Multicenter Double-Blind Randomized Split-Face Study to Evaluate Revanesse® Ultra vs Restylane® for Correction of NLF

A Multicenter, Double-Blind, Randomized, Split-Face Study to Evaluate the Safety and Efficacy of Revanesse® Ultra Versus Restylane® for the Correction of Nasolabial Folds

A randomized, multicenter, double blind, split-face study in subjects seeking NLF correction. Subjects were treated with Revanesse Ultra in the NLF on one side of the face and Restylane in the NLF on the other side of the face. The side of the face for each product was randomly assigned. The investigator performing the evaluations and the subject were blinded to the treatment; injections of the study product were performed by an unblinded injecting investigator.

Study Overview

• Status: Completed
• Conditions: Nasolabial Fold Correction
• Intervention / Treatment: Device: Revanesse Ultra; Device: Restylane

Detailed Description

The study was a randomized, double-blind prospective, comparative study of the efficacy and safety of Revanesse Ultra versus the approved product Restylane in the cutaneous correction of NLFs. Randomization followed a 1:1 within-subject control model of augmentation correction of NLFs. Given that the implants have been shown to not migrate, the within-subject model was ideal and had already been shown in previous studies to detect differences. Subjects with signs of NLFs who met the entry criteria were enrolled. All subjects were followed for efficacy and safety for 6 months. Subjects could have open-label retreatment as needed with Revanesse Ultra at 6 months if their baseline WSRS scores had returned to baseline, or as needed to achieve optimal correction if their baseline WSRS scores had not returned to baseline and were followed for a total of 12 months. The study design was appropriate for the indication studied.

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects must meet all of the following criteria to be eligible for the study:

1. Men or women 22 years of age or older.
2. Two fully visible bilateral nasolabial folds each with a Wrinkle Severity Rating Scale Score of 3 or 4 that may be corrected with an injectable dermal filler.
3. If female and of childbearing potential, a negative urine pregnancy test and agree to use adequate contraception. Female subjects of childbearing potential (excluding women who are surgically sterilized or postmenopausal for at least 2 years) must have a negative urine pregnancy test and must be willing to use a medically accepted method of contraception during the study. The following are considered acceptable methods of birth control for the purpose of this study: oral contraceptives, contraceptive patches, contraceptive implant, vaginal contraceptive, double barrier methods (e.g., condom and spermicide), contraceptive injection (Depo-Provera®), intrauterine device (IUD), hormonal IUD (Mirena®), and abstinence with a documented second acceptable method of birth control if the subject becomes sexually active. Subjects entering the study who are on hormonal contraceptives must have been on the method for at least 90 days prior to the study and continue the method for the duration of the study. Subjects who had used hormonal contraception and stopped must have stopped no less than 90 days prior to Visit 1/Day 1.
4. Ability to understand and comply with the requirements of the study.
5. Willingness and ability to provide written informed consent.

6. Agree to refrain from seeking other treatment for this condition during the study.

   -

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from the study:

1. Wrinkle Severity Rating Scale Score of ≤ 2 on the right or left nasolabial fold.
2. Women who are pregnant or lactating.
3. Received prior dermabrasion, facelift, or Botox below the orbital rim within 6 months (180 days) prior to entry into the study.
4. Previous tissue augmentation (bulking agents) for facial wrinkles and scars within 6 months (180 days) at the proposed injection sites.
5. Previous tissue augmentation with permanent implants.
6. Evidence of scar-related disease or delayed healing activity within the past 1 year.
7. Scars at the intended treatment sites.
8. History of keloid formation or hypertrophic scars.
9. Any infection or wound on the face.
10. Allergic history including anaphylaxis or multiple severe allergies to natural rubber latex or lidocaine.
11. Aspirin or nonsteroidal anti-inflammatory drugs within 1 week (7 days) prior to treatment.
12. Concomitant anticoagulant therapy, antiplatelet therapy, or history of bleeding disorders or connective tissue disorders.
13. Over-the-counter (OTC) wrinkle products or prescription wrinkle treatments within 4 weeks (28 days) prior to treatment and throughout the study.
14. Immunocompromised or immunosuppressed.
15. Clinically significant organic disease including clinically significant cardiovascular, hepatic, pulmonary, neurologic, or renal disease or other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the investigator, preclude participation in the trial.
16. Received any investigational product within 30 days of signing the Informed Consent Form.
17. Facial tattoo that may interfere with diagnosis.

18. Systemic (oral/injectable) corticosteroids or immunosuppressive medications within 30 days prior to treatment and topical steroids on the face within 14 days prior to treatment start and throughout the study.

    -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Revanesse Ultra; Revanesse Ultra in the NLF on one side of the face	Device: Revanesse Ultra; NLF correction
Active Comparator: Restylane; Restylane injection in the NLF on the other side of the face to optimal correction	Device: Restylane; NLF Correction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy Variable is Change From Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) Score	Primary efficacy variable is change from Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) - Treatment success is defined as at least a 1-grade improvement in WSRS from baseline to Week 24 WSRS Score categories: Absent - No visible fold; continuous skin line.; Mild - Shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance.; Moderate - Moderately deep folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected from injectable implant.; Severe - Very long and deep folds; prominent facial feature; less than 2 mm visible when stretched; significant improvement is expected from injectable implant.; Extreme - Extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone.	Visit 6/Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Efficacy Endpoints Are the Responder Rate, Percentage of *Nasolabial Folds* With Treatment Success	Treatment success (defined as at least a 1-grade improvement in WSRS from baseline to Week 24): The WSRS Score is a 5-point scale. The WSRS score was assessed for each NLF at every study visit through Visit 6/Week 24 by a blinded evaluator (blinded to the treatment assignment of each NLF).	Visit 6/Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other Efficacy Variables Include Change in WSRS Score	Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24)	Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12
Other Efficacy Variables Include Change in Patient Global Aesthetic Improvement (pGAI) Score	Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24)	Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12
Other Efficacy Variables Include Change in Investigator Global Aesthetic Improvement (iGAI) Score	Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24)	Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12

Collaborators and Investigators

• Sponsor: Prollenium Medical Technologies Inc.
• Investigators: Principal Investigator: Michael H Gold, MD, Tennessee Clinical Research Center

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: December 5, 2016
• First Submitted That Met QC Criteria: December 6, 2016
• First Posted (Estimate): December 8, 2016

Study Record Updates

• Last Update Posted (Actual): February 22, 2018
• Last Update Submitted That Met QC Criteria: January 24, 2018
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: SYM2014-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: Yes