Nasolabial Fold Correction
Conditions
Brief summary
A Multicenter, Double-Blind, Randomized, Split-Face Study to Evaluate the Safety and Efficacy of Revanesse® Ultra + (with Lidocaine) versus Revanesse® Ultra for the Correction of Nasolabial Folds to compare the safety and efficacy profiles of Revanesse® Ultra + (with lidocaine, hereafter referred to as Revanesse Ultra +) to Revanesse Ultra for subjects undergoing correction of nasolabial folds (NLFs)
Detailed description
This is a randomized, multicenter, double-blind, split-face study in subjects seeking nasolabial fold correction. Subjects will be treated with Revanesse Ultra + in the NLF on one side of the face and Revanesse Ultra in the NLF on the other side of the face. The side of the face for each study product will be randomly assigned. The investigator and the subject will be blinded to the treatment; injections of the study product will be performed by an unblinded injecting investigator. At each visit, investigator and subject evaluations of the treated areas will be performed and recorded
Interventions
DEVICERevanesse Ultra+ (with lidocaine)
Bilateral nasolabial fold trial to compare the safety and efficacy profiles of Revanesse® Ultra + (with lidocaine) to Revanesse® Ultra (comparator)
DEVICERevanesse Ultra
Comparator without lidocaine
Sponsors
Prollenium Medical Technologies Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
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.
Intervention model description
Subjects were treated with Revanesse Ultra in the NLF on one side of the face and Revanesse Ultra+ in the NLF on the other side of the face. The side of the face for each study product was randomly assigned.
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 seeking augmentation therapy for correction of bilateral nasolabial folds. 2. Two fully visible bilateral nasolabial folds each with a Wrinkle Severity Rating Scale Score (WSRS) of 3 or 4 that may be corrected with an injectable dermal filler. The NLFs should be symmetrical, i.e., WSRS scores at NLFs on both sides should be the same (both Moderate \[3\] or both Severe \[4\]). 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, or had undergone procedures based on active dermal response (e.g., laser or chemical peeling procedures) within 6 months (180 days) prior to study entry. 4. Use of any facial tissue augmenting therapy with non-permanent filler or aesthetic facial surgical therapy within 9 months prior to study entry. 5. Has ever received semi-permanent fillers anywhere in the face or neck, or is planning to be implanted with these products during the study. 6. Has a permanent implant placed in the NLF area. 7. Evidence of scar-related disease or delayed healing activity within the past 1 year. 8. Scars at the intended treatment sites. 9. History of keloid formation or hypertrophic scars. 10. Any infection or unhealed wound on the face. 11. Allergic history including anaphylaxis, multiple severe allergies, atopy, or allergies to natural rubber latex, lidocaine or any amide-based anesthetic, hyaluronic acid products, or Streptococcal proteins or have plans to undergo desensitization therapy during the term of the study. 12. Aspirin or nonsteroidal anti-inflammatory drugs within 1 week (7 days) prior to treatment. 13. Concomitant anticoagulant therapy, antiplatelet therapy, or history of bleeding disorders, coagulation defects or connective tissue disorders. 14. Over-the-counter (OTC) wrinkle products or prescription wrinkle treatments within 4 weeks (28 days) prior to treatment and throughout the study. 15. Immunocompromised or immunosuppressed. 16. 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. 17. Received any investigational product within 30 days of signing the Informed Consent Form. 18. Facial tattoo that may interfere with diagnosis. 19. 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. 20. Acne and/or other inflammatory diseases of the skin. 21. Acute or chronic skin disease, inflammation or related conditions, cancerous or precancerous lesions on or near the injection sites.-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain at Injection as Measured by Subject on a 100 mm Visual Analog Scale (VAS) Scale at Time 0 Minutes Post Injection | at injection Time 0 | Visual Analog Scale for Pain. A 100 mm scale with 0 mm being no pain (best outcome) to 100 mm being worst pain (worst outcome). The higher scores mean a worse outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Measured by Subject on 100 mm VAS Scale at 15, 30, 45, and 60 Minutes Post Injection and at 2 Weeks Post Injection | 15, 30, 45, and 60 minutes post injection and at 2 weeks post injection | Visual Analog Scale for pain. A 100 mm scale with 0 mm being no pain (best outcome) to 100 mm being worst pain (worst outcome). The higher score means a worse outcome. |
