withdrawal, such events shall be followed-up after 
the last study visit until resolved, assessed as chronic or stable, or for at least three months.
5.2.5
Duration of Subject Participation
The study subjects will be treated at the baseline visit and thereafter followed for 2 weeks. The 
total duration of participation in this study for each subject will be approximately up to 4 weeks.
5.3 Effectiveness Assessments
5.3.1
Primary Efficacy Assessment:
5.3.1.1 Pain assessment by Visual Analogue Scale (VAS)
The VAS is a subjective scale to measure pain intensity (Appendix 1). The subject shall be 
instructed to put a vertical mark, approximating the pain experienced after the procedure, on a 100 
mm horizontal line labelled “no pain” at the left end and “the worst pain you can imagine” at the 
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5.4.3
Basis of Safety Parameter Determination
Both AE and pre-defined expected post-treatment events evaluated in a subject diary have been 
widely adopted as safety parameters in many clinical studies of medical devices, including several 
trials sponsored by Galderma SA and its group companies and the pivotal study of Restylane Vital 
for the treatment of soral hands, 43CH1406Error! Reference source not found.,Error! Reference source not found..
5.5 Photography
Photographs will be taken at baseline, prior to the first injection of the study product and at the 
follow-up visit at Day 15. The baseline photographs were used for the assessment 
. The 
photographs could also be used to document AEs in the treatment area.
Camera equipment will be provided by the Sponsor and standardized photographs will be obtained 
according to detailed instructions in a separate photography user manual. Each hand will be 
photographed separately. Each Investigator and other study site personnel designated to take 
photographs, if applicable, shall be thoroughly trained in the equipment and techniques, and how 
to upload photographs to the secured web portal, if applicable, before study start. For further 
details, please see the instruction in photography user manual.
5.6 Study Medical Device and Control Medical Device
5.6.1
Study Medical Device (Investigational Product)
Restylane Skinboosters Vital Lidocaine
Restylane Skinboosters Vital Lidocaine is a sterile, transparent and biodegradable gel of 
crosslinked hyaluronic acid of non-animal origin with the addition of 0.3% lidocaine 
hydrochloride. It is supplied in a glass syringe with a luer-lock fitting. The product has a built in 
dose-guide, Smart Click™ System, which when activated creates a clicking sound and haptic 
feedback to indicate each injected dose. The 1 ml syringe gives approximately 100 doses of 10 µL 
each. The contents of the syringe are sterilized using moist heat. The exterior of the syringe, 
including finger grip and plunger rod are not sterile. The product is for single use only. Three 
disposable 29G TW (thin wall) needles, sterilized using ethylene oxide, are provided.
Composition:

Crosslinked sodium hyaluronate 20 mg/mL

Lidocaine hydrochloride 3 mg/mL

Phosphate buffered saline pH 7 ad q.s. 1 mL
Needle
Three disposable sterile 29G TW (thin wall) x ½ “ needles are provided. The size, length or wall 
thickness of the needle can affect the force needed to extrude the gel. The longer the needle is, and 
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the smaller the inner diameter is, the higher the resistance during injection and the higher the risk 
of leakage or separation of the needle from the syringe.
5.6.2
Packaging, Labelling and Storage
Restylane Skinboosters Vital Lidocaine manufactured by Q-Med AB, Sweden who will supply the 
study products. 
The syringe filled with Restylane Skinboosters Vital Lidocaine gel and the supplied needles are 
packed in a blister and put in a carton. The syringes are labelled with name of the product, name of 
the manufacturer (Q-Med AB). The carton will be labelled in local language, specifying the 
protocol number, lot number, expiry date and that the product is to be used for clinical studies 
exclusively.
Opened syringes should not be re-used. Accountability will be performed as specified in section 
5.6.4.
Restylane Skinboosters Vital Lidocaine should be stored up to 25° C. Protect from freezing and 
sunlight.
5.6.3
Control Medical Device (Comparator Product)
Restylane Vital
Restylane Vital will be provided in a glass syringe containing 1 ml of product. The study sites will 
be provided with 29 G needles Disposable sterile 29G x ½” TW needles for use in the study.
Composition:

Crosslinked sodium hyaluronate* 20 mg/mL

Phosphate buffered saline pH 7 ad q.s. 1 mL
*Produced from pharmaceutical grade sodium hyaluronate and crosslinking agent BDDE.
In terms of packaging, labelling, and storage of Restylane Vital, please see co-packed Restylane 
Vital Instructions for Use (IFU).
5.6.4
Product Accountability
The study product will be released to the PI or his/her authorised designee after study
approvals have been received from the IEC and the CTA has been signed by all parties.
The PI must ensure that the study products are kept in a secure location, with access limited to
those authorised by the PI.
The study product must be traceable from the manufacturer to its use in subjects until
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return or disposal. It is therefore important that the PI maintains accurate product
accountability records, i.e. documentation of the physical location of all study products,
deliveries, and return of study product between the Sponsor or a third-party vendor and the
PI, and documentation of administration of product to the subjects. A shipping record shall
be kept of all study products received from the Sponsor; including the product name, date
received, batch number, expiration date, and amount received. In addition, dispensing logs
shall be maintained including the product name, dispense date, the number of syringes
used, the number of syringes left in stock, and the subject receiving study product. A log for
accountability procedure is provided by the Sponsor.
When the study is completed, all unused or expired study product at each study site shall be
returned to the Sponsor or a third-party vendor for destruction. Any malfunctioning study
products shall be reported as described in the protocol.
Product deliberately or accidentally destroyed during shipment or at a study site shall be
accounted for and documented. Used syringes, disposable needle, and any opened unused
material must be discarded and must not be reused according to standard procedures at the
site. Disposal of hazardous material, i.e. syringes and needles must conform to applicable
laws and regulations. The study product must not be used outside the study.
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5.7 Study Procedures
5.7.1
Study Flowchart
5.7.2
Study Execution
5.7.2.1 General Outline
This is a randomized, multi-center, split-hand, subject-blinded, study comparing pain, safety and 
efficacy of Restylane Skinboosters Vital Lidocaine and Restylane Vital without lidocaine for 
improving appearance of the dorsal hands in Chinese subjects. 
5.7.2.2 Number of subjects
There will be approximately 90 subjects randomized to receive treatment with Restylane Vital on 
one hand and Restylane Skinboosters Vital Lidocaine on the other hand.
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5.7.2.4 Visit Description
Visit 1: Screening (Day -14 to 1)

The subject must be informed about the study both orally and in writing, and the Informed 
Consent Form must be signed before any study-related activity is performed.

