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

KYLANE  
LABORATOIRES SA 
FILLGEL 
CIP #22E0978 
Final version 2.0 
Date: 21/09/2022 
Confidential 
Page 12/74 
 
 
PRM03-F-227_V6_EN  
Clinical investigational plan for MD 
 
1.5 
OVERALL SYNOPSIS OF THE CLINICAL INVESTIGATION 
 
ANSM registration #: 
2022-A01183-40 
Clinical investigation plan #: 
22E0978 
Title of the clinical investigation: 
SAFETY AND EFFECTIVENESS CLINICAL EVALUATION OF 
THE RANGE OF INJECTABLE MEDICAL DEVICES FILLGEL IN 
FACIAL 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 FILLGEL 
range used on different treated zones one month (M1) after treatment 
using clinical evaluation of the global aesthetic improvement (GAIS) 
rated by the independent investigator. 
 
The secondary objectives of the study are to collect data for the 
FILLGEL range on: 
-     the effectiveness of the range used on different treated zones 
six months (M6) and twelve months (M12) after treatment 
using clinical evaluation of the global aesthetic improvement 
(GAIS) rated by the independent investigator . 
- 
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 M1, M6 and 
M12. 
- 
subject’s satisfaction and subject’s opinion on aesthetic 
improvement on the different treated zones using clinical 
evaluation of the GAIS at M1, M6 and M12. 
- 
the injector’s satisfaction on the injection quality using 
subjective evaluation questionnaire, 
Another objective will be to illustrate the device effectiveness by 
realization of face macrophotographs. 
Design: 
¨ Open study,  
¨ intra-individual, 
¨ single dose,  
¨ single centre. 
Planned Sample Size: 
68 subjects in total divided in 4 subgroups of 17 subjects, according 
to the kind of filler injected: 
Group 1: 17 subjects treated in peri-oral lines by FILLGEL 0 
Group 2: 17 subjects treated in nasolabial folds and/or in lips by 
FILLGEL 1 (with at least 10 in nasolabial folds and 7 in lips, both 
indications possible on the same subjects). 
Group 3: 17 subjects treated in cheek/cheekbones by FILLGEL 2. 
Group 4: 17 subjects treated in cheek/cheekbones and/or chin by 
FILLGEL 3 (with at least 10 in cheeks/cheekbones and 7 in chin, both 
indications possible on the same subjects). 
 
Number of investigational study 
sites: 
1 (Eurofins Dermscan Pharmascan) 

KYLANE  
LABORATOIRES SA 
FILLGEL 
CIP #22E0978 
Final version 2.0 
Date: 21/09/2022 
Confidential 
Page 13/74 
 
 
PRM03-F-227_V6_EN  
Clinical investigational plan for MD 
 
Inclusion criteria: 
1. Healthy Subject. 
2. Sex: male or female. 
3. Age: between 18 and 65 years. 
4. Subject seeking an improvement of her/his face aspect with HA 
filler.  
*For group 1: Subject with moderate to severe peri-oral lines 
(score 3 to 5 on Bazin Upper lip scale) ; 
*For group 2: Subject with moderate to severe nasolabial folds 
(score 3 to 4 on WSRS scale) and/or subject with thin lips (score 
1 or 2 for superior and/or inferior lip on the Rossi scale) and 
seeking an improvement of lip volume; 
      *For 
group 
3: 
Subject 
with 
moderate 
to 
severe 
cheeks/cheekbones volume deficit (score 3 to 4 on Ascher 
lipoatrophy scale); 
      *For 
group 
4: 
Subject 
with 
moderate 
to 
severe 
cheeks/cheekbones volume deficit (score 3 to 4 on Ascher 
lipoatrophy scale) and/or subject seeking improvement of chin 
enhancement. 
5. Subject whose weight did not fluctuate in the last 6 months and 
who agrees to keep a stable weight during the study. 
6. Subject having given their free, express, and informed consent. 
7. Subject psychologically able to understand the information 
related to the study, and to give their written informed consent. 
8. Subject registered with a social security scheme. 
9. Women of childbearing potential should use a contraceptive 
method considered effective since at least 4 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 4.500 euros as 
compensations for their participation in research involving 
human beings 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 
FILLGEL 
CIP #22E0978 
Final version 2.0 
Date: 21/09/2022 
Confidential 
Page 14/74 
 