| Wrinkle Severity Rating Score (WSRS) | Visit 2/Day 14 (± 2 days), Visit 3/Day 28 (± 2 days), Visit 4/Day 84 (± 4 days), Visit 5/Day 168 (Week 24) (± 7 days) | The Wrinkle Severity Rating Scale is a 5-point scale with 1 = Absent; 2 = Mild; 3 = Moderate; 4 = Severe and 5 = Extreme. 1 is the best outcome while 5 is the worst outcome. The higher scores mean a worse outcome. |
| Patient Global Aesthetic Improvement | Visit 2/Day 14 (± 2 days), Visit 3/Day 28 (± 2 days), Visit 4/Day 84 (± 4 days), Visit 5/Day 168 (Week 24) (± 7 days) | Patient Global Aesthetic Improvement Score is a 5-point scale used to assess the subject's satisfaction with the visual appearance of their NLF correction after treatment. 1 = Worse (worst outcome), 2 = No Change, 3 = Improved, 4 = Much Improved, 5 = Very Much improved (best outcome). The higher scores mean a better outcome. |
| Investigator Global Aesthetic Improvement | Visit 2/Day 14 (± 2 days), Visit 3/Day 28 (± 2 days), Visit 4/Day 84 (± 4 days), Visit 5/Day 168 (Week 24) (± 7 days) | Investigator Global Aesthetic Improvement Score is a 5-point scale with 1 = Worse (worst outcome); 2 = No Change; 3 = Improved; 4 = Much Improved, 5 = Very much improved (best outcome). The higher scores mean a better outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Revanesse Ultra and Revanesse Ultra+ Injection by Incidence of Treatment Emergent Adverse Events | at injection, Visit 2/Day 14 (± 2 days), Visit 3/Day 28 (± 2 days), Visit 4/Day 84 (± 4 days), Visit 5/Day 168 (Week 24) (± 7 days) | study products will be compared by evaluating the nature, severity, and frequency of treatment-emergent adverse events (TEAEs) |
Countries
United States
Participant flow
Recruitment details
The study was undertaken between August 24 2016 and June 21 2017. Subjects that were randomized, there were 100 intent-to-treat (ITT), 95 modified intent-to-treat (mITT), 75 per-protocol (PP) subjects. Of the subjects randomized there were 17 subjects in the rollover subset (17 ITT, 12 mITT, and 12 PP subjects). 96 Subjects completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Revanesse Ultra+ Revanesse Ultra+ (with lidocaine)
Revanesse Ultra+ (with lidocaine): Bilateral nasolabial fold trial to compare the safety and efficacy profiles of Revanesse® Ultra + (with lidocaine) to Revanesse® Ultra (comparator)
Revanesse Ultra: Comparator without lidocaine | 100 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Revanesse Ultra+ |
|---|---|
| Age, Categorical <=18 years | NA Participants |
| Age, Categorical >=65 years | 21 Participants |
| Age, Categorical Between 18 and 65 years | 73 Participants |
| Age, Continuous | 58.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 89 Participants |
| Region of Enrollment United States | 100 participants |
| Sex: Female, Male Female | 93 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 / 100 | 0 / 100 |
| other Total, other adverse events | 53 / 100 | 52 / 100 |
| serious Total, serious adverse events | 0 / 100 | 1 / 100 |
Outcome results
Primary
Pain at Injection as Measured by Subject on a 100 mm Visual Analog Scale (VAS) Scale at Time 0 Minutes Post Injection
Visual Analog Scale for Pain. A 100 mm scale with 0 mm being no pain (best outcome) to 100 mm being worst pain (worst outcome). The higher scores mean a worse outcome
Time frame: at injection Time 0
Population: mITT: All randomized subjects who met the inclusion/exclusion criteria, were randomized, received both study products, and had VAS pain score immediately post injection from both sides of the face
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Revanesse Ultra+ | Pain at Injection as Measured by Subject on a 100 mm Visual Analog Scale (VAS) Scale at Time 0 Minutes Post Injection | 26.2 VAS | Standard Deviation 24.51 |
| Revanesse Ultra | Pain at Injection as Measured by Subject on a 100 mm Visual Analog Scale (VAS) Scale at Time 0 Minutes Post Injection | 39.4 VAS | Standard Deviation 25.45 |
Secondary
Investigator Global Aesthetic Improvement
Investigator Global Aesthetic Improvement Score is a 5-point scale with 1 = Worse (worst outcome); 2 = No Change; 3 = Improved; 4 = Much Improved, 5 = Very much improved (best outcome). The higher scores mean a better outcome.