The Investigator shall verify the inclusion and exclusion criteria for each subject (Section 
5.2).

All demographic and baseline assessments according to Section 5.7.2.5 shall be 
performed by the Investigator.

Record concomitant medications/procedures

The subjects shall be informed that they should try their best to use their usual hand 
skincare and cleaning procedures of the hands during the study.

For subjects who fail any of the inclusion or exclusion criteria, applicable parts of the 
screening visit eCRF should be completed, and the subject should be recorded as a 
screening failure in the Screening and Enrolment Log (Section 5.2.3) and in the eCRF.
Visit 2: Baseline Treatment (Day 1)

All demographic and baseline assessments according to Section 5.7.2.5 shall be 
performed by the Investigator.

The Investigator shall verify the inclusion and exclusion criteria for each subject (Section 
5.2.1 and 5.2.2).

The Investigator shall ask for any health problems since the last visit and any changes in 
hand skin care, concomitant medications or procedures performed. 

A pregnancy test (urinary human chorionic gonadotropin; U-HCG) shall be performed in 
subjects of childbearing potential. 

If the subject is still eligible for the study, the subject shall be randomized in accordance 
with the randomization procedure (Section 5.8.1).

For eligible subjects both hands will be treated with study products. The first injection 
will always start in the right hand. No topical or local anesthetic or other pain-relieving 
medication should be used before all VAS assessments are completed. Ice for pain relief 
are allowed and should be applied equally on both hands if used. 
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aseptic technique must be followed during the assembly procedure described below.
1)
Put on medical gloves.
2)
Use your thumb and forefinger to hold firmly around both the syringe-barrel and the 
luer-lock adapter part (C) of the closure system, see Picture below.
3)
With your other hand, take hold of the tip cap (A) at the end of the closure system and 
bend (do not rotate) until the cap disconnects and can be pulled off (tamper proof seal 
will be broken), see Picture below.
4)
Do not touch the syringe tip (B) to keep it sterile, see Picture below.
5)
Open the needle and grasp the needle shield.
6)
Assure to hold both the syringe barrel and the luer-lock adapter (C), see Picture below.
7)
To facilitate proper assembly, both push and rotate the needle firmly clockwise.
8)
Make sure the needle is screwed on all the way so that the needle shield touches the luer 
lock adapter (C), see Picture below.
9)
To remove the needle shield, hold the syringe and the luer lock adapter. With your other 
hand hold the needle shield and pull straight out. Do not rotate.
5.7.3.2 Treatment Procedure for Restylane Skinboosters Vital Lidocaine
1) Prior to treatment, a medical history should be obtained for proper patient selection. The 
patient shall be informed about the indications, precautions, treatment responses, potential 
adverse events, and advised to contact a healthcare professional if they experience anything 
unusual at the treatment area. 
2) Clean the treatment site thoroughly with a suitable antiseptic solution.
3) To avoid breakage of the needle, do not attempt to bend it before or during treatment. If the 
needle gets bent, discard it and complete the procedure with a replacement needle.
4) This product should be injected in the dermal layer of the skin, preferably in the deeper part of 
dermis. The injection technique and the administered quantity may vary. The multi puncture 
technique or short linear technique can be used. 
5) Before injecting, remove the air by pressing the rod carefully until a small droplet is visible at 
the tip of the needle. 
6) If desired, the Smart Click System is activated by pressing down the button located on the 
finger grip (D) until it locks into place, see Picture.
7) When the Smart Click System is switched on, again press the plunger rod carefully until the 
first click is heard to prime the system before use and to avoid a slightly larger volume of the 
first dose injected when the system is initially activated. The Smart Click System can be 
deactivated at any time by pushing the button in the finger grip upwards. It should be noted 
that it is not possible to perform an aspiration manoeuvre when the Smart Click system is 
activated.
8) When using the multi puncture technique it is recommended to inject approximately 20 μL 
(i.e. 2 clicks if the Smart Click System activated) per injection, 0.5 - 1 cm apart.
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9) The gel should be evenly distributed in the areas where treatment is needed.
10) Do not apply excessive pressure to the syringe at any time. Presence of scar tissue may impede 
advancement of the needle. If resistance is encountered the needle should be partially 
withdrawn and repositioned or fully withdrawn and checked for function.
11) If immediate blanching occurs, the injection should be stopped and the area massaged until it 
returns to a normal colour. Blanching may represent a vessel occlusion. If normal skin 
colouring does not return, do not continue with the injection.
12) It is recommended to change needle for each new treatment site or following multiple 
punctures to avoid use of blunt needles and minimize the risk of infections.
13) A too large volume or a too superficial injection may give bumps on the treatment site.
14) Treated areas can be gently massaged after the injection if any irregularities are noted.
5.7.3.3 Treatment Area and Treatment Regimen for Restylane Skinboosters Vital Lidocaine
The study product is intended for injection in the dorsal hand. Disposable 29G x ½” TW needles 
should be used for both study products. Study product should be injected in the dermal layer of the 
skin, preferably in the deeper part of dermis. Allowed injection techniques are; multipuncture or 
short linear. Inject slowly while pulling the needle backwards.
No more than 20 µL should be injected per injection point when using the multipuncture 
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technique. Slowly inject 20 µL droplets in the dermal layer of the skin, spacing droplets 0.5-1.0 cm 
apart to cover the entire treatment area. 20 µL equals to 2 clicks when injecting with the smart 
click function activated on the Restylane Skinboosters Vital Lidocaine syringe. 
The volume for each treatment should be adjusted depending on the subject’s need and a volume 
of 0.5-1 mL for one hand per treatment session will be allowed. The same volume should be used 
for both hands.
5.7.3.4 Post-treatment care
No topical or local anesthetic or other pain-relieving medication should be used before all VAS 
assessments are completed.
Ice for pain relief is allowed after all VAS evaluation is completed. 
If any irregularities are noted after the use of ice pack, the treated area can be massaged again. A 
cream can be used during massage at the discretion of the investigator.
The subjects will be asked to avoid intensive physical stress (training) or intensive manual 
activities involving the hand, extensive heat (sauna)/sun or extreme cold in the first 2 days after the 
treatment .
The subjects will also be asked to avoid extensive exposure to potential skin irritants (e.g. 
cosmetics or laundry detergent) that could affect the skin in the treated area before the skin has 
healed completely in order to prevent infections.
5.7.4
Instruction of Concomitant Treatment
Except as noted below, concomitant medications or other treatments or procedures may be utilized 
when the PI or his/her authorized designee considers it medically necessary.
Information regarding any use of concomitant medications, including over-the-counter 
medications administered during the study is to be recorded in the eCRF. The generic name or the 
trade name of all concomitant medication or a description of the procedure and the reason for its 
use shall be documented in the eCRF.
The following medications, treatments, and procedures are restricted or prohibited during the 
study:

Concomitant treatment with chemotherapy, immunosuppressive agents, 
immunomodulatory therapy (e.g., monoclonal antibodies) is prohibited.