 
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 hypersensitivity to one of the 
ingredients of the investigational device (i.e. HA), to 
antiseptic 
solution 
(Diaseptyl®) 
or 
to 
amide-type 
anaesthetics (EMLA®), related to previous or current 
treatments. 
15. Subject 
with 
previous 
hypersensitivity 
reactions 
to 
hyaluronic acid injections after a COVID-19 vaccination. 
Relating to previous or ongoing treatment 
16. Any medication which may interfere, at the interpretation of 
the investigator, with the study objectives.  
17. 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 face within the past 6 months or who 
plans to undergo any of these procedures during the study.  
18. 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), autologous fat, 
mesotherapy or botulinum neurotoxin on or near the treated 
zone.   
19. Subject having received at any time or planning to receive a 
permanent filler on the face (e.g., polylactic acid, 
Polymethylmethacrylate, silicone) during the study. 
20. Subject with subcutaneous retaining structure on the face 
(meshing, threads, gold strand). 
21. 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. 
22. 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 
23. Intensive exposure to sunlight or UV-rays within the previous 
month and/or planning to do so during the study. 
24. Subject planning to change her/his life habits during the 
study. 
25. 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 
Indication 
 
FILLGEL range: Injectable sterile gels in syringe 
1. FILLGEL 0: Indication:  Peri-oral lines 
2. FILLGEL 1: Indication: Nasolabial folds / lip volume 
3. FILLGEL 2: Indication: Cheeks, cheekbones 

KYLANE  
LABORATOIRES SA 
FILLGEL 
CIP #22E0978 
Final version 2.0 
Date: 21/09/2022 
Confidential 
Page 15/74 
 
 
PRM03-F-227_V6_EN  
Clinical investigational plan for MD 
 
4. FILLGEL 3: Indication: Cheeks, cheekbones / chin 
Endpoints: 
Primary endpoint: 
Proportion of subjects having an improvement of the zone treated 
with the overall FILLGEL range of devices as assessed by the 
independent investigator, one month 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: 
- The safety of the FILGEL range and of each FILLGEL 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 and early ISRs by the independent 
investigator immediately and one (M1), six (M6) and twelve 
months (M12) after treatment.  
• collection of AEs throughout the study. 
 
- Proportion of subjects having an improvement of the zone treated 
with the overall FILLGEL range of devices as assessed by the 
independent investigator, six and twelve months after treatment, 
using the GAIS.   
 
- Proportion of subjects having an improvement of the zone treated 
with each FILLGEL device for the four indications independently as 
assessed by the independent investigator, one, six and twelve 
months after treatment, using the GAIS.   
 
- Proportion of subjects having an improvement of the zone treated 
with the FILLGEL range of devices overall as assessed by the 
subjects, one, six and twelve months after treatment, using the GAIS.  
 
- Proportion of subjects having an improvement of the zone treated 
with each FILLGEL device for the four indications independently as 
assessed by the subjects, one, six, and twelve months after 
treatment, using the GAIS. 
 
- Evaluation of the effectiveness on wrinkles/lines filling of the device 
FILLGEL 0 used in the peri-oral lines as assessed by the 
independent investigator one, six and twelve months after treatment, 
using the Bazin Upper lip wrinkles scale.   
 
- Evaluation of the effectiveness on folds filling of the device FILLGEL 
1 used in the nasolabial folds as assessed by the independent 
investigator one, six and twelve months after treatment, using the 
WSRS scale.   
 
- Evaluation of the effectiveness on lip volume increase of the device 
FILLGEL 1 used in lips as assessed by the independent investigator 
one, six and twelve months after treatment, using the Rossi scale.   
 
- Evaluation of the effectiveness on volume restauration of the device 
FILLGEL 2 used in the cheeks/cheekbones as assessed by the 
independent investigator, one, six and twelve months after treatment, 
using the Ascher lipoatrophy scale. 
 

