Correction of Moderate to Severe Nasolabial Folds (NLFs)
Conditions
Brief summary
Effectiveness: The purpose of this study is to demonstrate the non-inferiority of Radiesse (CaHA) to Restylane (HA) following subdermal implantation for the correction of moderate to severe facial wrinkles and folds, such as NLFs. Safety: To evaluate the incidence and type of adverse events and serious adverse events.
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
* Has symmetrical NLFs, with the same WSRS score of 3 or 4 (moderate or severe) for both right and left NLFs, as determined on live assessment by the blinded evaluator. * Is ≥ 22 and ≤ 65 years of age. * Is willing to abstain from all other aesthetic treatments on any part of the face, including but not limited to injectable fillers, implants, neurotoxin, skin peels, laser treatments, surgical treatments, etc. for the trial's duration.
Exclusion criteria
* Has an acute inflammatory process or active infection at the injection site. * Has received mid- and/or lower-facial region treatments with any dermal fillers. * Has received facial dermal therapies. * Had prior surgery in the mid- and/or lower-facial area, including the NLFs, or has a permanent implant or graft in the mid- and/or lowerfacial area that could interfere with effectiveness assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 on the Wrinkle Severity Rating Scale (WSRS) | Baseline and Week 24 after last injection, up to 28 weeks | Severity of the nasolabial folds (NLFs) was assessed and measured using the 5-point Wrinkle Severity Rating Scale (WSRS), where 1=absent and 5=extreme. A lower score indicates better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Improvement on the Investigator Global Aesthetic Improvement Scale (iGAIS) for Each Nasolabial Fold (NLF) at Week 24 | Week 24 after last injection, up to 28 weeks | The Investigator Global Aesthetic Improvement Scale is a subjective assessment where the treating physician describes the degree of improvement in facial appearance ranging from Very much improved (+3) to Very much worse (-3). The investigator was asked to rate each NLF separately and select the rating that best applied when asked What is the overall impression of aesthetic change of the subject's NLF due to treatment, compared to the pretreatment photograph. Improvement was defined as a rating of +1, +2, or +3. The higher the iGAIS score, the greater the improvement. Proportion refers to percentage of participants. |
| Proportion of Subjects With Any Improvement on the Subject Global Aesthetic Improvement Scale (sGAIS) for Each Nasolabial Fold (NLF) at Week 24 | Week 24 after last injection, up to 28 weeks | The Subject Global Aesthetic Improvement Scale is a subjective self-assessment where the subject independently describes the degree of improvement in facial appearance ranging from Very much improved (+3) to Very much worse (-3). Subjects rated each NLF separately when asked What is the overall impression of aesthetic change of your NLF due to treatment, compared to the pretreatment photograph? Improvement is defined as a rating of +1, +2, or +3. The higher the sGAIS score, the greater the improvement. Proportion refers to percentage of participants. |
| Number of Subjects With Treatment-emergent Adverse Events (AE) Related to Radiesse | Baseline to week 48 after last injection, up to 52 weeks | Defined as AEs with onset at or after date of first administration of Radiesse. An AE was considered to be related if a causal relationship between Radiesse or the treatment procedure and the AE is at least reasonably possible. |
Countries
China
Participant flow
Recruitment details
Subjects were recruited from 7 investigational sites in China.
Pre-assignment details
Of the 134 enrolled, 13 subjects were exited as screen failures. This reporting group includes all randomized subjects (121).
Participants by arm
| Arm | Count |
|---|---|
| Radiesse and Restylane Subjects were randomized to receive Radiesse in either of the two nasolabial folds and Restylane in the respective other. | 120 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Radiesse and Restylane |
|---|---|
| Age, Continuous | 46.6 years STANDARD_DEVIATION 9.41 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 120 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 0 Participants |
| Sex: Female, Male Female | 107 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 120 | 0 / 120 | 0 / 120 |
| other Total, other adverse events | 7 / 120 | 18 / 120 | 9 / 120 |
| serious Total, serious adverse events | 0 / 120 | 0 / 120 | 7 / 120 |
Outcome results
Primary
Change From Baseline to Week 24 on the Wrinkle Severity Rating Scale (WSRS)
Severity of the nasolabial folds (NLFs) was assessed and measured using the 5-point Wrinkle Severity Rating Scale (WSRS), where 1=absent and 5=extreme. A lower score indicates better outcome.
