Nasolabial Fold Correction
Conditions
Brief summary
To compare improvement with retreatment for all subjects undergoing correction of nasolabial folds (NLFs) in the initial SYM2014-02 study, who were retreated with Revanesse Ultra at Visit 6/Week 24 and to determine the safety of repeat injections of Revanesse Ultra. The retreatment phase was optional.
Detailed description
The subjects completing the initial phase of the SYM2014-02 study (NCT02987205) who had returned to baseline Wrinkle Severity Rating Scale (WSRS) score or as needed for optimal correction if WSRS scores had not returned to baseline, were offered the option for retreatment with Revanesse Ultra Visit 6/Week 24 (± 7 days) optional open-label retreatment with Revanesse Ultra for subjects who had returned to baseline Wrinkle Severity Rating Scale (WSRS) score or as needed for optimal correction if WSRS scores had not returned to baseline; End of Study for subjects not being retreated Visit 7/Week 28 (± 7 days) follow-up for retreated subjects Visit 8/Week 52 (± 7 days) End of Study for retreated subjects A telephone contact was performed at Week 40 (± 7 days) for retreated subjects to assess adverse events (AEs) and concomitant medications. This report presents the results for all subjects who received optional open-label retreatment with Revanesse Ultra at Visit 6/Week 24. This study was performed in compliance with Good Clinical Practice (GCP), including the archiving of essential documents. Number of Subjects (Planned and Analyzed): Seventy-one subjects received retreatment.
Interventions
DEVICERevanesse Ultra
Nasolabial Fold correction
Sponsors
Prollenium Medical Technologies Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Subjects from the SYM2014-02 initial study who were: * Men or women at least 22 years of age with two fully visible bilateral nasolabial folds each with a WSRS score of 3 or 4 (moderate or severe) that may have been corrected with an injectable dermal filler. * Subjects were eligible for retreatment when WSRS scores had returned to baseline for either or both NLFs (retreatment group). * If scores had not returned to baseline, subjects were also eligible to be injected for either one or both NLFs as needed to achieve optimal correction (optimal correction group).
Exclusion criteria
\-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups - WSRS Scores at Visit 8/Week 52 | Visit 8/Week 52 | Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups Achieving Similar WSRS Scores at Visit 8/Week 52 - 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. An increase in the WSRS score indicates a worsening of severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Visit 6/Week 24, Visit 7/Week 28, Visit 8/Week 52 | Assess safety concerns with retreatment of Revanesse Ultra for men or women at least 22 years of age with NLFs with a moderate or severe WSRS score at baseline who had previously received 1 or 2 treatments with Restylane or Revanesse Ultra, Adverse Events (AEs), which were defined, recorded, reported, and evaluated |
| Patient Global Aesthetic Improvement (pGAI) Score | Visit 8/Week 52 | Subjects were evaluated on the Patient Global Aesthetic Improvement (pGAI) Patient Global Aesthetic Improvement (pGAI) Score: 1 = Worse, 2 = No change, 3 = Improved, 4 = Much improved, 5 = Very much improved |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Revanesse Ultra Retreatment Revanesse Ultra open label retreatment / Nasolabial Fold correction - optional open-label retreatment with Revanesse Ultra for subjects who had returned to baseline Wrinkle Severity Rating Scale (WSRS) score The subjects completing the initial phase of the SYM2014-02 study (NCT02987205) who had returned to baseline Wrinkle Severity Rating Scale (WSRS) score, were offered the option for retreatment with Revanesse Ultra Safety data was collected to assess treatment emergent adverse events associated with repeat injections. Seventy-one subjects received retreatment - 30 returned to baseline | 30 |
| Revanesse Ultra Optimal Correction Revanesse Ultra open label retreatment / Nasolabial Fold correction - optional open-label retreatment with Revanesse Ultra for subjects as needed for optimal correction if WSRS scores had not returned to baseline.
The subjects completing the initial phase of the SYM2014-02 study (NCT02987205) were treated as needed for optimal correction if WSRS scores had not returned to baseline, and were offered the option for retreatment with Revanesse Ultra Safety data was collected to assess treatment emergent adverse events associated with repeat injections. Seventy-one subjects received retreatment - 41 were included in the optimal correction group | 41 |
| Total | 71 |
Baseline characteristics
| Characteristic | Revanesse Ultra Retreatment | Revanesse Ultra Optimal Correction | Total |
|---|---|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 9.19 | 54.5 years STANDARD_DEVIATION 10.44 | 56.1 years STANDARD_DEVIATION 10.05 |
| Age, Customized 22 to <40 years | 1 Participants | 5 Participants | 6 Participants |
| Age, Customized 40 to <64 years | 21 Participants | 27 Participants | 48 Participants |
| Age, Customized 64 to <75 years | 6 Participants | 9 Participants | 15 Participants |
| Age, Customized > = 75 years | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 8 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 33 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fitzpatrick Skin Type (FST) Classification FST I | 0 Participants | 0 Participants | 0 Participants |
| Fitzpatrick Skin Type (FST) Classification FST II | 10 Participants | 17 Participants | 27 Participants |
| Fitzpatrick Skin Type (FST) Classification FST III | 15 Participants | 15 Participants | 30 Participants |
| Fitzpatrick Skin Type (FST) Classification FST IV | 3 Participants | 3 Participants | 6 Participants |
| Fitzpatrick Skin Type (FST) Classification FST V | 1 Participants | 2 Participants | 3 Participants |
| Fitzpatrick Skin Type (FST) Classification FST VI | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 37 Participants | 66 Participants |
| Region of Enrollment United States | 30 Participants | 41 Participants | 71 Participants |
| Sex: Female, Male Female | 29 Participants | 37 Participants | 66 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 41 |
| other Total, other adverse events | 16 / 30 | 29 / 41 |
| serious Total, serious adverse events | 0 / 30 | 0 / 41 |
Outcome results
Primary
Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups - WSRS Scores at Visit 8/Week 52
Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups Achieving Similar WSRS Scores at Visit 8/Week 52 - 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. An increase in the WSRS score indicates a worsening of severity.
