Nasolabial Fold Correction
Conditions
Brief summary
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.
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.
Interventions
DEVICERevanesse Ultra
NLF correction
DEVICERestylane
NLF Correction
Sponsors
Prollenium Medical Technologies Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
Yes
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. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy Variable is Change From Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) Score | Visit 6/Week 24 | 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: 1. Absent - No visible fold; continuous skin line. 2. Mild - Shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance. 3. Moderate - Moderately deep folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected from injectable implant. 4. Severe - Very long and deep folds; prominent facial feature; less than 2 mm visible when stretched; significant improvement is expected from injectable implant. 5. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Efficacy Endpoints Are the Responder Rate, Percentage of *Nasolabial Folds* With Treatment Success | Visit 6/Week 24 | 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Other Efficacy Variables Include Change in WSRS Score | Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12 | Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24) |
| Other Efficacy Variables Include Change in Patient Global Aesthetic Improvement (pGAI) Score | Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12 | Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24) |
| Other Efficacy Variables Include Change in Investigator Global Aesthetic Improvement (iGAI) Score | Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12 | Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24) |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Split Face Study Bilateral Revanesse Ultra vs Restylane in NLF Split face study - Revanesse Ultra in the NLF on one side of the face and Restylane on the opposite side of the face for NLF correction, treatment is randomized | 163 |
| Split Face Study Bilateral Revanesse Ultra vs Restylane in NLF Split face study - Revanesse Ultra in the NLF on one side of the face and Restylane on the opposite side of the face for NLF correction, treatment is randomized | 326 |
| Total | 489 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Split Face Study Bilateral Revanesse Ultra vs Restylane in NLF |
|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 10.16 |
| Age, Customized 22 to <40 years | 15 Participants |
| Age, Customized 40 to <64 years | 110 Participants |
| Age, Customized 64 to <75 years | 35 Participants |
| Age, Customized = or >75 years | 3 Participants |
| Body Mass Index (BMI) | 26.27 kg/m^2 STANDARD_DEVIATION 5.374 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 146 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fitzpatrick Skin Type (FST) Classification FST I | 3 Participants |
| Fitzpatrick Skin Type (FST) Classification FST II | 50 Participants |
| Fitzpatrick Skin Type (FST) Classification FST III | 83 Participants |
| Fitzpatrick Skin Type (FST) Classification FST IV | 16 Participants |
| Fitzpatrick Skin Type (FST) Classification FST V | 4 Participants |
| Fitzpatrick Skin Type (FST) Classification FST VI | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 154 Participants |
| Sex: Female, Male Female | 156 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 163 | 0 / 163 |
| other Total, other adverse events | 114 / 163 | 137 / 163 |
| serious Total, serious adverse events | 0 / 163 | 1 / 163 |
Outcome results
Primary
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: 1. Absent - No visible fold; continuous skin line. 2. Mild - Shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance. 3. Moderate - Moderately deep folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected from injectable implant. 4. Severe - Very long and deep folds; prominent facial feature; less than 2 mm visible when stretched; significant improvement is expected from injectable implant. 5. 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.
Time frame: Visit 6/Week 24
Population: Analysis of effectiveness based on Per Protocol analysis which includes 125 evaluable patients at 24 weeks.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Revanesse Ultra | Primary Efficacy Variable is Change From Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) Score | 1.02 scores on a scale |
| Restylane | Primary Efficacy Variable is Change From Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) Score | 0.91 scores on a scale |
p-value: 0.013Wilcoxon (Mann-Whitney)
Secondary
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).
Time frame: Visit 6/Week 24
Population: Per-Protocol (PP) Population
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Revanesse Ultra | Secondary Efficacy Endpoints Are the Responder Rate, Percentage of *Nasolabial Folds* With Treatment Success | 98 Nasolabial Folds |
| Restylane | Secondary Efficacy Endpoints Are the Responder Rate, Percentage of *Nasolabial Folds* With Treatment Success | 91 Nasolabial Folds |
Other Pre-specified
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)
Time frame: Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12
Other Pre-specified
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)
Time frame: Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12
Other Pre-specified
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)
Time frame: Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12