RHA® 3 Versus Restylane-L® for Lip Augmentation

Study Overview
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Brief Summary
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This is a multicenter, double-blinded, randomized, prospective, controlled clinical study to identify whether RHA® 3 is non-inferior to Restylane-L® for lip augmentation at Week 12 after the last treatment (initial or touch-up). At screening, the treating investigator (TI) will evaluate the subject's lip fullness using the validated Teoxane Lip Fullness Scale (5-grade) for eligibility of the subject for the study. At screening, the blinded live evaluator (BLE) will evaluate the subject's lip fullness using the TLFS to confirm eligibility and to establish a pre-treatment score for assessment of effectiveness. Enrolled subjects will be randomly assigned in a 3:1 ratio to either the RHA® 3 or the Restylane-L® treatment group. Subjects will be blinded to the study treatment. The TI will administer the fillers, and if necessary, subjects will receive a touch-up treatment 4 weeks after the initial treatment to optimize the results. If the touch-up treatment is administered, the subject will be asked to come to the site for an additional visit 4 weeks after the touch-up injection. The study duration was extended from 36 to 52 weeks once all subjects had already been enrolled. Nearly 60% of the subjects consented to extend the study to 52 weeks before being eligible for repeat treatment. All data are presented up to 52 weeks (as well as 4 more weeks follow-up after retreatment at 36 or 52 weeks). Subjects will be followed for 36 to 52 weeks after their last treatment (initial treatment or touch-up), at which point, they will be offered re-treatment with RHA® 3, regardless of their original treatment, provided that the TI deems the treatment to be appropriate and the subject agrees. Reasons for not administering the re-treatment will be documented. The subject will then be followed for an additional 4 weeks before exiting the study. If the subject or the TI declines re-treatment, this visit (36 or 52 weeks after the last treatment) will be considered the study Exit visit. For subjects with re-treatment, the Exit visit will be 4 weeks after the re-treatment. The TI will conduct safety and effectiveness evaluations at each study visit (up to 36 weeks or 52 (if applicable) weeks after the last treatment, and 4 weeks after re treatment) or until all treatment-related ongoing adverse events (AEs) have resolved or resolved with sequelae as per TI judgment or if follow-up is no longer possible.

Official Title
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A Controlled, Randomized, Double-blinded, Between-subject, Multicenter, Prospective Clinical Study to Evaluate Safety and Effectiveness of RHA® 3 Versus Restylane-L® for Lip Augmentation

Conditions
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Lip Augmentation, Lip

Intervention / Treatment
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* Device: RHA 3
* Device: Restylane-L


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatient, male or female of any race, 22 years of age or older Lip fullness of grade 1 to 3 on the TLFS (ranging from 1 to 5) who desire at least 1 point of correction for upper and/or lower lips OR has Fitzpatrick skin type V or VI and has lip fullness grade 4 or 5 on the TLFS who desire treatment to the vermillion body for upper and/or lower lips. The BLE and TI must independently assess and agree that this criterion is met; however, concordance of fullness is not required. If the assessments of the TI and the BLE are the same or differ by exactly 1 point on the scale, this difference is considered acceptable. If the assessments differ by 2 points or more on the scale, the subject will not be eligible. Willing to abstain from facial aesthetic procedures/therapies that could interfere with study evaluations Able to follow study instructions and complete all required visits. Sign the IRB-approved ICF, Photographic Release Form and the Authorization for Use and release of Health and Research Study Information (HIPAA) form prior to any study- related procedures being performed. Exclusion Criteria: Female subjects that are pregnant, breast-feeding or of childbearing potential and not practicing reliable birth control Known hypersensitivity/allergy to any component of the study devices Clinically significant active skin disease within 6 months Has a history of or currently has an auto-immune disease.