Long term concomitant treatment with systemic or topical (on dorsal hands) corticosteroids 
are prohibited (inhaled corticoids are allowed). Corticosteroids should be used with caution 
and should be adjudged as necessary by the Investigator.

Use of systemic or topical (on the dorsal hands) retinoic acid is prohibited.

Planned hand surgery including sclerotherapy is prohibited.
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
Participation in any other clinical study within 30 days of baseline and during the study 
conduct is prohibited.
If a subject has used any of the above prohibited medications or performed any of the above 
prohibited procedures, a protocol deviation will be documented. The subject should continue in the 
study for the scheduled follow-up visits.
5.8 Bias Control Measures
5.8.1
Randomization and Blinding
5.8.1.1 Randomization
Approximately 90 subjects will be randomized to determine which hand to receive treatment with 
Restylane Skinboosters Vital Lidocaine, and Restylane Vital to the other hand. Before starting the 
study, a computer-generated randomization list will be prepared under the supervision of a 
designated statistician. 
Each subject will be assigned a subject number as they arrive for the treatment visit. 
Randomization will be assigned via the eCRF system. The treatment information will be kept by 
the Treating Investigator during the study not to be disclosed to the subjects.
5.8.1.2 Treatment Blinding
Only the subject will be blinded. Treating Investigator will not be blinded to the treatment 
assignment. 
The Treating Investigator is not allowed to discuss treatment assignment per hand with the 
subjects. All documents with information on study products shall be kept in a separate binder not 
available to the subjects.
To ensure the subject is kept treatment-blind the following measures are to be employed at the 
study site when injecting:
The same injection techniques, volume per injection point and similar total volume should be used 
for both hands as described above.
At the discretion of the investigator, the subject can listen to white noise/music in headphones 
during the treatment to cancel out the click sounds from the syringe when injecting Restylane Vital 
Skinboosters Lidocaine.
The injection will be performed behind a screen to prevent the subject from seeing the type of 
syringe used in order to achieve subject blinding.
5.8.1.3 Emergency Unblinding
Not applicable as the Treating Investigator is unblinded.
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6
Statistical Consideration
6.1 Sample Size Estimation
6.1.1
Calculation Formula, parameter value and its basis of determination, calculation results.
Several studies have been performed comparing the same HA-filler product with and without the 
addition of lidocaine or other analgesics. In the study 43CH15041, comparing Restylane for 
treatment of nasolabial folds with and without Lidocaine in subjects with Chinese ethnicity, the 
observed within-subject difference in VAS during injection was 33.0 mm with a standard 
deviation of 24.4 mm. In another study, in subjects with Chinese ethnicity, 43TW16282, 
comparing Restylane Perlane with and without Lidocaine, the mean within-subject difference in 
VAS at injection was 32.0 mm with a standard deviation of 19.5 mm.
However, due to the many injection points in the treatment of the hands, it is believed that the 
within-subject difference in VAS will be considerably less in this study than what was seen in the 
NLFs in the previous two studies referred to. Thus, assuming a true mean within-subject difference 
of -10 mm and a standard deviation of 25 mm, a significance level of 2.5% and using a one-sided 
one-sample t-test, inclusion of 68 subjects will give a power of 90% to reject the null hypothesis of 
>0 mm within-subject difference. To ensure sufficient power in the event of the need of a 
non-parametric test for the primary analysis, approximately 15% more subjects will be added to 
the 68 needed for the t-test. Hence, approximately 80 subjects will be needed for the primary 
analysis. In addition, a drop-out rate of 10% is assumed. Thus, approximately 90 subjects will need 
to be randomized in order to have at least 80 evaluable subjects for the statistical analysis.
6.1.2
Sample Size of Each Disease in the Study, and its Rationale (if applicable)
Not applicable
6.2 Analyzed Data Set
The following populations will be defined:

Safety
Includes all subjects who were injected in at least one 
hand. Subjects are analyzed based on the as treated 
principle.

Full Analysis Set (FAS)
Includes all subjects who were treated with Restylane 
Skinboosters Vital Lidocaine in one hand and Restylane 
Vital in the other hand. Subjects are analyzed according 
to the randomization assignment.

Per Protocol (PP) 
Includes all subjects in FAS that comply to the protocol 
procedures with no deviations considered to have a 
substantial impact on the evaluation of the primary 
variable.
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The FAS population is the primary population for all effectiveness analyses. All safety analyses 
will be based on the Safety population.
6.3Criteria of Subjects Excluded
For this study, the following protocol deviations that will exclude subjects from PP are identified 
(but not limited to):

VAS assessment at end of injection missing for at least one side

Study products not administered according to randomization

Any topical or local anesthetic or other pain-relieving medication used before all VAS 
assessments are completed

Significantly different injection volumes in left and right hand
6.4 Statistical Methods
6.4.1
General
A comprehensive Statistical Analysis Plan (SAP) with detailed description of all statistical 
analyses will be written and finalized prior to database lock (DBL). All statistical analyses, 
including summary tables and data listings, will be performed using the SAS® system (version 9.4 
or higher). 
Continuous variables will be summarized using standard statistical measures, such as mean, 
median, standard deviation, minimum and maximum values. Categorical variables will be 
presented in frequency tables with number and percent of observations for each level.
All confidence intervals will be two-sided and use the 95% confidence level. All statistical testing 
will be one-sided and performed at a significance level of 2.5% unless otherwise specified.
6.4.2
Demographics, baseline assessments, and subject characteristics
Demographic, baseline, and subject characteristics endpoints will be presented in total (or by study 
product where applicable) using descriptive statistics.
6.4.3
Effectiveness Analysis
6.4.3.1 Primary Analysis
The primary endpoint in this study is defined as the within-subject difference in VAS score 
(Restylane Skinboosters Vital Lidocaine - Restylane Vital) at the end of injection. The null 
hypothesis that the within-subject difference in VAS is greater than or equal to 0 mm will be 
tested against the alternative hypothesis that the within-subject difference in VAS is less than 0 
mm using a one-sample t-test. More formally, the following statistical hypotheses will be tested, 
with the within-subject difference denoted by ∆:
 
