Safety and Effectiveness Clinical Evaluation of Range of Injectable Medical Devices Viscol in Aesthetic Treatment
Phase: NA
Conditions: Aesthetic Dermatology
Sponsor: Kylane Laboratoires

KYLANE  
LABORATOIRES SA 
VISCOL 
CIP #23E1077 
Final version 2.0 
Date: 26/10/2023 
Confidential 
Page 13/77 
 
 
PRM03-F-227_V6_EN  
Clinical investigational plan for MD 
 
1.5 
OVERALL SYNOPSIS OF THE CLINICAL INVESTIGATION 
 
ANSM registration #: 
2023-A01479-36 
Clinical investigation plan #: 
23E1077 
Title of the clinical investigation: 
SAFETY AND EFFECTIVENESS CLINICAL EVALUATION OF 
THE RANGE OF INJECTABLE MEDICAL DEVICES VISCOL IN 
AESTHETIC TREATMENT 
Sponsor: 
KYLANE LABORATOIRES SA 
Chemin du Pré-Fleuri 1-3 
CH-1228 Plan-les-Ouates 
SWITZERLAND 
Development phase 
Exploratory study  
Objectives: 
The primary objective is to evaluate the effectiveness of the VISCOL 
range used on different treated zones (facial and body areas) one 
month (M1) after treatment using clinical evaluation of the global 
aesthetic improvement (GAIS) rated by an independent investigator. 
 
The secondary objectives of the study are to collect data for the 
VISCOL range on: 
- 
the effectiveness of the range used on different treated zones 
four months (M4) after treatment using clinical evaluation of 
the global aesthetic improvement (GAIS) rated by an 
independent investigator. 
- 
the effectiveness on the improvement of facial skin quality by 
objective measurements of skin biomechanical parameters  
using Cutometer® and skin hydration using Moisturemeter® 
one (M1) and four (M4) months after treatment. 
- 
subject’s satisfaction and subject’s opinion on aesthetic 
improvement on the different treated zones using clinical 
evaluation of the GAIS at M1 and M4. 
- 
the injector’s satisfaction on the injection quality using 
subjective evaluation questionnaire after injection on D0. 
- 
the safety using clinical evaluation of the Injection Site 
Reactions (ISR) rated by the subject and the investigator, 
and by collection of adverse events (AEs) at Day 0 (D0) one 
month (M1),four months (M4) and six months (M6). 
Another objective will be to illustrate the device effectiveness by 
realization of face and body macrophotographs. 
Design: 
 Open study,  
 intra-individual, 
 single dose,  
 single centre. 
Planned Sample Size: 
86 subjects in total divided in 2 groups, according to the kind of 
treated zone: 
Group 1 (VISCOL Face): 64 subjects treated by VISCOL (one 
injection on D0) on both sides of the face in the following areas: malar 
and sub-malar areas (obligatory areas) and optional areas 
mandibular and/or chin. 
Group 2 (VISCOL Body): 22 subjects treated by VISCOL (one 
injection on D0) on both sides in the following areas: decolletage and 
neck areas (obligatory areas) and one optional area abdomen or 
internal face of the arm. 

KYLANE  
LABORATOIRES SA 
VISCOL 
CIP #23E1077 
Final version 2.0 
Date: 26/10/2023 
Confidential 
Page 14/77 
 
 
PRM03-F-227_V6_EN  
Clinical investigational plan for MD 
 
Number of investigational study 
sites: 
1 (Eurofins Dermscan Pharmascan in France)  
Inclusion criteria: 
1. Healthy Subject. 
2. Sex: male or female. 
3. Age: between 35 and 70 years. 
4. Subject seeking an improvement of her/his face (at least malar 
and sub-malar areas and optionally mandibular and/or chin 
areas) or body (at least decolletage/neck areas and optionally 
abdomen or internal face of the arm areas) aspect with HA skin 
quality improvement product. 
5. For Group 1 (Face): Subjects with dry skin (skin hydration rate 
on cheekbones < 60UA confirmed using Corneometer® 
measurement).  
6. For Group 2 (Body): If applicable: subject with mild to moderate 
laxity of the tissues of the internal face of the arms (from 1 to 3 
on Bazin Texture of the arm scale) or the abdomen (from 2 to 5 
on Bazin Abdomen texture scale) 
7. For Group 2 (Body): Subject with BMI <30.  
8. Subject whose weight did not fluctuate in the last 6 months and 
who agrees to keep a stable weight during the study. 
9. Subject having given his/her free, express, and informed 
consent. 
10. Subject psychologically able to understand the information 
related to the study, and to give their written informed consent. 
11. Subject registered with a social security scheme. 
12. Women of childbearing potential should use a contraceptive 
method considered effective since at least 12 weeks and 
throughout the study. 
Exclusion criteria: 
In terms of population 
1. Pregnant or nursing woman or planning a pregnancy during the 
study. 
2. Subject who had been deprived of their freedom by 
administrative or legal decision or who is under guardianship. 
3. Subject in a social or sanitary establishment. 
4. Subject suspected to be non-compliant according to the 
investigator’s judgment. 
5. Subject having received a total of 6.000 euros as compensations 
for their participation in clinical research in the last 12 months, 
including their participation in the present study. 
6. Subject enrolled in another study or whose non-enrollment 
period is not over. 
7. Subject with scar(s), mole(s), hair or any other lesion on the 
studied zones which might interfere with the evaluation (tattoo, 
permanent make-up…). 
 