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RHA 3<br>Injection of RHA 3 into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks, optional retreatment at 36 or 52 Weeks. | Device: RHA 3<br>* Investigational Product, RHA® 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogenous, and biodegradable gel implant. It is formulated with sodium hyaluronic acid (NaHA) at a concentration of 23 mg/g obtained from bacterial fermentation using the Streptococcus equi bacterial strained, crosslinked with 1,4 butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.<br>|
| Active Comparator: Restylane- L<br>Injection of Restylane- L into into the vermillion body, vermillion border, and oral commissures of the lips (up to 3 ml with a max of 1.5 ml per lip), injected into the lip mucosa and/or mid to deep dermis as appropriate for lip augmentation. Optional touch up treatment provided at 4 Weeks. | Device: Restylane-L<br>* Comparator Product, Restylane-L is a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TLFS Score (Teoxane Lip Fullness Scale) Between Baseline and Week 12 After Last Treatment of RHA®3 Versus Control Device, as Assessed by the BLE | A change in the TLFS ≥1 grade compared to pre-treatment will be considered clinically meaningful. The TLFS is a validated 5-point scale for assessing lip augmentation. Possible scores range from 1 (Very Thin) to 5 (Very Full). Change = (Week 12 - Baseline score). | Week 12 after last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in TLFS Score as Assessed by the BLE at Visit 5 (Weeks 24 After Last Treatment), 6 (Weeks 36 After Last Treatment), 7 (Week 52 After Last Treatment) if Applicable, and Re-treatment (4 Weeks After Re-treatment) | A change in the TLFS ≥1 grade compared to pre-treatment will be considered clinically meaningful. The TLFS is a validated 5-point static scale for assessing lip augmentation. Possible scores range from 1 (Very Thin) to 5 (Very Full). | Weeks 36 and 52 after last treatment, week 4 after re-treatment | 
| Responder Rate Calculated Using TLFS Assessed by the BLE | A responder will be defined as a subject who has a ≥1 grade improvement on the TLFS. The TLFS is a validated 5-point static scale for assessing lip augmentation. Possible scores range from 1 (Very Thin) to 5 (Very Full). | Weeks 12, 36, 52 after last treatment, week 4 after re-treatment | 
| Number of Subjects Satisfied or Very Satisfied With Study Treatment Using the Subject Satisfaction Scale at Weeks 12, 36, 52 After Last Treatment and 4 Weeks After Re-treatment. | The Subject Satisfaction Scale is a subjective, balanced, 5-point scale assessing subject satisfaction with study treatment. Possible scores range from with 1 (very satisfied) to 5 (very dissatisfied). | Weeks 12, 36, 52 after last treatment and 4 week after re-treatment. | 
| Subject's Perception of Treatment Effectiveness as Per the Satisfaction With Lips FACE-Q | Aesthetics© Scale Questionnaire at Weeks 12, 36, 52 After Last Treatment and 4 Week After Re-treatment. | The FACE-Q measures the experience and outcomes of aesthetic facial procedures from the patient's perspective. The FACE-Q questionnaire is composed of 10 questions with a score linked to answers (1 being Very Dissatisfied and 4 being Very Satisfied). The subject will be instructed as follows: These questions ask about how you look right now. For each question, circle only one answer. With your lips in mind, in the past week, how satisfied or dissatisfied have been with:, and will provide response. To calculate the FACE-Q, outcomes from all 10 questions were pooled, data were transformed so that higher scores reflected a superior (positive) outcome, and adapted to a scale of 100 units (i.e. worst/lowest score = 0, best/highest score = 100). | Change from Baseline at Weeks 12, 36, 52 after last treatment and 4 week after re-treatment. | 
| Subject's Perception of Treatment Effectiveness as Per the Satisfaction With Outcome FACE-Q | Aesthetics© Scale Questionnaire at Weeks 12, 36, 52 After Last Treatment and 4 Week After Re-treatment. | The FACE-Q measures the experience and outcomes of aesthetic facial procedures from the patient's perspective. The FACE-Q questionnaire is composed of 6 questions with a score linked to answers (1 being Definitely disagree and 4 being Definitely agree). The subject will be instructed as follows: We would like to know how you feel about your most recent procedure. For each question, select only one answer. Please indicate how much you agree or disagree with each statement:, and will provide response. To calculate the FACE-Q, outcomes from all 16questions were pooled, data were transformed so that higher scores reflected a superior (positive) outcome, and adapted to a scale of 100 units (i.e. worst/lowest score = 0, best/highest score = 100). | Weeks 12, 36, 52 after last treatment and 4 week after re-treatment. | 
| Number of Subjects Scored Either Much Improved or Improved on Global Aesthetic Improvement (GAI) Scale by the BLE. | The Global Aesthetic Improvement (GAI) is a subjective, balanced, 5-point dynamic scale assessing cosmetic improvement. Possible scores range from much improved, improved, no change, worse, to much worse. The GAI will be assessed using the baseline photograph. | Weeks 12, 36, 52 after last treatment, and 4 weeks after re-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dermal Filler, Hyaluronic acid, Lip, Lip Augmentation