RHA® 4 With New Anesthetic - Nasolabial Folds

Study Overview
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Brief Summary
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This is a randomized, controlled, double-blinded, within-subject (split-face), multicenter, prospective study to investigate whether RHA® 4 with New Anesthetic Agent is non-inferior to RHA® 4 (with lidocaine) in terms of injection site pain felt by the subject during injection. At screening, the Treating Investigator (TI) evaluated subjects' NLF severity (using the Wrinkle Severity Rating Scale; WSRS) to confirm eligibility and to establish a pre-treatment score for assessing aesthetic improvement. At Visit 1, RHA® 4 With New Anesthetic Agent was administered in a random sequence (first or second injection) and side of the face (left or right) and RHA® 4 with lidocaine was administered to the other side. Study subjects and the TI injecting study devices were blinded. Immediately after injection of each side, subjects rated injection site pain experienced during injection using a 100 mm Visual Analog Scale (VAS). Injection site pain in each side of the face was also assessed at 15, 30, 45 and 60 minutes post-injection. Safety evaluation consisted of AE assessments, a 30-day CTR (Common Treatment Response) diary and a follow-up call performed by the study site at 72 hours after injection. Subjects attended Visit 2 (30 days post-injection) where efficacy and safety assessments will be conducted. Subjects who present with an unresolved clinically significant device related AE at Visit 2 received the optional follow-up phone call no later than 30 days after Visit 2. If the clinically significant AE remained unresolved, the Investigator requested that the subject attended the optional in-clinic follow-up visit (i.e., Visit 3) within 5 working days. Follow-up of the clinically significant AE continued until the AE was resolved or the TI determines that additional follow-up was not necessary.

Official Title
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A Randomized, Controlled, Double-blinded, Within-subject (Split-face), Multicenter, Prospective Clinical Study to Compare the Level of Pain Using the Dermal Filler RHA® 4 Formulated With Two Different Anesthetics in the Treatment of Nasolabial Folds

Conditions
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Aging, Pain

Intervention / Treatment
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* Device: RHA®4 with new anesthetic agent
* Device: RHA®4-Lidocaine


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 UPT at Visit 1 and practice a reliable method of contraception throughout the study. Moderate to severe bilateral nasolabial folds (grade 3 or 4 on the five-point WSRS). Nasolabial folds of the same WSRS grade on the left and right sides of the face. Able to follow study instructions and complete all required visits. Sign the IRB-approved ICF, Photographic Release Form, the Authorization for Use and release of Health and Research Study Information (HIPAA) form, and if applicable the California Experimental Research Subject's Bill of Rights prior to any study-related procedures being performed. Exclusion Criteria: Female subjects who are pregnant, breast-feeding, or of childbearing potential and not practicing reliable birth control. Known hypersensitivity or previous allergic reaction to any component of the study devices. Use of a prohibited treatment/procedure within time periods defined in the protocol 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. Malignancy (excluding non-melanoma skin cancer) within the past 5 years. History of skin cancer in the treatment area. Clinically active disease or infection in the NLF area. Medical or psychiatric conditions that may increase the risk associated with study participation or may interfere with the interpretation of study results or compliance of the subject and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study. 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.

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
Interventional Model Description: Split-face design
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RHA®4 with new anesthetic agent<br>Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. | Device: RHA®4 with new anesthetic agent<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 23 mg/g and 0.3% w/w of new anesthetic agent in a physiologic buffer.<br>|
| Experimental: RHA®4-Lidocaine<br>Split-face injection of RHA®4 with new anesthetic agent in the nasolabial fold of one side of the face and RHA®4-Lidocaine in the nasolabial fold of opposite side of the face. Up to 3 mL injected per side. | Device: RHA®4-Lidocaine<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 23 mg/g and 0.3% w/w lidocaine in a physiologic buffer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-inferiority of RHA® 4 With New Anesthetic Agent Versus RHA® 4-Lidocaine in Terms of Reducing Pain During Device Injection Into Nasolabial Folds. | Injection pain during injection will be based on the 100 mm Visual Analog Scale (VAS), as assessed by subjects immediately after injection of each nasolabial fold. VAS is a 100 mm Visual Analog Scale with 0 meaning no pain and 100 meaning intolerable pain. | Visit 1 - During Injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference Between RHA® 4 With New Anesthetic Agent Versus RHA® 4-Lidocaine in Term of Reducing Pain at 15, 30, 45 and 60 Minutes Post-injection in Nasolabial Folds of Each Side of the Face. | Injection pain was measured on the 100 mm Visual Analog Scale (VAS), as assessed by subjects in nasolabial fold of each side of the face. VAS is a 100 mm Visual Analog Scale with 0 meaning no pain and 100 meaning intolerable pain | Visit 1 - 15, 30, 45 and 60 minutes post-injection | 
| Change in NLF WSRS Score Between Baseline and Day 30 as Assessed by the Treating Investigator | NLF-WSRS (Nasolabial Folds- Wrinkle Severity Rating Scale) is a validated 5-grade scale with 1 being Absent and 5 being Extreme | Visit 1 - Baseline (pre-injection), Visit 1 (post-injection), Visit 2 (Day 30) | 
| Percentage of Responders Based on the Intra-individual Improvement of at Least One Grade on the Nasolabial Folds Wrinkle Severity Rating Scale (NLF-WSRS) Compared to Baseline, as Assessed by the TI | A responder corresponds to a subject with an intra-individual improvement of at least one grade on the NLF WSRS compared to Baseline, as assessed by the TI | Visit 1 (Baseline, pre-injection), Visit 1 (post-injection), Visit 2 (Day 30) | 
| Subject's Perception of Treatment Effectiveness as Per the FACE-Q (Nasolabial Folds 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 will be instructed as follows: These questions ask about how you look right now. For each question, circle only one answer. 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 will provide response. To calculate the FACE-Q, outcomes from all 5 questions were pooled, data were transformed so that higher scores reflected a superior outcome, and adapted to a scale of 100 units (i.e. lowest score = 0, highest score = 100). | Visit 1 (Baseline) and Visit 2 (Day 30) | 
| Number of Subjects Scored Either Much Improved or Improved on Global Aesthetic Improvement (GAI) by the Treating Investigator (TI) | 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 will be assessed independently. | Visit 1 (just after receiving treatment) and Visit 2 (Day 30) | 
| Number of Global Aesthetic Improvement (GAI) Responders (i.e., Scoring Either Much Improved or Improved) on GAI Scale According to Subject's Self-assessment | 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 were 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. | Visit 1 (just after receiving treatment) and Visit 2 (Day 30) | 
| Number of Subjects Satisfied or Very Satisfied With Study Treatment Using the Subject's Satisfaction Scale | 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). Proportion of subjects who were Satisfied (i.e., 1-Very Satisfied + 2-Satisfied) was compared to the proportion of subjects who were Not Satisfied (i.e., 3-Neither Satisfied nor dissatisfied + 4-Dissatisfied + 5-Very Dissatisfied) | Visit 1 (just after receiving treatment) and Visit 2 (Day 30) | 
| Number of Subjects With Post Injection Treatment Responses (From Common Treatment Responses (CTR) Diary) for Safety Evaluation of RHA® 4 With New Anesthetic Agent Versus RHA® 4-Lidocaine | The subjects received a diary booklet and instructions for recording their observations of the Common Treatment Responses to the study treatments during 30 days following the injection. The diary were discussed during follow-up phone call and visit. Subjects were instructed to 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 30-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. | During 30 days after injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyaluronic Acid, Anesthetic, Lidocaine, Nasolabial Folds