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As the design is intra-individual, in which the outcome of both treatments to be compared is 
available on each subject, it is expected that when a data is missing, it will be missing for both 
hands in most of the cases. A majority of the deviations to the protocol can be expected to affect 
both hands and evaluations of the same subject the same way. 
FAS analysis of VAS at the time of injection will impute a difference (Restylane Vital - Restylane 
Skinboosters Vital Lidocaine) of 0 mm as the primary method of imputation. This corresponds to 
assuming no pain relief using Restylane Skinboosters Vital Lidocaine compared to Restylane Vital 
and is considered as a worst case approach.
All other endpoints will be analyzed on available data, i.e. no imputations will be done.
To obtain an estimate of the true, clinical treatment effect, the primary effectiveness analysis will 
be performed using the PP. 
All other endpoints will be analyzed on available data, i.e. no imputations will be done.
6.6 Interim Analysis
No interim analysis is planned.
6.7 Data Monitoring Committee
Not applicable for this study.
6.8 Withdrawals and Deviations
All withdrawn subjects will be listed individually, including at least subject number, date and 
reason for withdrawal, and last visit performed.
Subjects with Clinical Study Protocol (CSP) deviations will be listed individually, including 
subject number and observed deviation. Depending on the seriousness of the deviation, subject 
might be excluded from the PP population, which shall be documented prior to DBL.
7
Monitoring Plan
A thorough and consistent monitoring plan will be implemented throughout this clinical trial in 
China to ensure data accuracy, participant safety, and adherence to the study protocol and 
regulatory requirements set by the National Medical Products Administration.
7.1 Site Selection Visit 
Before the initiation of the trial, a site selection visit will be conducted. The purpose of this visit is 
to assess the site's readiness, review the study protocol with the site's staff, and confirm the site's 
capabilities to perform the study in accordance with Good Clinical Practice (GCP) guidelines.
7.2 Site Initiation Visit
Once the site is selected, an initiation visit will be performed to review the protocol, the Case 
Report Forms (CRFs), and other relevant documents, and to train the study team on trial-specific 
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procedures.
7.3 Routine Monitoring Visits
The frequency of monitoring visits will be determined based on the complexity of the study, the 
rate of participant enrollment, and the site's performance. During these visits, the monitor will 
review the informed consent process, verify source data against CRFs, assess protocol compliance, 
check the adequacy of the site's investigational product storage and handling, and monitor adverse 
event reporting. 
7.4 Close-Out Visit
Upon completion of the study, a close-out visit will be performed to ensure all study activities 
have been completed, all data queries have been resolved, and the investigational product and 
study materials have been returned or appropriately disposed of.
7.5 Remote Monitoring
Depending on the circumstances, remote monitoring may also be performed to complement on-site 
visits.
7.6 Reporting
Monitors will generate a detailed report after each visit, which will document their findings, 
actions, and recommendations. These reports will be reviewed by the clinical trial management 
team to ensure continuous oversight and quality control. 
7.7 Adverse Event Monitoring
The clinical trial monitors will ensure that all adverse events are reported promptly, recorded 
accurately, and followed up appropriately in accordance with NMPA requirements.
7.8 Audits and Inspections
The study may be subject to audits performed by the Sponsor and inspections performed by the 
NMPA. These audits and inspections will review the study's compliance with the protocol, the 
GCP guidelines, and the regulatory requirements.
8
Data Management
8.1 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 
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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. 
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 
(SAEs and pregnancies) 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.
8.2 Electronic Case Report Forms 
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 will be 
transcribed 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 study 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 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 Analysis of Risks and Benefits
The primary potential benefit of Restylane Skinboosters Vital Lidocaine or Restylane Vital is an 
improvement in the skin quality and an increased subject satisfaction. Restylane Vital was 
approved for use in Europe 2004 with the indication to restore skin hydrobalance, improve skin 
structure and the elasticity of the skin. Restylane Vital indicated for dorsal hands to improve its 
appearance by increasing the tissue volume in patients over the age of 18 has been approved in 
China since Dec 2019, and is now regulatory cleared in more than 70 countries worldwide. The 
product is considered safe and effective for its intended use when injected in the dermal layer of 
the skin.
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In the pivotal study done in China, 43CH1406, Restylane Vital significantly improved skin quality 
conditions of the dorsal hand as assessed by a blinded evaluator. In addition, the treated hand had 
significantly better skin hydration and skin elasticity compared to the untreated control hand. The 
skin hydration and aesthetic appearance showed improvement throughout the whole 60-week 
study period.
Restylane Vital and Restylane Skinboosters Vital Lidocaine and all other injectable medical 
devices have the potential to cause complications. Most events are related to injected volume and 
injection technique, though some could be associated with properties or constituents of the 
substance itself.
In the pivotal study 43CH1406, the majority of the subjects reported anticipated injection-related 
reactions after the treatments. The most commonly reported injection-related reactions after the 
treatments were redness, bruising and, swelling. The majority of symptoms were mild in severity 
and most symptoms had onset within 1-2 days after injection. Median duration of symptoms was 
2-4 days. There was no increase in frequency, severity, or duration of injection-related reactions 
after repeated treatments in the same hand or treatment of the contralateral hand.
The majority of related adverse events (AEs) were mild or moderate in intensity and occurred after 
the third treatment. A few of the subjects reported AEs with delayed onset (>21 days after last 
treatment) including symptoms of injection/ implant site pruritus, injection site swelling, injection 
site pain, injection site discoloration, implant site redness, rash, folliculitis, and injection site 
nodule. All AEs with delayed onset were resolved at study completion for the respective subject. It 
was assessed that the reported AEs with delayed onset might be perceived as inflammatory 
reactions. Several of these subjects had occupational risk factors for developing hand skin 
irritation which might have contributed to the reactions. There were no serious or unexpected 
events reported related to the study product or injection procedure. 
However, given the anticipated low level of transient and acceptable AEs in connection with the 
injection, the risk-benefit assessment of the use of these products for the correction of the signs of 
aging appears to offer a clinical benefit at reasonable risk. Only Investigators qualified by 
education and experience and who are skilled in the use of dermal injections will be chosen to 
ensure proper device administration and management of study risk. 
Additional information about reported AEs and anticipated risks are included in the Investigators 
Brochure.
9.1 Potential Complications and Side Effects
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9.1.1
Anticipated Injection-related Reactions
Injection-related reactions (including bruising, redness, itching, swelling, pain (including burn) or 
tenderness at the implant site) might occur after treatment. Typically resolution is spontaneous 
within a few days after injection into the skin.
9.1.2
Post-marketing Adverse Event Reporting
The following post-marketing adverse events have been reported voluntarily from worldwide 
sources (non-exhaustive list) after treatment with Restylane Vital/Restylane Skinboosters Vital 
with or without Lidocaine (including hand and other treatment areas). The frequency of reporting 
is based on the number of estimated treatments performed with the products.
1/1 000 – 
1/10 000
Swelling/edema with immediate onset and onset up to several weeks after 
treatment.
1/10 000 – 
1/100 000
Papules/nodules, Mass/induration, Redness, Pain (including burn)/tenderness, 
Inflammation, Infection/abscess including purulent discharge and pustules, 
