Safety and Effectiveness of STYLAGE® L for Correction of Moderate and Severe Nasolabial Folds in Chinese Adults

Study Overview
=================
Brief Summary
-----------------
This is a safety and efficacy study of STYLAGE® Lin Chinese adults with Nasolabial Folds.

Detailed Description
-----------------
This is a prospective, multi-center, parallel-group, subject and evaluator-blinded, randomized controlled trial to demonstrate the non-inferiority of the study device, STYLAGE® L, when compared to an active comparator for the correction of moderate and severe NLFs. Subjects will randomly receive STYLAGE® L or the active comparator (ratio 1:1) injection in the NLFs at first visit on Day 0. Proportion of subjects having a NLFs severity improvement (blinded evaluation), 6 months after treatment initiation will be assessed and compared between the two groups. This will also be done during the other visits (1, 3, 9 and 12 months after treatment initiation). Global aesthetic improvement according to blinded independent evaluator and subject, subjects' satisfaction, and safety parameters will also be assessed during the study period.

Official Title
-----------------
A Controlled, Prospective, Randomized, Multi-Center, Subject and Evaluator-Blinded Study of the Safety and Effectiveness of STYLAGE® L Versus Restylane® for Correction of Moderate and Severe Nasolabial Folds in Chinese Adults

Conditions
-----------------
Aging, Skin Wrinkling

Intervention / Treatment
-----------------
* Device: STYLAGE® L
* Device: Active Comparator


