RHA Redensity - Perioral Rhytids

Study Overview
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Brief Summary
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Randomized, blinded, No-Treatment control, multi-center, prospective clinical study, to identify whether TEOSYAL RHA® Redensity is more effective than No-Treatment in the correction of moderate to severe dynamic perioral rhytids at Week 8 after last treatment (i.e., initial or touch-up treatment). The Treating Investigator (TI) at screening will evaluate the subject's perioral rhytids severity using the Perioral Rhytids Severity Rating Scale (PR-SRS) for eligibility of the subject for the study. The Blinded Live Evaluator (BLE) at screening will evaluate the subject's perioral rhytids severity using the PR-SRS in order to confirm eligibility and to establish a pre-treatment (Baseline) score for assessment of effectiveness. This is done independently of the TI, and exact concordance between the BLE and the TI is not necessary for eligibility of the subject in this study. Enrolled subjects will be randomized to either the TEOSYAL RHA® Redensity treatment group or the No-Treatment control group (ratio 3:1). The TI will administrate the study device, and if necessary, subjects will receive a touch-up treatment 14 days following the initial treatment to optimize the results. The TI will conduct safety and effectiveness evaluations at study visits, which occurred at Week 4, 8, 12, 16, 24, 36, and 52 after the last treatment, (i.e., initial or touch-up treatment) and 4 weeks after a Repeat-Treatment. The Blinded Live Evaluator (BLE) will conduct assessments of effectiveness during the trial, including assessment of the primary endpoint at Week 8 after the last treatment (i.e., initial or touch-up treatment). The BLE will conduct effectiveness evaluations at Week 8, 12, 16, 24, 36, and 52 after the last treatment (i.e., initial or touch-up treatment). All subjects will be followed for 52 weeks after the last treatment (i.e., initial treatment or touch-up), at which point they will be offered Repeat-Treatment (provided that the TI deems the treatment to be appropriate and the subject agrees) and will be then followed for 4 weeks after Repeat-Treatment before exiting the study. If a subject returns to his pre-treatment PR-SRS score at Week 12 or Week 16 or Week 24 or Week 36 after initial treatment or touch up (as assessed by the TI), subjects are eligible for optional Early-Retreatment if necessary at 12 or 16 or 24 or 36 weeks after last treatment (provided that the TI deems the treatment appropriate, and the subject agrees). Subjects will be then followed for an additional 4 weeks after Repeat-Treatment. Subjects who will receive optional Early-Retreatment at Week 12 or Week 16 or Week 24 or Week 36 after the after initial treatment or touch-up, will be offered Repeat-Treatment at Week 52. Subjects randomized to the No-Treatment control group will receive their first treatment after the primary endpoint evaluation (Week 8 after randomization) and then will be followed the same schedule as the initial treatment group.

Official Title
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A Randomized, Blinded, No-Treatment Control, Multicenter, Prospective Clinical Study of TEOSYAL RHA® Redensity for the Treatment of Moderate to Severe Dynamic Perioral Rhytids

Conditions
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Perioral Rhytids, Aging, Wrinkle

Intervention / Treatment
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* Device: TEOSYAL RHA Redensity


