This is a randomized, controlled, single-blinded, within-subject (split-face), multicenter, prospective study to investigate whether RHA®4 injected in NLFs with a cannula is non-inferior to RHA®4 injected in NLFs with a sharp needle (27G x ½") for the correction of moderate to severe NLFs as determined by the Blinded Live Evaluator (BLE) using the Teoxyne NLF-WSRS (proprietary, validated NLF Wrinkle Severity Rating Scale) at 12 weeks from last treatment. At Visit 1 (Week 0), RHA®4 injected with cannula will be administered in a random sequence (first or second injection) and side of the face (left or right NLF) and RHA®4 injected with a sharp needle will be administered to the other side. The TI will administer study devices and will be unblinded to treatment allocation. Blinded assessments of effectiveness will be conducted by the BLE (Blinded Live Evaluator). 4 weeks following initial treatment, subjects will attend Visit 2 and receive, if necessary, touch-up treatments (using a needle or cannula as per the subject's initial treatment assignment). Subjects receiving touch-up treatments at Week 4 (Visit 2) will attend a new Visit 2b (4 weeks following touch-up treatment); subject not receiving touch-up treatment will not attend Visit 2b. After each injection (initial treatment or touch-up), subjects will receive a safety follow-up call from the study site within 3-day. Subjects will then attend scheduled in-office study visits at 8 (Visit 3) and 12 weeks (Visit 4) following last treatment (initial treatment or touch-up) where safety and effectiveness assessments will be conducted.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
50
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 NLF (mid-dermis to deep-dermis). Touch-up treatment provided at 2 weeks (up to 3.0 mL per NLF). The brand of cannula used for injection is up to the discretion of the Treating Investigator (TI), providing the cannula is registered for use by the US FDA.
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 NLF (mid-dermis to deep-dermis). Touch-up treatment provided at 2 weeks (up to 3.0 mL per NLF).
United States, California
Encinitas, California, United States
United States, Florida
West Palm Beach, Florida, United States
United States, North Carolina
Chapel Hill, North Carolina, United States
United States, Tennessee
Nashville, Tennessee, United States
Change in NLF-WSRS Score Between Baseline and Week 12 After Last Treatment as Assessed by the BLE
Non-inferiority of RHA®4 injected with a cannula to the change from Baseline for subjects treated with RHA®4 injected with a needle at 12 weeks after last treatment (initial or touch-up; up to 16 weeks post-baseline)) as assessed by the BLE using the NLF-WSRS. NLF-WSRS (Nasolabial Folds - Wrinkle Severity Rating Scale) is a proprietary validated 5-grade scale with 1 being "Absent" and 5 being "Extreme". An NLF-WSRS change of \>1 grade will be considered clinically significant.
Time frame: Week 12 after last treatment
Change in Score From Baseline in the Nasolabial Folds Severity Rated by the Treating Investigator (TI) at Weeks 4, 8 and 12 After Last Treatment Using the NLF-WSRS.
NLF-WSRS (Nasolabial Folds - Wrinkle Severity Rating Scale) is a proprietary validated 5-grade scale with 1 being "Absent" and 5 being "Extreme".
Time frame: Weeks 4, 8 and 12 after last treatment
Number of Responders (Change of ≥1-grade From Baseline in the Naso-labial Folds Severity) as Assessed by the Blinded Live Evaluator (BLE) at Week 12 After Last Treatment Using the NLF-WSRS.
NLF-WSRS (Nasolabial Folds- Wrinkle Severity Rating Scale) is a proprietary validated 5-grade scale with 1 being "Absent" and 5 being "Extreme".
Time frame: Week 12 after last treatment
Number of Responders (Change of ≥1-grade From Baseline in the Naso-labial Folds Severity) as Assessed by the Treating Investigator (TI) at Weeks 4, 8 and 12 After Last Treatment Using the NLF-WSRS.
NLF-WSRS (Nasolabial Folds- Wrinkle Severity Rating Scale) is a validated 5-grade scale with 1 being "Absent" and 5 being "Extreme"
Time frame: Weeks 4, 8 and 12 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 12 Weeks Following 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. Each side of the face will be assessed independently.