Time frame: Baseline and Week 24 after last injection, up to 28 weeks
Population: This analysis population includes all randomized and treated subjects with no major protocol deviations or other events that impact analysis of the primary effectiveness endpoint (Per Protocol Set) with observed cases at the Week 24 visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Restylane | Change From Baseline to Week 24 on the Wrinkle Severity Rating Scale (WSRS) | Baseline | 3.4 score on a scale | Standard Deviation 0.5 |
| Restylane | Change From Baseline to Week 24 on the Wrinkle Severity Rating Scale (WSRS) | Week 24 | 2.4 score on a scale | Standard Deviation 0.62 |
| Radiesse | Change From Baseline to Week 24 on the Wrinkle Severity Rating Scale (WSRS) | Baseline | 3.4 score on a scale | Standard Deviation 0.5 |
| Radiesse | Change From Baseline to Week 24 on the Wrinkle Severity Rating Scale (WSRS) | Week 24 | 2.4 score on a scale | Standard Deviation 0.7 |
95% CI: [-0.07, 0.12]
Secondary
Number of Subjects With Treatment-emergent Adverse Events (AE) Related to Radiesse
Defined as AEs with onset at or after date of first administration of Radiesse. An AE was considered to be related if a causal relationship between Radiesse or the treatment procedure and the AE is at least reasonably possible.
Time frame: Baseline to week 48 after last injection, up to 52 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Restylane | Number of Subjects With Treatment-emergent Adverse Events (AE) Related to Radiesse | 23 Participants |
Secondary
Proportion of Subjects With Any Improvement on the Subject Global Aesthetic Improvement Scale (sGAIS) for Each Nasolabial Fold (NLF) at Week 24
The Subject Global Aesthetic Improvement Scale is a subjective self-assessment where the subject independently describes the degree of improvement in facial appearance ranging from Very much improved (+3) to Very much worse (-3). Subjects rated each NLF separately when asked What is the overall impression of aesthetic change of your NLF due to treatment, compared to the pretreatment photograph? Improvement is defined as a rating of +1, +2, or +3. The higher the sGAIS score, the greater the improvement. Proportion refers to percentage of participants.
Time frame: Week 24 after last injection, up to 28 weeks
Population: Subjects in the Per Protocol Set with observed cases at the Week 24 visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Restylane | Proportion of Subjects With Any Improvement on the Subject Global Aesthetic Improvement Scale (sGAIS) for Each Nasolabial Fold (NLF) at Week 24 | 80.70 percentage of participants |
| Radiesse | Proportion of Subjects With Any Improvement on the Subject Global Aesthetic Improvement Scale (sGAIS) for Each Nasolabial Fold (NLF) at Week 24 | 82.46 percentage of participants |
95% CI: [-3.08, 6.74]
Secondary
Proportion of Subjects With Improvement on the Investigator Global Aesthetic Improvement Scale (iGAIS) for Each Nasolabial Fold (NLF) at Week 24
The Investigator Global Aesthetic Improvement Scale is a subjective assessment where the treating physician describes the degree of improvement in facial appearance ranging from Very much improved (+3) to Very much worse (-3). The investigator was asked to rate each NLF separately and select the rating that best applied when asked What is the overall impression of aesthetic change of the subject's NLF due to treatment, compared to the pretreatment photograph. Improvement was defined as a rating of +1, +2, or +3. The higher the iGAIS score, the greater the improvement. Proportion refers to percentage of participants.
Time frame: Week 24 after last injection, up to 28 weeks
Population: Subjects in the Per Protocol Set with observed cases at the Week 24 visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Restylane | Proportion of Subjects With Improvement on the Investigator Global Aesthetic Improvement Scale (iGAIS) for Each Nasolabial Fold (NLF) at Week 24 | 77.19 percentage of participants |
| Radiesse | Proportion of Subjects With Improvement on the Investigator Global Aesthetic Improvement Scale (iGAIS) for Each Nasolabial Fold (NLF) at Week 24 | 77.19 percentage of participants |
95% CI: [-6.35, 6.35]