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 Moderate to severe perioral rhytids of grade 2 or 3 on the four-point PR-SRS (ranging from 0-3) 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 Known susceptibility to keloid formation, hypertrophic scarring or clinically significant skin pigmentation disorders Clinically significant active skin disease within 6 months History of connective tissue 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEOSYAL RHA Redensity<br>Injection of TEOSYAL RHA Redensity into the perioral lines (n=150). Up to 6.0 mL (max 3 mL for upper and max 3 mL for lower) injected into the dermis, including the superficial dermis. Touch-up treatment provided at 2 weeks. | Device: TEOSYAL RHA Redensity<br>* A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of streptococcus zooepidemicus, formulated to a concentration of 15 mg/g and 0.3% w/w lidocaine in a physiologic buffer.<br>|
| No Intervention: No Treatment<br>No treatment control group (n=52). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Perioral Rhytids Severity Rating Scale (PR-SRS) Score Rated by the Blinded Live Evaluator (BLE) at Week 8 After Last Treatment. | The PR-SRS is a validated 4-point static scale for assessing perioral rhytids severity. Possible scores range from 0 (Absent) to 3 (Severe). Change = (Week 8 - Baseline score). A PR-SRS change of 1-grade will be considered clinically significant. The No-Treatment control group after treatment was not pooled for this primary outcome measure. | Week 8 after last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject's Perception of Treatment Effectiveness as Per the FACE-Q Scale (Perioral Rhytid Domain) Questionnaire at Baseline, Weeks 4 and 8 After Last 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 'Not at all' and 4 being 'Extremely'). To calculate the FACE-Q score, outcomes from all 6 questions were pooled, data were transformed so that higher scores reflected a superior outcome and adapted to a 100- unit scale. The No-Treatment control group after treatment was not pooled for this secondary outcome measure. | Baseline, Weeks 4 and 8 after last treatment | 
| Number of Subjects Who Scored Themselves Either Much Improved or Improved on Global Aesthetic Improvement (GAI) Scale at Week 8 and 4 After Last Treatment. | 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 pre-injection baseline photograph. The No-Treatment control group after treatment was not pooled for this secondary outcome measure. | Weeks 4 and 8 after last treatment | 
| Number of Subjects Scored Either Much Improved or Improved on Global Aesthetic Improvement (GAI) Scale by the Blinded Live Evaluator (BLE) at Week 8 After Last Treatment. | 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 pre-injection baseline photograph. The No-Treatment control group after treatment was not pooled for this secondary outcome measure. | Week 8 after last treatment | 
| Number of Subjects Satisfied or Very Satisfied With Study Treatment Using the Subject Satisfaction Scale at Week 8 After Last 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). The No-Treatment control group after treatment was not pooled for this secondary outcome measure. | Week 8 after last treatment | 
| Number of Participants With Adverse Events for the Safety Evaluation of TEOSYAL RHA® Redensity. | The Treating Investigator will assess adverse events and record details of seriousness, severity, duration, and action taken with the study device, and relationship to the study device. AEs will be reported from the time of consent until week 52 or to 1 month following the last treatment. | Baseline through Week 52 following the last treatment and 4 weeks following re-treatment | 
| Number of Post-Injection Treatment Responses (From Common Treatment Responses (CTR) Diary) for the Safety Evaluation of TEOSYAL RHA® Redensity. | The subjects will receive a diary booklet and instructions for recording his/her observations of the Common Treatment Responses of the study treatments for the first 14 days after treatment. The diary will be discussed during telephone follow-up visit. Subjects should complete the diary at approximately the same time each day (i.e., am or pm). The subject diary captures the following Common Treatment Responses (CTR) that occur following the injection of a dermal filler; specifically, redness, pain, tenderness, firmness, swelling, lumps/bumps, bruising, itching, discoloration, and other. The 14-day patient CTR diary includes a detailed glossary describing all signs/symptoms listed in the diary; an option was provided to rate other if the subject experienced a sign/symptom that is not listed. The table presents the number of subjects experiencing at least 1 Common Treatment Response (CTR). | During 14 days after initial treatment and touch-up (2 weeks) | 
| Assessment of Injection Site Pain Felt by the Patient for the Safety Evaluation of TEOSYAL RHA® Redensity. | The Injection Site Pain (during injection and post-injection) will be self-assessed by the subject using a 100 mm Visual Analog Scale (VAS). VAS is a 100 mm Visual Analog Scale with 0 meaning no pain and 100 meaning intolerable pain. | Baseline, Weeks 2, 12, 16, 24, 36 and 52 | 
| Assessments of the Lip Function (Lip Movement) by the Treating Investigator (TI) for the Safety Evaluation of TEOSYAL RHA® Redensity. | This Lip functionality testing was conducted by the Treating Investigator (TI) at each follow-up visit and pre- and post-injection at each injection, which occurred at Baseline, Weeks 2, 4, 8, 12, 16, 24, 36, and 52 after the last treatment. | Baseline, Weeks 2, 4, 8, 12, 16, 24, 36, and 52 after the last treatment, (i.e., initial or touch-up treatment) and 4 weeks after a Repeat-Treatment. | 
| Assessments of the Lip Function by the Treating Investigator (TI) for the Safety Evaluation of TEOSYAL RHA® Redensity. | This Lip functionality testing was conducted by the Treating Investigator (TI) at each follow-up visit and pre- and post-injection at each injection, which occurred at Baseline, Weeks 2, 4, 8, 12, 16, 24, 36, and 52 after the last treatment. | Baseline, Weeks 2, 4, 8, 12, 16, 24, 36, and 52 after the last treatment, (i.e., initial or touch-up treatment) and 4 weeks after a Repeat-Treatment. | 
| Assessments of the Lip Function by the Treating Investigator (TI) for the Safety Evaluation of TEOSYAL RHA® Redensity. | This Lip functionality testing was conducted by the Treating Investigator (TI) at each follow-up visit and pre- and post-injection at each injection, which occurred at Baseline, Weeks 2, 4, 8, 12, 16, 24, 36, and 52 after the last treatment. Lip sensation | Baseline, Weeks 2, 4, 8, 12, 16, 24, 36, and 52 after the last treatment, (i.e., initial or touch-up treatment) and 4 weeks after a Repeat-Treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perioral rhytids, Dermal filler, Hyaluronic acid, Aging, Wrinkle