Time frame: Visit 2/Day 14 (± 2 days), Visit 3/Day 28 (± 2 days), Visit 4/Day 84 (± 4 days), Visit 5/Day 168 (Week 24) (± 7 days)
Population: mITT: All randomized subjects who met the inclusion/exclusion criteria, were randomized, received both study products, and had VAS pain score immediately post injection from both sides of the face
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Revanesse Ultra+ | Investigator Global Aesthetic Improvement | Visit 2/Week 2 | 0.02 score on a scale | Standard Deviation 0.48 |
| Revanesse Ultra+ | Investigator Global Aesthetic Improvement | Visit 3/Week 4 | -0.02 score on a scale | Standard Deviation 0.14 |
| Revanesse Ultra+ | Investigator Global Aesthetic Improvement | Visit 4/Week 12 | -0.01 score on a scale | Standard Deviation 0.18 |
| Revanesse Ultra+ | Investigator Global Aesthetic Improvement | Visit 5/Week 24 | 0.03 score on a scale | Standard Deviation 0.17 |
Secondary
Pain Measured by Subject on 100 mm VAS Scale at 15, 30, 45, and 60 Minutes Post Injection and at 2 Weeks Post Injection
Visual Analog Scale for pain. A 100 mm scale with 0 mm being no pain (best outcome) to 100 mm being worst pain (worst outcome). The higher score means a worse outcome.
Time frame: 15, 30, 45, and 60 minutes post injection and at 2 weeks post injection
Population: mITT: All randomized subjects who met the inclusion/exclusion criteria, were randomized, received both study products, and had VAS pain score immediately post injection from both sides of the face
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Revanesse Ultra+ | Pain Measured by Subject on 100 mm VAS Scale at 15, 30, 45, and 60 Minutes Post Injection and at 2 Weeks Post Injection | 30 minutes post injection | 4.72 VAS score | Standard Deviation 9.1 |
| Revanesse Ultra+ | Pain Measured by Subject on 100 mm VAS Scale at 15, 30, 45, and 60 Minutes Post Injection and at 2 Weeks Post Injection | 60 minutes post injection | 2.13 VAS score | Standard Deviation 6.39 |
| Revanesse Ultra+ | Pain Measured by Subject on 100 mm VAS Scale at 15, 30, 45, and 60 Minutes Post Injection and at 2 Weeks Post Injection | 45 minutes post injection | 2.66 VAS score | Standard Deviation 6.61 |
| Revanesse Ultra+ | Pain Measured by Subject on 100 mm VAS Scale at 15, 30, 45, and 60 Minutes Post Injection and at 2 Weeks Post Injection | 2 weeks post injection | 0.25 VAS score | Standard Deviation 1.07 |
| Revanesse Ultra+ | Pain Measured by Subject on 100 mm VAS Scale at 15, 30, 45, and 60 Minutes Post Injection and at 2 Weeks Post Injection | 15 minutes post injection | 9.52 VAS score | Standard Deviation 14.83 |
| Revanesse Ultra | Pain Measured by Subject on 100 mm VAS Scale at 15, 30, 45, and 60 Minutes Post Injection and at 2 Weeks Post Injection | 2 weeks post injection | 0.25 VAS score | Standard Deviation 1.07 |
| Revanesse Ultra | Pain Measured by Subject on 100 mm VAS Scale at 15, 30, 45, and 60 Minutes Post Injection and at 2 Weeks Post Injection | 15 minutes post injection | 15.26 VAS score | Standard Deviation 18.37 |
| Revanesse Ultra | Pain Measured by Subject on 100 mm VAS Scale at 15, 30, 45, and 60 Minutes Post Injection and at 2 Weeks Post Injection | 30 minutes post injection | 7.46 VAS score | Standard Deviation 11.06 |
| Revanesse Ultra | Pain Measured by Subject on 100 mm VAS Scale at 15, 30, 45, and 60 Minutes Post Injection and at 2 Weeks Post Injection | 45 minutes post injection | 4.21 VAS score | Standard Deviation 7.89 |
| Revanesse Ultra | Pain Measured by Subject on 100 mm VAS Scale at 15, 30, 45, and 60 Minutes Post Injection and at 2 Weeks Post Injection | 60 minutes post injection | 2.86 VAS score | Standard Deviation 7.28 |
Secondary
Patient Global Aesthetic Improvement
Patient Global Aesthetic Improvement Score is a 5-point scale used to assess the subject's satisfaction with the visual appearance of their NLF correction after treatment. 1 = Worse (worst outcome), 2 = No Change, 3 = Improved, 4 = Much Improved, 5 = Very Much improved (best outcome). The higher scores mean a better outcome.
