Correction of the Moderate to Severe Nasolabial Folds
Conditions
Brief summary
The objectives of this study are to evaluate the effectiveness and safety of Radiesse for the correction of nasolabial folds (NLFs).
Interventions
Subdermal injection.
Subdermal injection
Sponsors
Merz North America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Split-face
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Is 22 - 65 years of age. 2. Has symmetrical NLFs of moderate or severe intensity (grade 3 or 4) on the WSRS as determined by the independent blinded evaluator and confirmed by the treating investigator at baseline. 3. Both folds must have the same NLF score at baseline. 4. Has signed an informed consent. 5\. Understands and accepts the obligation not to receive any other facial procedures below the eyes during the study. 6\. Understands and accepts the obligation to present for all scheduled follow-up visits and is logistically able to meet all study requirements. 7\. Subjects of childbearing potential must have a negative pregnancy test result and must not be lactating at the Screening/Baseline Visit and be willing and able to use an acceptable method of birth control (e.g. barrier methods used with a spermicidal agent, hormonal methods, IUD, surgical sterilization, abstinence) during the study. Women will be considered if one of the following conditions is documented on the medical history: 1. Postmenopausal with last menstrual bleeding at least 12 months prior to study; and 2. Without a uterus and/or both ovaries.
Exclusion criteria
1. Has received surgical permanent implants, grafting, or surgery below the eyes on the face prior to injection or lower lid blepharoplasty within 6 months prior to injection. 2. Has received within the specified (washout) period or plans to receive treatment during the study conduct with a non-permanent facial filler in any facial area below the eyes: 1. 12 months prior to study start - hyaluronic acid \[HA\] or collagen 2. 18 months prior to study start - calcium hydroxylapatite \[CaHA\] 3. Has received at any time or plans to receive during the study a permanent facial filler (e.g. poly L-lactic acid \[PLLA\], polymethyl-methacrylate \[PMMA\], silicone) below the eyes. 4. Has received within the past 6 months or plans to receive during the study facial dermal resurfacing procedures (e.g. chemical peel, dermabrasion, ablative laser resurfacing), non-invasive skin-tightening (e.g. Thermage), botulinum toxin injections, mesotherapy, or fat injections below the eyes. 5. Has received in the past 2 weeks or plans to receive during the study any prescription wrinkle therapies (e.g. RENOVAÒ), topical steroids, skin irritating topical preparations, or pigmenting agents (self-tanning agents) for use on the face. 6. Has received in the past 2 months, or plans to receive immunosuppressive medications or systemic steroids (intranasal/inhaled steroids acceptable) during the study. 7. Has an acute inflammatory process or infection, active herpes infection, or history of chronic or recurrent infection or inflammation with the potential to interfere with the study results or increase the risk of adverse events (AEs). 8. Has a known bleeding disorder or has received or is planning to receive anti-coagulation, anti-platelet, or thrombolytic medications (e.g., warfarin), anti-inflammatory drugs (oral/injectable corticosteroids or NSAIDs (e.g., aspirin, ibuprofen), or other substances known to increase coagulation time (vitamins or herbal supplements, e.g., Vitamin E, garlic, gingko), from 10 days before injection to 3 days after injection. 9. Has a history of known liver or renal function disease/disorder or has clinically significant laboratory values at baseline. 10. Has a known history of allergic/anaphylactic reactions, including hypersensitivity to lidocaine or anesthetics of the amide type, or any of the device components. 11. Has a history of hyper- or hypo-pigmentation in the NLFs, keloid formation, or hypertrophic scarring. 12. Has recently lost or has the intention to lose a significant amount of weight ≥ 2 Body Mass Index (BMI) units during the course of the study. 13. Has any other medical condition with the potential to interfere with the study's conduct or assessments, or increase the risk of AEs. 14. Has participated in a study in the last 30 days or is enrolled or plans to enroll in any other interfering investigational study during participation in the study. 15. Is an employee or direct relative of an employee of the investigational department in site or the sponsor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of NLFs With Treatment Success at Month 6 | Month 6 | Treatment success was defined as a greater than or equal to (\>=) 1-point improvement from baseline, as assessed by a blinded evaluator wrinkle severity rating scale (WSRS) scale. WSRS is a 5 point scale with scores as Score 1: Absent; Score 2: Mild; Score 3: Moderate; Score 4: Severe; Score 5: Extreme. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of NLFs With an Improvement in the Blinded Evaluator's GAIS Score at Month 6 | Month 6 | The blinded evaluator rated the current cosmetic result for each NLF according to the GAIS based on live assessments during the visit compared with photographs taken at baseline before administration of treatment on each NLF. An improvement on the GAIS was classified as improved, much improved, or very much improved. The GAIS is a 7-point scale, where: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), and -3 (very much worse). |
Countries
China
Participant flow
Recruitment details
The study was conducted at 4 investigative sites in China.
