TEOSYAL® RHA Ultra Deep and Perlane-L® for the Correction of Nasolabial Folds

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness and safety of TEOSYAL® RHA Ultra Deep versus Perlane-L® in the treatment of moderate to severe nasolabial folds. This is a controlled, randomized, double-blinded, within subject (split-face), multicenter, prospective clinical study.

Official Title
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A Controlled, Randomized, Double-Blinded, Within-Subject, Multicenter, Prospective Clinical Study of TEOSYAL® RHA (Resilient Hyaluronic Acid) Ultra Deep Versus Perlane-L® in the Treatment of Moderate to Severe Nasolabial Folds

Conditions
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Nasolabial Folds, Wrinkles

Intervention / Treatment
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* Device: TEOSYAL® RHA Ultra Deep


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; female subjects of childbearing potential must have a negative Urine Pregnancy Test and practice a reliable method of contraception; NLFs classified as WSRS grade 3 or 4 (same score for each side); Willing to abstain from facial aesthetic procedures/therapies that could interfere with study evaluations; Able to follow study instructions and likely to complete all required visits; Signed informed consent and HIPAA form. 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 sensitivity to local anesthetics of the amide type, history of multiple severe allergies, history of anaphylactic shock; Known susceptibility to keloid formation, hypertrophic scarring or clinically significant skin pigmentation disorders; Clinically significant active skin disease within 6 months; History of active chronic debilitating systemic disease; History of connective tissue disease; History of malignancy (excl. non-melanoma skin cancer) within past 5 years; History of bleeding disorders; Need for clinically significant and continuous medical treatment within 2 weeks prior to first visit; Received/used a prohibited treatment/procedure within certain time periods (e.g., bioresorbable fillers, NSAIDS, ASA, high dose vitamin E, corticosteroids, interferon, anti-coagulation therapies, laser/light therapies, botulinum toxin injections (frontalis and glabella complex treatment permitted), prescription strength topical retinoids, facial peels, excisional facial surgery, clinically significant oral or maxillofacial surgery). Evidence of clinically significant alcohol or drug abuse, or history of poor cooperation, non-compliance with medical treatment, or unreliability Exhibit a physical attribute(s) that may prevent assessment or treatment of NLFs such as excessive facial hair, traumatic or surgical facial scars, and/or excessive hyperpigmentation in the treatment areas. A condition or situation that may put the subject at significant risk, confound the study results, or significantly interfere with the subject participation.

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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No