Time frame: Week 12 after last treatment
Number of Subjects Scored Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) Scale by the Treating Investigator (TI) at 4, 8 and 12 Weeks Following 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. Each side of the face will be assessed independently.
Time frame: Weeks 4, 8 and 12 after last treatment
Number of Subjects Who Scored Themselves Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) Scale at 4, 8 and 12 Weeks Following 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. Each side of the face was assessed independently. 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".
Time frame: Weeks 4, 8 and 12 after last treatment
Number of Subjects "Satisfied" or "Very Satisfied" With Study Treatment Using the Subject Satisfaction Scale at 4, 8 and 12 Weeks Following 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).
Time frame: Weeks 4, 8 and 12 after last treatment
Subject's Perception of Treatment Effectiveness as Per the FACE-Q | Aesthetics© (Nasolabial Folds Domain) Questionnaire. The FACE-Q Measures the Experience and Outcomes of Aesthetic Facial Procedures From the Patient's Perspective.
The FACE-Q \| Aesthetics© 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 (positive) outcome, and adapted to a scale of 100 units (i.e. worst/lowest score = 0, best/highest score = 100).
Time frame: Weeks 4, 8 and 12 after last treatment
Number of Participants Receiving Initial and Touch-Up Treatment Sessions to Obtain an Optimal Cosmetic Results as Judged by the Treating Investigator
Number of subjects receiving treatment (initial and touch up)
Time frame: Baseline (Week 0, Visit 1) and Touch-up (Week 4, Visit 2)
Total Volume Per NLF to Obtain an Optimal Cosmetic Results as Judged by the Treating Investigator.
Time frame: Baseline (Week 0) and Touch-up (Week 4)
NLF Symmetry as Assessed by the Blinded-live Evaluator at Baseline and 12 Weeks Following Last Treatment.
NLF symmetry will be assessed for right and left NLF by answering the question "Are the NLFs symmetric or asymmetric?" (answer = symmetric or asymmetric answer). If asymmetric, the asymmetry will be further assessed as mild, moderate or severe.
Time frame: Baseline (Week 0) and Week 12 after last treatment
NLF Symmetry as Assessed by the Treating Investigator at Baseline 4, 8 and 12 Weeks Following Last Treatment.
NLF symmetry will be assessed by the TI for right and left NLF by answering the question "Are the NLFs symmetric or asymmetric?" (answer = symmetric or asymmetric answer). If asymmetric, the asymmetry will be further assessed as mild, moderate or severe.
Time frame: Weeks 4, 8 and 12 after last treatment
NLF Symmetry as Assessed by the Subject at Baseline, 4, 8 and 12 Weeks Following Last Treatment.
NLF symmetry will be assessed for right and left NLF by answering the question "Are the NLFs symmetric or asymmetric?" (answer = symmetric or asymmetric answer). If asymmetric, the asymmetry will be further assessed as mild, moderate or severe.
Time frame: Weeks 4, 8 and 12 after last treatment
Number of Participants With Adverse Events (AEs) for the Safety Evaluation of RHA® 4
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 12 of the last treatment. An AE is any untoward medical occurrence in a subject administered the study device and which may, but does not necessarily, have a causal relationship with the device. An AE can therefore be any unfavorable or unintended sign (for example an abnormal laboratory finding), symptom or disease temporally associated with the use the study device, whether or not considered related to that device.
Time frame: Baseline through Week 12 after last treatment
Number of Post-Injection Treatment Responses (From Common Treatment Responses (CTR) Diary) for the Safety Evaluation of RHA® 4.
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 28 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 28-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).
Time frame: During 28 days after initial treatment and touch-up, so a total of 42 days post-baseline if the subject received a touch-up
Assessment at Each Injection Visit (Initial Inejction and Touch-up) of Injection Site Pain Felt by the Patient for the Safety Evaluation of RHA® 4 Immediately After Treatment, and at 5, 30, and 60 Minutes Post-treatment
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.
Time frame: Immediately after treatment, and at 5, 30, and 60 minutes post-treatment
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