Bruising/bleeding, Ischemia/necrosis including pallor, livedo reticularis and 
vascular occlusion, Other injection site reactions and skin reactions including 
burning sensation, discomfort, irritation and warmth, Discoloration, Pruritus, 
Hypersensitivity/angioedema.
<1/100 000
Device ineffective, Scar/scab/skin atrophy, Granuloma/foreign body reaction, 
Asymmetry/deformity, Neurological symptoms including paresthesia and 
hyperesthesia, Urticaria, Blisters/vesicles, Rash, Eye disorders including ocular 
discomfort, increased lacrimation, eyelid ptosis and visual impairment, Acne, 
Dermatitis, Device dislocation, Capillary disorder such as telangiectasia, 
Encapsulation, Discharge, Reactivation of herpes infection, Muscle disorders 
such as muscle spasm, Non-dermatological events including pyrexia, headache 
discomfort and fatigue, Other dermatological events including dry skin, skin 
tightness and skin disorder.
When required, treatments for these events may include ice, massage, warm compress, 
nitroglycerine paste, corticosteroids, antibiotics, antihistamines, analgesics, antiviral agents, 
diuretic agents, aspiration/incision drainage, surgery or enzymatic degradation (with 
hyaluronidase) of the product.
Reports of serious adverse events are rare. The most commonly reported serious adverse events 
were ischemia/necrosis, infection/abscess, mass/induration and hypersensitivity. Other concurrent 
serious events included scarring and swelling.
Vascular compromise may occur due to an inadvertent intravascular injection or as a result of 
vascular compression associated with implantation of any injectable product. This may manifest as 
blanching, discoloration, necrosis or ulceration at the implant site or in the area supplied by the 
blood vessels affected; or in rare cases, as ischemic events in other organs due to embolization. 
Rare but serious cases of ischemic events associated with temporary or permanent vision 
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impairment, blindness, cerebral ischemia or stroke have been reported following facial aesthetic 
treatments. Treatments include anticoagulant, epinephrine, aspirin, hyaluronidase, corticosteroid 
treatment, analgesics, antibiotics, local wound care, drainage, hyperbaric oxygen and surgery.
Symptoms of inflammation at the implant site commencing either shortly after injection or after a 
delay of up to several weeks have been reported. In case of unexplained inflammatory reactions, 
infections should be excluded and treated, if necessary, since inadequately treated infections may 
progress into complications such as abscess formation. Treatment using only oral corticosteroids 
without concurrent antibiotic treatment is not recommended. The prolonged use of any medication, 
e.g., corticosteroids or antibiotics in treatment of adverse events should be carefully assessed, since 
this may carry a risk for the patient. In case of persistent or recurrent inflammatory symptoms, 
consider removal of the product by aspiration/drainage, extrusion or enzymatic degradation (use of 
hyaluronidase has been described in scientific publications). Before any removal procedure is 
performed, the swelling may be reduced by using a short course of corticosteroids, in order to 
palpate any remaining product more easily.
Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse 
events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to 
occur at the dermal filler treatment site following viral or bacterial illnesses or infections, 
vaccinations, or dental procedures. Typically, the reported inflammation was responsive to 
treatment or resolved on its own.
10 Quality Control in Clinical Study
10.1 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 CSP, subsequent amendment(s), GCP and the applicable regulatory requirements. 
Any CSP deviation shall be reported in the study, which shall be verified, discussed, and collected, 
by the monitor and appropriate corrective and preventive actions shall be taken. The PI is 
responsible for promptly reporting any deviations from the CSP that affects the rights, safety or 
well-being of the subject or the scientific integrity of the study, including those which occur under 
emergency circumstances, to the Sponsor as well as the Independent Ethics Committee (IEC) if 
required by national regulations. Deviations shall be reviewed to determine the need to amend the 
CSP or to terminate the study. 
10.2 Quality Assurance
The study site may be subject to quality assurance audit by the Sponsor as well as inspection by 
appropriate regulatory authority (RA). It is important that the PI and other relevant study site 
personnel are available during the monitoring visits, possible audits, and inspections, and that 
sufficient time is devoted to the monitoring process.
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It is the responsibility of the PI to ensure that all personnel involved in the study are fully informed 
of all relevant aspects of the study, including detailed knowledge of and training in all procedures 
to be followed. All Investigators and other responsible persons shall be listed together with their 
function in the study on the signature and delegation log.
11 Ethics and Informed Consent in Clinical Study
11.1 Ethical Considerations
11.1.1 Statement of Ethical Compliance
The study shall be conducted in compliance with the Clinical Trial Agreement (CTA), the Clinical 
Study Protocol (CSP), applicable Good Clinical Practice (GCP), and applicable regional or 
national regulations. The international standard for clinical study of medical devices for human 
subjects, ISO14155:2011 shall be followed. The International Conference on Harmonisation (ICH) 
guideline for GCP (E6) shall be followed as applicable for medical device. The study shall be 
conducted in accordance with the ethical principles that have their origin in the Declaration of 
Helsinki.
11.1.2 Application to Independent Ethics Committee and/or Regulatory Authorities
It is the responsibility of the Principal Investigator (PI) to obtain approval of the 
CSP/CSP amendment(s) from the IEC. The study shall not begin until the required favorable 
opinion from the IEC has been obtained. The PI shall file all correspondence with the IEC in the 
Investigator file and copies of IEC approvals shall be forwarded to the Sponsor. Any additional 
requirements imposed by the IEC or RA shall be followed. 
The collection, access to, processing, and transfer of protected health information or sensitive 
personal data shall be carried out in accordance with applicable rules and regulations.
11.2 Informed Consent Process
11.2.1 Subject information and informed consent
The PI or his/her authorized designee must always use the IEC-approved subject information and 
Informed Consent Form and it must not be changed without prior discussion with the Sponsor and 
approval from the applicable IEC.
It is the responsibility of the PI or his/her authorized designee to give each subject prior to 
inclusion in the study, full and adequate verbal and written information regarding all aspects of the 
clinical study that are relevant to the subject’s decision to participate throughout the study, e.g. 
explain the purpose and procedures of the study, the duration and number of expected participants, 
possible risks involved, and the opinion of the IEC. 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 
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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 PI or his/her authorized designee responsible for conducting the 
informed consent process. The consent includes information that data will be collected, recorded, 
processed, and transferred to countries outside China. The data will not contain any information 
that can be used to identify any subject.
All 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.
12 Requirements on Adverse Events and Device Deficiency Reporting
12.1 Definition of Adverse Events and Reporting Requirements
12.1.1 Definitions of Adverse Events (AEs)
An AE is any untoward medical occurrence, unintended disease or injury, or untoward clinical 
signs (including abnormal laboratory findings) in subjects, users or other persons*, 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
*For users or other persons, this definition is restricted to events related to the investigational product
12.1.2 Recording Instructions
AE will begin to be collected after ICF signed. Each subject will be questioned about AEs at each 
clinical visit following the screening visit. The question asked will be "Since your last clinical 
visit have you had any health problems?" Information on AEs can also be obtained from signs and 
symptoms detected during each examination or from a laboratory test, observations by the study 
personnel, subject diaries or spontaneous reports from the subjects. 
When an AE is related to a device deficiency (refer to section 12.2), including technical device 
malfunction, the AE shall be recorded on the AE module in the eCRF and the technical complaint 
shall be reported separately on the clinical study complaint form.
Investigators, or other study personnel, will record all AEs in the eCRF, including:

Event term (recorded in standard medical terminology and avoiding abbreviations),

Description of event and affected area (if applicable),

Start date (First day with symptoms)
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
Stop date (Last day with symptoms)

Intensity (mild, moderate or severe according to definition in section 12.1.3)

Seriousness (serious or not serious, according to definition in section 12.3)

Causal relationship to study product and study product injection procedure (yes or no)

Action taken (none, medication treatment, non-pharmacological treatment or other 
procedures/ tests, subject withdrawn)

Outcome of the AE (ongoing, resolved, resolved with sequelae, death)
The AE module in the eCRF must be signed and dated by the Investigator.
12.1.3 Intensity
For each reported AE, the intensity will be recorded. The following definitions of intensity are to 
be used:
Mild:
A mild AE means awareness of symptoms or signs, but easily tolerated 
(acceptable).
Moderate:
A moderate AE means enough discomfort to interfere with usual activity 
(disturbing).
Severe:
A severe AE means incapacity to work or to do usual activity 
(unacceptable).
If the intensity changes over time the maximum intensity of the AE should be recorded.
12.1.4 Causal Relationship and Seriousness
Each AE, serious as well as non-serious, will 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) will be used for 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. 
Each AE will also be assessed for causal relationship and seriousness by the Sponsor, in order to 
fulfil regulatory requirements.
12.1.5 Reporting of Adverse Events
AE reporting on each subject will start after the ICF has been signed. The reporting will continue 
during each follow-up visit (including telephone contacts and extra visits between planned visits) 
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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.
12.1.6 Follow-up of Unresolved Events after Study Termination and New Events after Study 
Termination
All serious as well as non-serious AEs with a causal relationship to the study product or treatment 
procedure with onset after subject participation in the study has ended shall be collected and 
reported to Sponsor on a paper AE form or in the post marketing AE form or SAE paper form if 
applicable. The events shall thereafter be followed up until resolved or considered chronic or 
stable, or for at least three months. Final outcome shall be reported on the AE follow up form. 
12.1.7 Pregnancy
Pregnancy itself is not regarded as an AE.
If there is a pregnancy during the study period the subject must continue to be followed within the 
study and the outcome of pregnancy must be reported even if the expected date of delivery occurs 
after study completion. 
A pregnancy confirmed during the study period must be reported by the Investigator on a 
pregnancy report form immediately upon acknowledge be submitted to the Sponsor according to 
contact details specified in section 1.3. The report can be prospective or retrospective. Follow-up 
shall be conducted to obtain outcome information on all prospective reports. 
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 
will not be reported as AEs.
12.1.8 Anticipated Adverse Events
After the injection some common injection-related reactions might occur with both products. 
These reactions include bruising, redness, itching, swelling, pain (including burn) or tenderness at 
the implant site. Typically these reactions start on the day of treatment and resolve spontaneous 
within a few days after injection into the skin, as observed in the Chinese clinical study for 
Restylane Vital and in consistent with international results for the product.
12.2 Device Deficiency
12.2.1 Definition of Device Deficiency
A device deficiency is defined as an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety* or performance.
Note: Device deficiencies include malfunctions, use errors, and inadequate labelling.
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*Inadequacy of device safety refers to properties of the device which could have or have led to an AE.
12.2.2 Recording Instructions
When a device deficiency is discovered the Clinical Study Complaint Form in the eCRF will 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 module or a SAE Form should be completed following instructions in section 
12.4. 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
The Sponsor will also make the same assessment in the Clinical Study Complaint Form.
12.2.3 Reporting Device Deficiency
The Investigator will complete the Clinical Study Complaint Form to the Sponsor using the 
contact details specified in section 1.3. A device deficiency that led to a SAE and any device 
deficiency that could have led to a SAE shall be reported within 24 hours after the Investigator’s 
awareness in accordance to section 12.4. 
In order to fulfil regulatory reporting requirements, all deficiencies with the study product must be 
assessed by both the Investigator and the Sponsor to determine if it could have led to a SAE. 
If an SAE has resulted from a device deficiency or if either the Investigator or the Sponsor 
assesses that the device deficiency could have led to an SAE the event will be reported in 
accordance with Regulatory requirements, as applicable.
The deficient study product shall be kept, if applicable, by the study site until the QA complaints 
group has confirmed whether the product shall be returned to Sponsor for further study or if it can 
be destroyed at the study site.
12.3 Definition of Serious Adverse Events
A SAE is an AE that:

led to death,

led to serious deterioration in the health of the subject, that either resulted in
1.
a life-threatening** illness or injury, or
2.
a permanent impairment of a body structure or body function, or
3.
in-patient or prolonged hospitalisation***, or
4.
medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 
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
led to foetal distress, foetal 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.
**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).
*** 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).
12.4 Reporting Process, Contact Person Information
After aware of any SAE, the Investigator shall report it to his/her administrative department of 
medical device clinical trials under the clinical trial institution, which in turn shall notify the 
Sponsor Representative in writing. This initial report can be made via fax or e-mail.
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:
CTN
Subject identification (age, gender, subject number)
AE description
date when AE occurred
date when AE became serious
Name of PI and original reporter (if other than Investigator) 
Name of study product
Treatment specification
The Investigator will assure completeness of the SAE information and the supporting 
documentation.
Follow-up information and data missing in the initial SAE reporting shall be gathered as soon as 
possible and reported to the Sponsor via Sponsor’s representative 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 by the Investigator.
Supporting documentation to be provided with the SAE report:

Concomitant Medication Form/list

Concomitant Procedure/Treatment Form/list
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
AE Form/list

Medical History Form/list

Any other relevant supporting documentation (e.g. hospital notes, death certificate, autopsy 
reports etc.)
_______________________________________________________________________
Fax number for SAE reporting: +46 (0)18 474 91 75 
E-mail for SAE reporting:      
safety.q-med@galderma.com
Surface mail for providing
              
complementary information:    
safety.q-med@galderma.com
_______________________________________________________________________
For non-urgent complementary information not possible to send by e-mail or fax, please use 
surface mail.
The SAE form must be signed and dated by the Investigator. If the initial 24-hour SAE report does 
not contain full information or if it is made without using the SAE form, the fully completed and 
signed SAE form shall be e-mailed or faxed to the Sponsor (contact details refer to 24-hour contact 
person list in the Investigator Site File [ISF]). A copy of the fully completed SAE form shall be 
kept at the site. 
In addition, according to national regulations, the investigator will report a SAE Form to the 
administrative department of medical device clinical trials in his/her hospital, and they should, 
within 24 hours, deliver a written report to the corresponding Ethics Committee. In case of a death 
incident, the clinical trial institutions and investigators should furnish the Ethics Committee and 
the Sponsor Representative with all required materials.
The Sponsor shall report to other medical device clinical trial institutions, ethics committees and  
principal investigators participating in the clinical trial, report to the drug regulatory authorities of 
the provinces, autonomous regions and municipalities directly under the central government where 
the Sponsor is located, report to the drug regulatory authority and health administrative authority 
of the province, autonomous region or municipality directly under the central government where 
the medical device clinical trial institution is located, and take risk control measures within 7 days 
after being informed of death or life-threatening serious adverse events related to the clinical trial 
medical device, and within 15 days after being informed of non-death or non-life-threatening 
serious adverse events related to the clinical trial medical device and other serious safety risk 
information. 
13 Requirements on Protocol Deviation and Protocol Amendments
The PI and other site personnel involved in the study must not implement any deviation from or 
changes to the CSP without agreement with the Sponsor and prior review and documented 
approval from the IEC, except where necessary to eliminate an immediate hazard to the subjects. 
All changes to the final CSP must be documented in a written protocol amendment. However, 
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administrative changes are to be documented in the Sponsor file without requiring a protocol 
amendment.
Subjects with CSP deviations will be listed individually, including subject number and observed 
deviation. Depending on the seriousness of the deviation, subject might be excluded from the PP 
population, which shall be documented prior to database lock.
Deviations from the statistical plan will be documented.
14 Access to Source Data and Source Documents
14.1 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 photographs, memoranda, material dispensing records, subject files, etc.
The PI 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 photographs, should be clearly identified with 
the subject number. Any personal information, including name, shall be removed or rendered 
illegible to preserve individual confidentiality.
14.2 Record Keeping and Access to Source Data
The PI/institution shall permit study-related monitoring, audits and IEC review 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 should be 
retained by the PI as required by local legislation and international guidelines. Any transfer of 
responsibility for storage of the records shall be documented and the Sponsor should 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 shall 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. 
The source data location log specifies what data that should be available in the medical record. The 
source data location log should also specify the data for which the eCRF serves as the source. Such 
data only need to be recorded in the eCRF and are typically associated with study-specific 
procedures and not with normal clinical care practice. For this type of study data the Investigator 
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would not be expected to duplicate the information into the medical record.
14.3 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 after study completion according to national legislation and the CTA. Sponsor 
will inform the sites as to when these documents no longer needs to be retained. Measures should 
be taken to prevent accidental or premature destruction of these documents (e.g. protection against 
damage and unauthorised access, preferably by storage in a fire-proof cabinet). Refer to the CTA.
After study completion and database lock, a security sealed CD with electronic study data shall be 
provided by the eCRF vendor for archiving.
It is the PI’s responsibility to inform Galderma SA in writing if the Investigator file is moved or if 
the responsibility for the documents is transferred to someone else.
15 The Contents of Clinical Study Report
The Clinical Study Report (CSR) for this clinical trial will be developed in accordance with the 
regulatory standards set by the National Medical Products Administration (NMPA). The report 
will provide an exhaustive and detailed account of the clinical trial's implementation, outcomes, 
and inferences. Overall, the CSR will encompass but not limited to the following elements:

Title Page

Synopsis

Basic Information on Clinical Trials

Implementation Status

Statistical Analysis Method

Trial Results

Adverse Events

Report on Device Defects and Their Handling

Discussion and Analysis of Trial Results

Conclusion of Clinical Trials

Ethical Situation Explanation
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
Existing Issues and Improvement Suggestions
16 Confidentiality
For the purposes of the study, Sponsor will be considered the data controller, and Institution and PI 
will both be considered data processors.
All processing of personal data must be carried out in accordance with national legislation 
concerning the protection of personal data. The Institution and the PI are responsible for 
complying with all requirements pursuant to national legislation in the country in which the 
Institution and the PI are located. The Sponsor will ensure that all requirements are complied with 
for data processing, which is carried out in Sweden by the Sponsor.
The Informed Consent Form shall contain information about what personal data to be collected in 
the study and that this will be kept confidential. The provided information shall be sufficient to 
enable all subjects to give their consent not only to the participation in the study, but also to the 
processing of personal data. Such information includes information regarding the purposes of the 
collecting, processing, data transfer to countries outside China, and the length of time during 
which personal data will be stored. The subject shall have the right of access to stored personal 
data, and the right to correction of incorrect information. If a subject decides to terminate the study 
prematurely, data collected before withdraw of consent will be used in the evaluation of the study, 
however no new data may be collected. Authorized representatives from the Sponsor or a RA may 
visit the study site to perform audits/inspections, including source data verification, i.e. comparing 
data in the subjects’ medical records and the eCRF. Data and information shall be handled strictly 
confidential.
17 Responsibilities of Each Party
A contractual agreement, the CTA, outlines the Site’s responsibilities, compensation and payment 
terms of the study and must be signed between the CRO/Sponsor and each investigator/institution 
before the first subject is screened in the study.  This document will contain supplementary 
information, including financial terms, confidentiality, the clinical study schedule, third party 
responsibility, and publication rights. If there are differences between the CTA and the CSP 
regarding certain rights and obligations, the CTA is the prevailing document.
18 Any Other Information to be Specified
18.1 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 
CSP regarding certain rights and obligations, the CTA is the prevailing document. Galderma SA’s 
obligations in this clinical study are covered by the Galderma group’s global general liability 
program. An insurance certificate will be provided upon request. The institution/PI is obligated to 
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maintain insurance coverage for their obligations in the clinical study according to the CTA.
18.2 Publication Policy
The PI’s, institutions, and Galderma SA’s obligations regarding intellectual property rights, 
confidentiality, and publications are described in detail in the CTA.
The aim is to submit the results of this study for publication in the public database 
ClinicalTrials.gov and to a medical journal for a first joint publication of the results. Everyone who 
is to be listed as an author of the results of this multicentre study shall have made a substantial, 
direct, intellectual contribution to the work. Authorship will be based on (1) substantial 
contributions to the conception or design of the work; or the acquisition, analysis, or interpretation 
of data for the work; and (2) drafting the work or revising it critically for important intellectual 
content; and (3) final approval of the version to be published; and (4) agreement to be accountable 
for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part 
of the work are appropriately investigated and resolved*. 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 should be 
acknowledged. Among the authors that fulfil the above mentioned criteria, one author will be 
appointed by Galderma SA to take primary responsibility for the overall work as primary author.
*Defining the role of authors and contributors, compiled by the International Committee of Medical Journal 
Editors (ICMJE) (http://www.icmje.org).
18.3 Suspension or Premature Termination
The Sponsor will suspend or terminate the study when so instructed by the IEC or if it is judged 
that the subjects are subjected to unreasonable risks, or for valid scientific or administrative 
reasons. 
The Sponsor may also decide to close a single study site due to unsatisfactory subject enrolment or 
non-compliance with the CSP, GCP, or applicable regulatory requirements.
In the event of premature termination, Galderma SA will provide information on the handling of 
currently enrolled subjects who have not completed the study.
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Statement of Principal Investigator
I acknowledge:
(1) Strictly follow Declaration of Helsinki, the current regulations in China and the 
requirements of study protocol to conduct this study
(2) Record all required study data into case report form (CRF) accurately, and 
contribute to clinical study report
(3) Study medical device is only used in this study. The shipment and use of study 
medical device in this study should be documented completely and accurately, 
and kept in a proper manner
(4) Allow the monitor and auditor authorized or assigned by Sponsor, and the 
regulatory authority to monitor, audit and inspect this study
(5) Strictly follow clinical study contract/agreed terms by all parties 
I have already read and understood the study protocol, including above mentioned 
statements, and I agree all contents above.
Principal Investigator
   Signature: 
  yyyy-mm-dd        
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Clinical Study Institution
  Stamp
yyyy-mm-dd        
Sponsor
   Stamp 
 yyyy-mm-dd        
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References list
1.
Monheit GD, Coleman KM. Hyaluronic acid fillers. Dermatol 2006 May.
2.
Gold M. The science and art of hyaluronic acid dermal filler use in esthetic applications. J 
Cosmet Dermatol 2009 Dec;8(4):301-7.
3.
43CH1504 Clinical Study Report, Internal Doc. No. MA-33230 ver 2.0.
4.
43TW1628 Clinical Study Report, Internal Doc. Np. MA-37493 ver 1.0.
5.
Caracas HC et al. The use of lidocaine as an anti-inflammatory substance: a systematic 
review. Dent. 2009 Feb;37(2):93-7.
6.
Dias MP et al. The inhibitory effects of local anaesthetics on the vascular flare responses to 
bradykinin and substance P in human skin. Anaesthesia 2008:63(2):151-5.
7.
43CH1406 Clinical Study Report, Internal Doc. No. MA-35796 ver 1.0.
8.
Galderma protocol QMS-7483. Instructions for use Restylane Vital Lidocaine.
9.
Clinical Study Report CTN 05DF1206 Acne scars. Dierickx C, Larsson MK, Blomster S. 
Effectiveness and Safety of Acne Scar Treatment With Nonanimal Stabilized Hyaluronic 
Acid Gel. Dermatol Surg. 2018 Nov;44 Suppl 1:S10-S18.
10.
Clinical Study Report 05DF1211. Hedén P, Hexsel D, Cartier H, Bergentz P, Delmar H, 
Camozzato F, Siega C, Skoglund C, Edwartz C, Norberg M, Kestemont P. Effective and 
Safe Repeated Full-Face Treatments With AbobotulinumtoxinA, Hyaluronic Acid Filler, 
and Skin Boosting Hyaluronic Acid. J Drugs Dermatol. 2019 Jul 1;18(7):682-689. .
11.
05DF1404 Clinical Study Report, Internal Doc. No. MA-36906. .
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Appendix 1 Visual Analogue Scale (VAS)
Please mark, with a vertical line, how much pain you feel at the different timepoints.
VAS pain assessment RIGHT hand:
0 minutes post-treatment
No pain
The worst pain 
you can imagine
 0
  10
10 minutes post-treatment
No pain
The worst pain 
you can imagine
 0
  10
20 minutes post-treatment
No pain
The worst pain 
you can imagine
 0
  10
30 minutes post-treatment
No pain
The worst pain 
you can imagine
 0
  10
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VAS pain assessment LEFT hand 
0 minutes post-treatment
No pain
The worst pain 
you can imagine
 0
  10
10 minutes post-treatment
No pain
The worst pain 
you can imagine
 0
  10
20 minutes post-treatment
No pain
The worst pain 
you can imagine
 0
  10
30 minutes post-treatment
No pain
The worst pain 
you can imagine
 0
  10
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SIGNATURES PAGE
Date
Signed by
2024-03-12 19:39
Justification
Approved by Technical Expert
2024-03-13 01:47
Justification
Approved by Trainer
2024-03-13 08:22
Justification
Approved by Technical Expert
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Justification
Approved by Owner
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