Pre-assignment details
A total of 195 participants were screened, out of which 181 were randomized. Of these, 176 participants were treated and 164 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Radiesse and Restylane Participants received split-face NLF treatment with study product Radiesse, subdermal injection, in one of the two NLFs and control product Restylane, subdermal injection, in the contralateral NLF on Day 1. Participants received an optional touch-up injection in one or both the NLFs at Month 1. | 176 |
| Total | 176 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Other | 9 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Radiesse and Restylane |
|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 9.43 |
| Body Mass Index (BMI) | 21.87 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.817 |
| Fitzpatrick skin type Missing | 0 Participants |
| Fitzpatrick skin type Type I | 0 Participants |
| Fitzpatrick skin type Type II | 0 Participants |
| Fitzpatrick skin type Type III | 147 Participants |
| Fitzpatrick skin type Type IV | 29 Participants |
| Fitzpatrick skin type Type V | 0 Participants |
| Fitzpatrick skin type Type VI | 0 Participants |
| Height | 159.9 centimeter (cm) STANDARD_DEVIATION 5.6 |
| Race/Ethnicity, Customized Ethnicity Han Chinese | 173 Participants |
| Race/Ethnicity, Customized Ethnicity Other | 3 Participants |
| Race/Ethnicity, Customized Race (Asian) | 176 Participants |
| Region of Enrollment China | 176 Participants |
| Sex: Female, Male Female | 170 Participants |
| Sex: Female, Male Male | 6 Participants |
| Weight | 56.15 kilogram (Kg) STANDARD_DEVIATION 8.434 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 176 |
| other Total, other adverse events | 56 / 176 |
| serious Total, serious adverse events | 4 / 176 |
Outcome results
Primary
Percentage of NLFs With Treatment Success at Month 6
Treatment success was defined as a greater than or equal to (\>=) 1-point improvement from baseline, as assessed by a blinded evaluator wrinkle severity rating scale (WSRS) scale. WSRS is a 5 point scale with scores as Score 1: Absent; Score 2: Mild; Score 3: Moderate; Score 4: Severe; Score 5: Extreme.
Time frame: Month 6
Population: The per protocol set (PPS) was the subset of the full analysis set (FAS) without any major protocol deviations. The FAS was all participants randomized who received an investigational product with at least one post-baseline effectiveness assessment (WSRS, blind evaluator's Global Aesthetic Improvement Scale \[GAIS\] or participant's GAIS assessment).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiesse | Percentage of NLFs With Treatment Success at Month 6 | 66.0 Percentage of successfully treated NFLs |
| Restylane | Percentage of NLFs With Treatment Success at Month 6 | 72.8 Percentage of successfully treated NFLs |
95% CI: [-13.1, -0.5]
Secondary
Percentage of NLFs With an Improvement in the Blinded Evaluator's GAIS Score at Month 6
The blinded evaluator rated the current cosmetic result for each NLF according to the GAIS based on live assessments during the visit compared with photographs taken at baseline before administration of treatment on each NLF. An improvement on the GAIS was classified as improved, much improved, or very much improved. The GAIS is a 7-point scale, where: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), and -3 (very much worse).
Time frame: Month 6
Population: The PPS was defined as the subset of the FAS without any major protocol deviations. The FAS was defined as all participants randomized and who received an investigational product with at least one post-baseline effectiveness assessment (that is WSRS, blind evaluator's GAIS or participant's GAIS assessment).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiesse | Percentage of NLFs With an Improvement in the Blinded Evaluator's GAIS Score at Month 6 | 78.4 Percentage of NLFs |
| Restylane | Percentage of NLFs With an Improvement in the Blinded Evaluator's GAIS Score at Month 6 | 83.3 Percentage of NLFs |
95% CI: [-9.8, -0.3]