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women aged ≥ 18 years. Chinese ethnicity. Subjects who wanting to correct his/her nasolabial folds Subjects with moderate to severe nasolabial folds (attaining grade 3 on both side or 4 on both side) in the WSRS of nasolabial fold, per assessment of the Blinded Evaluator. Subjects willing to abstain from other facial plastic surgical or cosmetic procedures during the study period. Subjects with realistic expectations who can understand and comply with the instructions and all visit schedule. Women of childbearing potential (WOCBP) who agree contraception during the study period. Subjects who voluntarily decided the participation of the study and signed the informed consent. Being able to stand mild pain. Exclusion Criteria: Subjects who are contraindicated to augmentation with HA fillers Subjects who had a history of keloid formation or hypertrophic scar Subjects presenting a scar or skin disorder (i.e. active dermal disease [facial psoriasis, eczema, rosacea, perioral dermatitis, acne, herpes, etc], inflammation or an unhealed wound) below the level of the lower orbital rim that may confound the study evaluation Has ever received semi-permanent fillers or permanent facial implants (eg, calcium hydroxyapatite, poly-L-lactic acid, polymethylmethacrylate, silicone, expanded polytetrafluoroethylene) anywhere below the inferior orbital rim, or is planning to be implanted with any of these products at any time during the study Has undergone temporary dermal filler treatment (e.g., hyaluronic acid or collagen) below the inferior orbital rim within 12 months before enrollment or is planning to undergo such treatment during the study Has undergone facial tissue augmentation with fat injections, botulinum toxin injections, mesotherapy, or cosmetic facial procedures (eg, facial liposuction, aesthetic surgery, face-lift, photomodulation, intense pulsed light, radio frequency, dermabrasion, laser or chemical peel, or other ablative procedures) below the inferior orbital rim within 6 months before enrollment or is planning to undergo any such treatment during the study Subjects who has any history of severe multiple allergies or an allergy resulting in anaphylaxis, or an allergy to hyaluronic acid and/or one of the ingredients of the study products Subject is pregnant or planning to be pregnant during the study period or lactating. Women of childbearing potential who have a positive pregnancy test result during screening. Women of childbearing potential who are unwilling to use effective birth control measures during the full course of the study Subject suffering from a serious or progressive disease, which, in the Investigator's judgment, put the subject at undue risk for participation in this clinical trial (i.e. cancer or pre-cancer, immunocompromised, uncontrolled diabetes, epilepsy, severe cardio-cerebrovascular disease(s) (i.e. stroke, idiopathic aortic stenosis, aneurysm, hypertrophic obstructive cardiomyopathy, ischaemic heart disease, tachyarrhythmias, severe heart failure [classified as NYHA III-IV], etc), , etc.) Subject having a history of cancer within 5 years Subjects who received oral surgery (eg. tooth extraction, orthodontia or implantation) within 6 weeks before enrollment or is planning to undergo any of these procedures during the study Subject has history or active autoimmune disease (e.g. inflammatory bowel disease), active or history of connective tissue disease (rheumatoid arthritis, scleroderma, and systemic lupus erythematosus) Subjects with current or a history of hemorrhagic diseases Subject who received chemotherapy, immunosuppressive agents, immunomodulatory therapy (e.g. monoclonal antibodies), systemic corticosteroids within 3 months (inhaled corticoids are allowed). Subjects unlikely to achieve a meaningful aesthetic result with the prescribed dosage regimen of the study product per Investigator's judgement Subjects who participated in other clinical trial within 30 days or who is in an exclusion period of one. Subjects with uncontrolled hypertension (systolic blood pressure above 160mmHg or diastolic blood pressure above 100 mmHg at resting status), and/or significant liver (serum ALT or AST ≥2X the upper limit of the reference range), kidney (BUN, Urea or Cr≥1.5X the upper limit of the reference range), and/or blood coagulation (PT, or APTT, or INR> 20% of the reference range) disorders per judgement of the Investigator. Current or a history of alcoholism, drug abuse, or drug dependence. Subject who had been deprived of their freedom by administrative or legal decision or who is under guardianship Subject with a past history of streptococcal disease (manifested by recurrent sore throat or acute rheumatic fever) or with an active infection to streptococcus Has facial hair (e.g., beards, sideburns, etc.), piercing or tattoo in the area to be treated that would interfere with investigation assessments and create inconsistency in required investigation photography during the study period Personnel of the study department, close relatives of the study department personnel (i.e. parents, children, siblings, or spouse), employees, or close relatives of employees at the Sponsor or CRO company. Other conditions the Investigator considers inappropriate for enrollment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Controlled, Prospective, Randomized, Multi-Center, Subject and Evaluator-Blinded Study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group Stylage L ®<br>Each subject will receive STYLAGE® L in both NLFs. STYLAGE® L will be injected in the NLFs by the Treating Investigator with optional touch-up injections on Month 1. | Device: STYLAGE® L<br>* Injection in both NLFs<br>|
| Active Comparator: Control group Active Comparator<br>Each subject will receive the Active Comparator in both NLFs. Active Comparator will be injected in the NLFs by the Treating Investigator with optional touch-up injections on Month 1. | Device: Active Comparator<br>* Injection in both NLFs<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WSRS improvement | Percentage of responders, defined by at least 1-point improvement from baseline 5-point WSRS, as measured by the Blinded Evaluator at 6 months after last treatment for both groups. | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WSRS improvement | Percentage of responders, defined by at least 1-point improvement from baseline 5-point WSRS, as measured by the Blinded Evaluator | 1, 3, 9, and 12 months | 
| GAIS assessment | Percentage of responders, defined by having Improved, Much improved or Very much improved according to the Global Aesthetic Improvement Scale (GAIS), as assessed by the subject and the Treating Investigator | 1, 3, 9, and 12 months | 
| Subject satisfaction assessment | Percentage of satisfied subjects on each question of the subject satisfaction assessment | 1, 3, 6, 9, and 12 month | 
| Device performance | Results of device performance evaluation after the initial and touch-up injection, respectively, by the Treating Investigator for both groups. | initial and touch up | 
| Report of Adverse Event | Product safety will be assessed by collection of local tolerability after each injection session, and Adverse Events (AEs) throughout the study. | Day 0, Month 1, Month 3, Month 6, Month 9, Month 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hyaluronic acid, Nasolabial Folds, Dermal filler