In terms of associated pathology 
8. Subject suffering from a severe or progressive disease or any 
other pathology that may interfere with the evaluation of the 
study results and/or subject safety. 
9. Subject with known history of or suffering from autoimmune 
disease and/or immune deficiency. 
10. Subject suffering from active disease such as inflammation, 
infection, tumours, inflammatory and/or infectious cutaneous 
disorders (herpes, acne, rosacea, porphyria …) in the 6 months 
before screening visit.  
11. Subject with a history of streptococcal disease or an active 
streptococcus infection. 
12. Subject prone to develop inflammatory skin conditions or having 
tendency to bleeding disorders. 

KYLANE  
LABORATOIRES SA 
VISCOL 
CIP #23E1077 
Final version 2.0 
Date: 26/10/2023 
Confidential 
Page 15/77 
 
 
PRM03-F-227_V6_EN  
Clinical investigational plan for MD 
 
13. Subject predisposed to keloids or hypertrophic scarring or 
having healing disorders. 
14. Subject having history of severe allergy or anaphylactic shock 
including known risk of hypersensitivity to one of the components 
of the composition of the investigational device , to antiseptic 
solution (Diaseptyl®) or to amide-type anaesthetics (EMLA®), 
related to previous or current treatments. 
15. Subject with symptoms consistent with COVID-19 or are 
suffering from previous COVID-19 infection. 
16. Subject with previous hypersensitivity reactions to hyaluronic 
acid injections after a COVID-19 vaccination. 
Related to previous or ongoing treatment 
17. Subject having received a dose of COVID-19 vaccine within the 
3 weeks prior to injection visit or planning to receive a dose in 
the 2 weeks following injection. 
18. Any medication which may interfere, at the interpretation of the 
investigator, with the study objectives.  
19. Subject having received treatment with a laser, ultrasound or 
radiofrequency treatment, a dermabrasion, a surgery, a 
chemical peeling or any other procedure based on active dermal 
response on the treated areas within the past 6 months or who 
plans to undergo any of these procedures during the study.  
20. Subject having received within the past 18 months or planning 
to receive during the study any injections outside of those in the 
study protocol including non-permanent fillers (e.g., HA, Calcium 
Hydroxyapatite) or autologous fat on or near the treated areas.   
21. Subject having received within the past 9 months or planning to 
receive during the study any injections outside of those in the 
study protocol including mesotherapy or botulinum neurotoxin 
on or near the treated areas. 
22. Subject having received at any time or planning to receive a 
permanent filler on treated areas (e.g., polylactic acid, 
Polymethylmethacrylate, silicone) during the study. 
23. Subject with subcutaneous retaining structure on treated areas 
(meshing, threads, gold strand). 
24. Subject using medication such as aspirin, nonsteroidal anti-
inflammatory drugs (NSAIDs), antiplatelet agents, thrombolytics 
or anticoagulants within one week prior to injection visit or being 
a chronic user. 
25. Subject undergoing a topical treatment on the test area or a 
systemic treatment: 
- 
anti-inflammatory medication and/or antihistamines 
within the past 2 weeks and during the study, 
- 
corticosteroids within the past 2 weeks and during 
the study, 
- 
retinoids and/or immunosuppressors within the past 
3 months and during the study. 
 
In terms of lifestyle 
26. Intensive exposure to sunlight or UV-rays within the previous 
month and/or planning to do so during the study. 
27. Subject planning to change her/his life habits during the study. 
28. Subject with an excessive consumption of alcohol (more than 2 
glasses of wine per day) and/or tobacco (more than 10 cigarettes 
per day).  
Investigational device: 
Name / code 
Galenic form 
VISCOL range: Injectable sterile gels in syringe 

KYLANE  
LABORATOIRES SA 
VISCOL 
CIP #23E1077 
Final version 2.0 
Date: 26/10/2023 
Confidential 
Page 16/77 
 
 
PRM03-F-227_V6_EN  
Clinical investigational plan for MD 
 
Indication 
 
1. VISCOL Face: Indication:  malar, sub-malar, mandibular and chin 
areas 
2. VISCOL Body: Indication: decolletage, neck, abdomen and 
internal face of the arms areas 
Endpoints: 
Primary endpoint: 
Proportion of subjects having an improvement of the zone treated 
with the overall VISCOL range of devices as assessed by an 
independent investigator, one month (M1) after treatment, using the 
GAIS.   
An improvement is defined as a subject with “very much improved”, 
“much improved” or “improved” score on the GAIS. 
 