Time frame: Visit 2/Day 14 (± 2 days), Visit 3/Day 28 (± 2 days), Visit 4/Day 84 (± 4 days), Visit 5/Day 168 (Week 24) (± 7 days)
Population: mITT: All randomized subjects who met the inclusion/exclusion criteria, were randomized, received both study products, and had VAS pain score immediately post injection from both sides of the face.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Revanesse Ultra+ | Patient Global Aesthetic Improvement | Visit 2/Week 2 | 0.04 score on a scale | Standard Deviation 0.35 |
| Revanesse Ultra+ | Patient Global Aesthetic Improvement | Visit 3/Week 4 | -0.10 score on a scale | Standard Deviation 0.42 |
| Revanesse Ultra+ | Patient Global Aesthetic Improvement | Visit 4/Week 12 | -0.07 score on a scale | Standard Deviation 0.38 |
| Revanesse Ultra+ | Patient Global Aesthetic Improvement | Visit 5/Week 24 | 0.00 score on a scale | Standard Deviation 0.46 |
Secondary
Wrinkle Severity Rating Score (WSRS)
The Wrinkle Severity Rating Scale is a 5-point scale with 1 = Absent; 2 = Mild; 3 = Moderate; 4 = Severe and 5 = Extreme. 1 is the best outcome while 5 is the worst outcome. The higher scores mean a worse outcome.
Time frame: Visit 2/Day 14 (± 2 days), Visit 3/Day 28 (± 2 days), Visit 4/Day 84 (± 4 days), Visit 5/Day 168 (Week 24) (± 7 days)
Population: mITT: All randomized subjects who met the inclusion/exclusion criteria, were randomized, received both study products, and had VAS pain score immediately post injection from both sides of the face.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Revanesse Ultra+ | Wrinkle Severity Rating Score (WSRS) | Visit 2/Week 2 | -0.03 Wrinkle Severity Rating scale | Standard Deviation 0.402 |
| Revanesse Ultra+ | Wrinkle Severity Rating Score (WSRS) | Visit 3/ Week 4 | 0.02 Wrinkle Severity Rating scale | Standard Deviation 0.25 |
| Revanesse Ultra+ | Wrinkle Severity Rating Score (WSRS) | Visit 4/Week 12 | 0.00 Wrinkle Severity Rating scale | Standard Deviation 0.21 |
| Revanesse Ultra+ | Wrinkle Severity Rating Score (WSRS) | Visit 5/Week 24 | -0.02 Wrinkle Severity Rating scale | Standard Deviation 0.25 |
Other Pre-specified
Safety and Tolerability of Revanesse Ultra and Revanesse Ultra+ Injection by Incidence of Treatment Emergent Adverse Events
study products will be compared by evaluating the nature, severity, and frequency of treatment-emergent adverse events (TEAEs)
Time frame: at injection, Visit 2/Day 14 (± 2 days), Visit 3/Day 28 (± 2 days), Visit 4/Day 84 (± 4 days), Visit 5/Day 168 (Week 24) (± 7 days)
Population: ITT (safety population): All randomized subjects who received study product
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Revanesse Ultra+ | Safety and Tolerability of Revanesse Ultra and Revanesse Ultra+ Injection by Incidence of Treatment Emergent Adverse Events | 112 events |
| Revanesse Ultra | Safety and Tolerability of Revanesse Ultra and Revanesse Ultra+ Injection by Incidence of Treatment Emergent Adverse Events | 102 events |