RHA®4 for Midface Volume Deficiency

Teoxane SA201 enrolled

Overview

This is a prospective, randomized, controlled, blinded evaluator, multicenter, between subjects clinical study to identify whether RHA4 is non-inferior to a comparator device for treatment of midface volume deficiency 8 weeks after the last treatment (initial or touch-up). At Screening, the treating investigator (TI) and the Blinded Live Evaluator (BLE) will evaluate independently the subject's midface using the validated 5-grade Teoxane Midface Volume Deficit Scale (TMVDS) for eligibility of the subject for the study. The BLE will establish a pretreatment score for assessment of effectiveness. If the assessments of the TI and the BLE are the same or differ exactly by 1 point of the scale, the difference will be considered acceptable. The TI and the BLE need to agree that the subject meets the eligibility criterion (TMVDS grade 2 to 3). If the subject is eligible, the BLE's assessment will be used for the Baseline of the primary endpoint. Eligible subjects will be enrolled and randomly assigned in a 3:1 ratio at Screening to receive RHA4 or comparator product. The TI will administer the fillers, and if necessary, subjects will receive a touch-up treatment with the same product that they received on Visit 1, 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. Subjects will be followed for 52 weeks after their last treatment (initial treatment or touch-up), at which point, they will be offered re-treatment with RHA® 4, 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 12 weeks before exiting the study. If the subject or the TI declines re-treatment, this visit (52 weeks after the last treatment) will be considered the study Exit visit. For subjects with re-treatment, the Exit visit will be 12 weeks after the re-treatment. The TI will conduct safety and effectiveness evaluations at each study visit, which will occur: at 4 weeks after the initial and touch-up treatment, 8, 24, and 52 weeks after the last treatment, and 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. A follow-up telephone call for safety will be performed 3 days after each treatment. Subjects will report their common treatment responses (CTRs) in a subject diary for 30 days after each injection. The diary will also include a list of selected AEs potentially associated with injection of dermal fillers for subjects to report if applicable. All efforts should be made by the TI to schedule the applicable visits to allow completion of the CTR diary. A BLE will conduct assessments of effectiveness during the study, including assessment of the primary endpoint 8 weeks after the last treatment. The BLE will be blinded to allocation to groups (RHA4 group or comparator product group). Furthermore, to ensure that they remain blinded and unbiased when making their assessments throughout the study, the BLE, TI, and subjects will not be allowed to refer to each other's effectiveness assessments. All subjects will be instructed to not discuss their study treatment, AEs, or CTRs with the BLE.

Interventions

injection of RHA®4 in MidfaceDEVICE

RHA® 4 is a sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus equi bacteria, formulated to a concentration of 23 mg/mL and 0.3% w/w lidocaine in a physiologic buffer. Up to 3.0 mL injected per cheek (subcutaneous and/or supraperiosteal layer). Touch-up treatment provided at 4 weeks (up to 3.0 mL per cheek).

injection of Comparator Product in MidfaceDEVICE

Comparator product is sterile, biodegradable, colorless gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE. Up to 3.0 mL injected per cheek (subcutaneous and/or supraperiosteal layer). Touch-up treatment provided at 4 weeks (up to 3.0 mL per cheek).

Eligibility

Sex: ALLMin age: 22 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Outpatient, male or female of any race, 22 years of age or older * Female subjects of childbearing potential must have a negative UPT and practice a reliable method of contraception throughout the study. * Seeking treatment of midface volume deficiency (realistic and achievable as per TI opinion) * Having midface volume loss of grades 2 to 3 on the TMVDS (ranging from 0 = absent to 4 = very severe). 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. * Having cheeks of the same TMVDS grade on the left and right side of the face (i.e., approximate bilateral symmetry) * 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: * Known hypersensitivity or previous allergic reaction to any component of the study devices. * Known sensitivity to local anesthetics of the amide type, history of multiple severe allergies, or history of anaphylactic shock. * History of active chronic debilitating systemic disease that, in the opinion of the investigator, would make the subject a poor candidate in the study. * History of connective tissue disease. * Clinically significant alcohol or drug abuse, or history of poor cooperation or unreliability. * Exposure to any other investigational drug/device within 90 days of entering the study or planning to participate in another investigation during the course of the study.

Outcomes

Primary Outcomes

Non-inferiority of RHA®4 to the Change From Baseline for Subjects Treated With Comparator Product at 8 Weeks After the Last Treatment as Assessed by the BLE Using the Teoxane Midface Volume Deficit Scale (TMVDS).

A change in the TMVDS ≥1 grade compared to pretreatment will be considered clinically meaningful. In order to confirm sensitivity 8 weeks after the last treatment: the proportion of responders with a ≥1-grade point on the TMVDS scale for Comparator product 8 weeks after the last treatment when compared to Baseline must be ≥70%. The TMVDS is a validated 5-point scale for assessing midface volume deficit. Possible scores range from 0 (Absent) to 4 (Very Severe).

Time frame: 8 weeks after the last treatment

Secondary Outcomes

Change From Baseline in TMVDS Score as Assessed by the BLE at 24 and 52 Weeks After Last Treatment,and Weeks After Re-treatment if Applicable.

A change in the TMVDS ≥1 grade compared to pre-treatment will be considered clinically meaningful. The TMVDS is a validated 5-point static scale for assessing midface volume deficit. Possible scores range from 0 (Absent) to 4 (Very Severe).

Time frame: Week 24, 52 after last treatment, week 12 after re-treatment

Number of Subjects Scored Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) Scale by the BLE.

he 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".

Time frame: Week 8, 24, 52 after last treatment, week 12 after re-treatment

Subject's Perception of Treatment Effectiveness as Per the "Satisfaction With Cheeks" FACE-Q Scale Questionnaire at Each Visit, at Rest.

The FACE-Q measures the experience and outcomes of aesthetic facial procedures from the patient's perspective. The FACE-Q questionnaire is composed of 5 questions with a score linked to answers (1 being "Very Dissatisfied" and 4 being "Very Satisfied"). To calculate the FACE-Q score, outcomes from all 5 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).

Time frame: Change from Baseline at Weeks 8, 24, 52 after last treatment,12 weeks after re-treatment

Subject's Perception of Treatment Effectiveness as Per the "Satisfaction With Cheeks" FACE-Q Scale Questionnaire at Each Visit, When Smiling

Time frame: Change from Baseline at Weeks 8, 24, 52 after last treatment and 12 week after re-treatment.

Number of Subjects "Satisfied" or "Very Satisfied" With Study Treatment Using the Subject Satisfaction Scale at Weeks 8, 24, 52 After Last Treatment and 12 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).