Secondary endpoints: 
- Proportion of subjects having an improvement of the zone treated 
with the overall VISCOL range of devices as assessed by an 
independent investigator four months (M4) after treatment, using the 
GAIS.   
- Proportion of subjects having an improvement of the zone treated 
with each VISCOL device for the 2 groups independently as 
assessed by the independent investigator one month (M1) and four 
months (M4) after treatment, using the GAIS.   
- Proportion of subjects having an improvement of the zone treated 
with the VISCOL range of devices overall as assessed by the 
subjects, one month (M1) and four months (M4) after treatment, 
using the GAIS.   
- Proportion of subjects having an improvement of the zone treated 
with each VISCOL device for the 2 groups independently as 
assessed by the subjects, one month (M1) and four months (M4) 
after treatment, using the GAIS. 
- Change from baseline of facial skin hydration measured with 
Moisturmeter® one month (M1) and four months (M4) after treatment. 
- Change from baseline of facial skin biomechanical parameters 
measured with Cutometer® one month (M1) and four months (M4) 
after treatment.  
- Patient’s satisfaction on the treatment outcomes using a subjective 
evaluation questionnaire completed at one month (M1) and four 
months (M4) after treatment. 
- Injector’s satisfaction on the injection quality using a subjective 
evaluation questionnaire completed immediately after injection on 
D0.  
- The safety of the VISCOL range and of each VISCOL device 
independently will be assessed by:  
• collection of immediate and early Injection Site Reactions 
(ISRs) by the subjects on a daily-log every day up to one 
month after treatment.  
• collection of immediate Injection Site Reactions (ISRs) by 
the injector immediately after treatment. 
• collection of ISRs by the independent investigator one 
month (M1) and four months (M4) after treatment.  
• collection of AEs throughout the study. 
   
 Illustration of the treatment effect one month (M1) and four months 
(M4)  after treatment compared to baseline by photographs taking. 

KYLANE  
LABORATOIRES SA 
VISCOL 
CIP #23E1077 
Final version 2.0 
Date: 26/10/2023 
Confidential 
Page 17/77 
 
 
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Clinical investigational plan for MD 
 
Study Procedures: 
Screening, D0, D7 (phone call for safety), M1, M4, M6 (phone call for 
safety) 
Statistical methods: 
The statistical analysis will be performed by the CRO biostatistician. 
 
The analysis of the primary performance parameter will be performed 
on the ITT and PP population as sensitivity analysis. The conclusion 
of the primary performance parameter will be performed on the ITT 
population. 
The analysis of the secondary effectiveness parameters will be 
performed on the ITT and PP population. In case the ITT and PP 
population differ by less than 10%, only the PP population will be 
analyzed.  
 
The analysis of the safety/tolerance parameters will be performed on 
the “safety” population. 
 
A descriptive analysis of the population will be performed, including 
subject’s characteristics, subject’s disposition, deviations to the 
protocol, injections characteristics.  
 
For the primary evaluation criteria:  
 
Descriptive statistics: 
 
For the parameter GAIS investigator with the 5 level scores (at M1 
and M4), the frequencies and percentages will be presented for the 
overall face and body score and for the scores by product 
(separated by the 4 zones: “face”, “decolletage and neck”, “area 
abdomen” and “arm”). 
A two derived parameter will be defined based on the parameters 
GAIS subject and investigator as a score of 2 levels (1=Improvement 
(Very much improved, Much improved and Improved) and 2=No 
change or worsening). At each time point, these parameters will be 
described in frequencies, percentages and IC95% for the overall 
face and body score and for the scores by product (separated by 
the 4 zones: “face”, “decolletage and neck”, “area abdomen” and 
“arm”). 
• 
For group 1 :  
if GAIS value on face is “Very much 
improved”, “Much improved” or “Improved” then the subject is 
responder (Responder=‘Yes’) 
Else 
the 
subject 
is 
not 
responder 
(Responder=’No’) 
• 
For group 2 : if GAIS value on “decolletage and neck” is "Very 
much improved”, “Much improved” or “Improved” then the subject 
is responder (Responder=’Yes’) 
Else 
the 
subject 
is 
not 
responder 
(Responder=’No’) 
 
 
Inferential analysis for the primary evaluation criterion 
 
For the derived outcome responder rate at M1 (1 month after 
injection) for the GAIS Investigator, a binomial exact test (bilateral 
approach) vs 60% will be applied for the overall score. This test will 
compare the proportion of improvement to 60%. 