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: Left side TEOSYAL® RHA Ultra Deep, Right side Perlane-L®<br>Split-face injection of TEOSYAL® RHA Ultra Deep into the left Naso Labial Folds (NLFs) and Perlane-L® into the right NLF (n=120). Up to 3.0 mL injected per NLF. Touch-up treatment provided at 2 weeks (up to 3.0 mL per NLF). | Device: TEOSYAL® RHA Ultra Deep<br>* 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. It is supplied in individual treatment syringes with 27Gauge ½ disposable sterile needles.<br>|
| Experimental: Left side Perlane-L®, Right side TEOSYAL® RHA Ultra Deep<br>Split-face injection of Perlane-L® into the left Naso Labial Folds (NLFs) and TEOSYAL® RHA Ultra Deep into the right NLF (n=120). Up to 3.0 mL injected per NLF. Touch-up treatment provided at 2 weeks (up to 3.0 mL per NLF). | Device: TEOSYAL® RHA Ultra Deep<br>* 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. It is supplied in individual treatment syringes with 27Gauge ½ disposable sterile needles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-inferiority of the Delta of the WSRS Score Between W24 and Baseline for TEOSYAL® RHA Ultra Deep Versus Perlane-L® for the Correction of Moderate to Severe Naso-Labial Folds Based on the Wrinkle Severity Rating Scale (WSRS) Score Assessed by the BLE. | WSRS (Wrinkle Severity Rating Scale) is a validated 5-point scale with 1 being 'absent' and 5 being 'extreme'. BLE =Blinded Live Evaluator | Baseline and 24 weeks after last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post Injection Treatment Responses (From Common Treatment Responses (CTR) Diary) for Safety Evaluation of TEOSYAL® RHA Ultra Deep Versus Perlane-L® | The subjects received 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 each treatment (initial, touch-up). The diary was discussed during each telephone follow-up visit. Subjects should complete the diary at approximately the same time each day (i.e., am or pm). The subject diary captured 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 included 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 (D0) and touch-up (2 weeks) | 
| Assessment of Injection Site Pain (Visual Analog Scale) of TEOSYAL® RHA Ultra Deep Versus Perlane-L® | VAS is a 100 mm Visual Analog Scale with 0 meaning no pain and 100 meaning intolerable pain | During Injection and 5, 15, 30 minutes post-injection | 
| Delta of the WSRS Score Between W24,36,52 and 64 and Baseline for TEOSYAL® RHA Ultra Deep Versus Perlane-L® for the Correction of Moderate to Severe NLFs Based on the Wrinkle Severity Rating Scale (WSRS) Score Assessed by the Blinded Live Evaluator (BLE) | WSRS (Wrinkle Severity Rating Scale) is a validated 5-point scale with 1 being 'absent' and 5 being 'extreme'. | Baseline and Weeks 24, 36, 52, 64 | 
| Delta of the WSRS Score Between W2,4,12,24,36,52,64 and Baseline for TEOSYAL® RHA Ultra Deep Versus Perlane-L® for the Correction of Moderate to Severe NLFs Based on the Wrinkle Severity Rating Scale (WSRS) Score Assessed by the Treating Investigator (TI) | WSRS (Wrinkle Severity Rating Scale) is a validated 5-point scale with 1 being 'absent' and 5 being 'extreme'. | Baseline and Weeks 2, 4, 12, 24, 36, 52, 64 | 
| Percentage of Responders Based on the Intra-individual Improvement of at Least One Grade in the Wrinkle Severity Rating Scale (WSRS) Compared to Baseline Assessed by the BLE | A responder correspond to a subject with an intra-individual improvement of at least one grade in the WSRS compared to Baseline | Baseline and Weeks 24, 36, 52, 64 | 
| Percentage of Responders Based on the Intra-individual Improvement of at Least One Grade in the Wrinkle Severity Rating Scale (WSRS) Compared to Baseline Assessed by the TI | A responder correspond to a subject with an intra-individual improvement of at least one grade in the WSRS compared to baseline | Baseline and Weeks 2, 4, 12, 24, 36, 52, 64 | 
| Number of Subjects Scored Either Much Improved or Improved on Global Aesthetic Improvement (GAI) by the Blinded Live Evaluator (BLE) | Global Aesthetic Improvement (GAI) is a subjective 5-grade scale comprised of much improved, improved, no change, worse, and much worse. GAI was assessed using the baseline photograph. Each side of the face was assessed independently. | Weeks 24, 36, 52, 64 | 
| Number of Global Aesthetic Improvement (GAI) Responders (i.e., Scoring Either Much Improved or Improved) on GAI Scale. | Global Aesthetic Improvement (GAI) is a subjective 5-grade scale comprised of much improved, improved, no change, worse, and much worse. GAI was assessed using the baseline photograph. Subjects will be instructed: Use a mirror to compare your face to the photograph provided to you and rate the degree of aesthetic improvement by using the following scale. Each side of the face was assessed independently. | Weeks 4, 12, 24, 36, 52, 64 | 
| Subject's Perception of Treatment Effectiveness as Per the FACE-Q (NLF Domain) Questionnaire | The FACE-Q measures the experience and outcomes of aesthetic facial procedures from the patient's perspective. FACE-Q questionnaire is composed of 5 questions with a score linked to answers (1 being 'Not at all' and 4 being 'Extremely'). The subject was instructed as follows: These questions ask about how you look right now. With your nasolabial folds in mind (the deep lines that run downward from the sides of your nose), in the past week, how much have you been bothered by:, and provided response. How deep your nasolabial fold are? How your nasolabial folds look when your face is relaxed (still)? How old your nasolabial folds make you look? How your nasolabial folds look when you smile? How your nasolabial folds look compared with other people your age? To calculate the FACE-Q, outcomes from all 5 questions were pooled and adapted to a scale to 100 units. Data were also transformed so that higher scores reflected a beneficial outcome. | Immediately post-injection, and weeks 2, 4, 12, 24, 36, 52, 64 | 
| Subject's Satisfaction Score | Subjective 5-point scale with 1 being 'very satisfied' and 5 being 'very dissatisfied' | Weeks 2, 4, 12, 24, 36, 52, 64 | 
| Volume to Obtain Optimal Cosmetic Result (Initial Treatment + Touch-up) |  | Week 2 | 
| Number of Subjects Receiving Touch-up Treatment |  | Week 2 | 
| Number of Subjects Receiving Re-treatment |  | Weeks 24, 36, 52, 64 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dermal filler, Nasolabial folds, Hyaluronic acid (HA), Wrinkles