KYLANE  
LABORATOIRES SA 
FILLGEL 
CIP #22E0978 
Final version 2.0 
Date: 21/09/2022 
Confidential 
Page 16/74 
 
 
PRM03-F-227_V6_EN  
Clinical investigational plan for MD 
 
- Evaluation of the effectiveness on volume restauration of the device 
FILLGEL 3 used in the cheeks/cheekbones as assessed by the 
independent investigator, one, six and twelve months after treatment, 
using the Ascher lipoatrophy scale.   
   
- Injector’s satisfaction on the injection quality using a questionnaire 
completed immediately after injection on D0.  
 
- Illustration of the treatment effect one, six and twelve months after 
treatment compared to baseline by photographs taking. 
Study Procedures: 
Screening, D0, D7 (phone call for safety), M1, M6, M12 
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. 
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:  
For the parameter GAIS investigator with the 5 level scores (at D0 
after injection, M1, M6 and M12), the frequencies and percentages 
will be presented for the overall face score and for the scores by 
product. 
Two derived parameters will be defined based on the parameters 
GAIS subject and investigator as a scores 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 
Confidence Interval (CI) 95%. 
Inferential analysis for the primary evaluation criteria 
For the new derived parameters at M1 (1 month after injection) for 
the GAIS Investigator, a binomial exact test (bilateral approach) vs 
50% will be applied at each time point for the overall face score. 
This test will compare the proportion of improvement to 50%. 
 
For the secondary evaluation criteria: 
 
All the variables will be described using adapted statistics according 
to their type (quantitative data or qualitative data). 
Statistical tests will be performed, to assess the change from 
baseline (Wilcoxon signed rank test). 
 
The bilateral approach will be used with a significance level of 0.05. 

KYLANE  
LABORATOIRES SA 
FILLGEL 
CIP #22E0978 
Final version 2.0 
Date: 21/09/2022 
Confidential 
Page 17/74 
 
 
PRM03-F-227_V6_EN  
Clinical investigational plan for MD 
 
Estimated dates of the study: 
Clinical investigation beginning: Q4 2022  
Clinical investigation end: Q4 2023/Q1 2024 
Expected recruitment period duration: 3 months 
Clinical investigation overall duration: 12 months + recruitment period 
Duration by subject: 12 months + screening period  
 
 
 

KYLANE  
LABORATOIRES SA 
FILLGEL 
CIP #22E0978 
Final version 2.0 
Date: 21/09/2022 
Confidential 
Page 18/74 
 
 
PRM03-F-227_V6_EN  
Clinical investigational plan for MD 
 
FLOW-CHART 
Procedure 
Visit 1 
Screening 
Visit 2 
Day 0  
Phone call 
Day 7 
Visit 3 
M1 
Visit 4 
M6 
Visit 5 
M12 
Days 
D-x 
D0 
D7 ± 1 
D30±7 
D180±14 
D365±14 
Informed 
consent 
form 
signature 
● 
 
 
 
 
 
Medical examination 
● 
 
 
 
 
 
Medical 
history 
and 
previous and concomitant 
treatments collection 
● 
 
 
 
 
 
Verification 
of 
the 
inclusion and exclusion 
criteria 
● 
 
 
 
 
 
Urinary pregnancy test (for 
women with childbearing 
potential) 
 
●b 
 
 
 
 
Confirmation of eligibility 
 
●b 
 
 
 
 
Photographs (full face + 2 
profiles) 
 
●b 
 
● 
● 
● 
Scoring of effectiveness 
using specific scales 
 
●b 
 
● 
● 
● 
Injection  
 
● 
 
 
 
 
Injector 
satisfaction 
questionnaire 
 
●a 
 
 
 
 
GAIS live assessment by 
the 
independent 
investigator 
 
●a 
 
● 
● 
● 
GAIS assessment by the 
subjects 
 
 
 
● 
● 
● 
Distribution of a subject 
daily-log 
● 
● 
 
● 
● 
● 
ISR collection by subject 
 
● 
Each day during one month after injection, on 
the daily-log 
 
 
ISR investigator 
 
●a 
 
● 
● 
● 
AE 
and 
concomitant 
treatments 
and 
procedures collection 
● 
● 
● 
● 
● 
● 
a : after injection, b : before injection 
AE: Adverse Event - GAIS: Global Aesthetic Improvement Scale- ISR: Injection Site Reaction