Time frame: Visit 8/Week 52
Population: Subjects that completed the SYM 2014-02 Main Study were eligible for the SYM 2014-02 Retreatment Study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Optimal Correction Group | Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups - WSRS Scores at Visit 8/Week 52 | Change in Main Study Treatment - Revanesse Ultra | 0.1 units on WSRS scale | Standard Deviation 0.69 |
| Optimal Correction Group | Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups - WSRS Scores at Visit 8/Week 52 | Change in Main Study Treatment - Restylane | 0.0 units on WSRS scale | Standard Deviation 0.69 |
| Retreatment Group | Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups - WSRS Scores at Visit 8/Week 52 | Change in Main Study Treatment - Revanesse Ultra | 0.6 units on WSRS scale | Standard Deviation 0.72 |
| Retreatment Group | Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups - WSRS Scores at Visit 8/Week 52 | Change in Main Study Treatment - Restylane | 0.8 units on WSRS scale | Standard Deviation 0.63 |
Secondary
Patient Global Aesthetic Improvement (pGAI) Score
Subjects were evaluated on the Patient Global Aesthetic Improvement (pGAI) Patient Global Aesthetic Improvement (pGAI) Score: 1 = Worse, 2 = No change, 3 = Improved, 4 = Much improved, 5 = Very much improved
Time frame: Visit 8/Week 52
Population: Subjects were evaluated on the Patient Global Aesthetic Improvement (pGAI)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Optimal Correction Group | Patient Global Aesthetic Improvement (pGAI) Score | Visit 8 - week 52 pGAI = 3 Improved | 13 Participants |
| Optimal Correction Group | Patient Global Aesthetic Improvement (pGAI) Score | Visit 8 - week 52 pGAI = 4 much improved | 1 Participants |
| Optimal Correction Group | Patient Global Aesthetic Improvement (pGAI) Score | Visit 8 - week 52 pGAI = 2 no change | 8 Participants |
| Optimal Correction Group | Patient Global Aesthetic Improvement (pGAI) Score | Visit 8 - week 52 pGAI = 5 Very much improved | 7 Participants |
| Optimal Correction Group | Patient Global Aesthetic Improvement (pGAI) Score | Visit 8 - week 52 pGAI = 1 worse | 1 Participants |
| Retreatment Group | Patient Global Aesthetic Improvement (pGAI) Score | Visit 8 - week 52 pGAI = 5 Very much improved | 4 Participants |
| Retreatment Group | Patient Global Aesthetic Improvement (pGAI) Score | Visit 8 - week 52 pGAI = 1 worse | 1 Participants |
| Retreatment Group | Patient Global Aesthetic Improvement (pGAI) Score | Visit 8 - week 52 pGAI = 2 no change | 8 Participants |
| Retreatment Group | Patient Global Aesthetic Improvement (pGAI) Score | Visit 8 - week 52 pGAI = 4 much improved | 12 Participants |
| Retreatment Group | Patient Global Aesthetic Improvement (pGAI) Score | Visit 8 - week 52 pGAI = 3 Improved | 16 Participants |
Secondary
Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity
Assess safety concerns with retreatment of Revanesse Ultra for men or women at least 22 years of age with NLFs with a moderate or severe WSRS score at baseline who had previously received 1 or 2 treatments with Restylane or Revanesse Ultra, Adverse Events (AEs), which were defined, recorded, reported, and evaluated
Time frame: Visit 6/Week 24, Visit 7/Week 28, Visit 8/Week 52
Population: Counts reflect numbers of subjects reporting one or more injection site TEAE that map to the MedDRA (version 15.1) system organ class/preferred term. At each level of summarization (system organ class or preferred term), subjects reporting more than one injection site TEAE are counted only once.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Optimal Correction Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Eye disorder - ocular hyperaemia | 0 Participants |
| Optimal Correction Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Gastrointestinal - mouth cyst | 0 Participants |
| Optimal Correction Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Injection site erythema | 2 Participants |
| Optimal Correction Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Injection site haematoma | 9 Participants |
| Optimal Correction Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Injection site mass | 1 Participants |
| Optimal Correction Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Injection site pain | 9 Participants |
| Optimal Correction Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Injection site pruritis | 0 Participants |
| Optimal Correction Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Injection site swelling | 0 Participants |
| Optimal Correction Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Contusion | 0 Participants |
| Optimal Correction Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Excoriation | 0 Participants |
| Retreatment Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Injection site swelling | 1 Participants |
| Retreatment Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Eye disorder - ocular hyperaemia | 1 Participants |
| Retreatment Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Injection site pain | 6 Participants |
| Retreatment Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Gastrointestinal - mouth cyst | 1 Participants |
| Retreatment Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Excoriation | 1 Participants |
| Retreatment Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Injection site erythema | 8 Participants |
| Retreatment Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Injection site pruritis | 1 Participants |
| Retreatment Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Injection site haematoma | 19 Participants |
| Retreatment Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Contusion | 1 Participants |
| Retreatment Group | Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity | Injection site mass | 2 Participants |