KYLANE  
LABORATOIRES SA 
VISCOL 
CIP #23E1077 
Final version 2.0 
Date: 26/10/2023 
Confidential 
Page 18/77 
 
 
PRM03-F-227_V6_EN  
Clinical investigational plan for MD 
 
 
In addition, a sensitivity analysis will be performed on a global binary 
variable based on both GAIS scores, assessed by the investigator 
and by the subject. If the subject is considered as improved by both 
scores, then the outcome will be “Improved” else the outcome will be 
“Not improved”. This composite parameter will be summarized in 
frequency and percentage and presented associated with its 95% CI, 
by time-point for the overall face and body scores and by product 
(separated by the 4 zones: “face”, “decolletage and neck”, “area 
abdomen” and “arm”). 
 
For the secondary evaluation criteria: 
 
GAIS subject : 
For the parameter GAIS subject with the 5 level scores (at M1 and 
M4), the frequencies and percentages will be presented for the 
overall face and body scores and for the scores by product 
(separated by the 4 zones: “face”, “decolletage and neck”, “area 
abdomen” and “arm”).  
 
 
Biometrological parameters: 
All the parameters measured with Cutometer® and Moisturemeter® 
will be summarized using the descriptive statistics for quantitative 
data for each time point (D0, M1, M4). 
 
For each parameter, a two-tailed paired t-test will be carried out to 
assess whether each time point after injection (M1, M4) differ 
significantly from the baseline value (D0).  
 
Subjective questionnaire statistical analysis: 
The distribution of each item of the injector and subject 
questionnaires will be described in frequencies and percentages.  
For each item of the subject questionnaire, the percentage of 
subject satisfied, (percentages of answers “totally agree”, “agree”) 
will be computed and described in frequencies and percentages.  
For each item of the injector questionnaire, the percentage of 
answers “satisfied” or “very satisfied” will be computed and 
described in frequencies and percentages. 
 
 Safety analysis: 
 
- 
The injection site reactions parameters assessed by the 
investigator and the subject will be described. 
- 
The individual listing of AE will be provided. 
AE/ADE will be summarized by product. AE/ADE will be further 
tabulated by seriousness, severity and relationship to the 
investigational device and procedure. 
 
Estimated dates of the study: 
Clinical investigation beginning: Q4 2023  
Clinical investigation end: Q3 2024 
Expected recruitment period duration: 4 months. 
Clinical investigation overall duration: 6 months + recruitment period 
Duration by subject: 6 months + screening period  
 
 
 

KYLANE  
LABORATOIRES SA 
VISCOL 
CIP #23E1077 
Final version 2.0 
Date: 26/10/2023 
Confidential 
Page 19/77 
 
 
PRM03-F-227_V6_EN  
Clinical investigational plan for MD 
 
FLOW-CHART 
Procedure 
Visit 1 
Screening 
Visit 2 
Day 0  
Phone call 
1 
Day 7 
Visit 3 
M1 
Visit 4 
M4 
Phone call 
2 
M6 
Days 
D-x 
D0 
D7 ± 1 
D30±4 
D120±7 
D180±7 
Informed consent  
● 
 
 
 
 
 
Medical examination to check 
inclusion and exclusion criteria  
● 
 
 
 
 
 
Medical history and previous/ 
ongoing treatment(s)  
● 
 
 
 
 
 
Confirmation of eligibility  
● 
● 
 
 
 
 
Urinary pregnancy test for women 
of childbearing potential 
 
●b 
 
 
 
 
Injection by injector  
 
● 
 
 
 
 
ISR by the injector 
 
●a 
 
 
 
 
Subjective evaluation 
questionnaire by the injector  
 
●a 
 
 
 
 
Subjective evaluation 
questionnaire by the patient  
 
 
 
● 
● 
 
GAIS by an independent 
investigator  
 
 
 
● 
● 
 
GAIS by the subjects 
 
 
 
● 
● 
 
ISR by an independent 
investigator 
 
 
 
● 
● 
 
ISR by the subjects 
 
● 
Each day during 1 month after injection, on the daily-
log 
 
 
Group 1: 
Macrophotographs (full face + 2 
profiles)  
 
●b 
 
● 
● 
 
Group 1:  
Cutometer® + Moisturemeter®  
 
●b 
 
● 
● 
 
Group 2: 
Macrophotographs of the treated 
zone(s)  
 
●b 
 
● 
● 
 
Adherence control, record of AE, 
concomitant treatments  
● 
● 
● 
● 
● 
● 
End of study form 
 
 
 
 
 
● 
a : after injection, b : before injection 
AE: Adverse Event – GAIS: Global Aesthetic Improvement Scale- ISR: Injection Site Reaction