Trial Outcomes & Findings for Multicenter Study to Evaluate the Safety and Efficacy of Revanesse® Ultra Retreatment (NCT NCT02984878)

Last Updated: 2017-12-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

71 participants

Primary outcome timeframe

Visit 8/Week 52

Results posted on

2017-12-20

Participant Flow

Participant milestones

Participant milestones
Measure	Revanesse Ultra Retreatment Revanesse Ultra: Nasolabial Fold correction - - Subjects could have open-label retreatment as needed with Revanesse Ultra at 6 months if their WSRS scores had returned to baseline	Revanesse Ultra Optimal Correction The Optimal Correction group scores had not returned to baseline, subjects were eligible to be injected for either one or both NLFs as needed to achieve optimal correction (optimal correction group).
Overall Study STARTED	30	41
Overall Study COMPLETED	30	41
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Multicenter Study to Evaluate the Safety and Efficacy of Revanesse® Ultra Retreatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Revanesse Ultra Retreatment n=30 Participants 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	Revanesse Ultra Optimal Correction n=41 Participants 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	Total n=71 Participants Total of all reporting groups
Age, Continuous	58.3 years STANDARD_DEVIATION 9.19 • n=93 Participants	54.5 years STANDARD_DEVIATION 10.44 • n=4 Participants	56.1 years STANDARD_DEVIATION 10.05 • n=27 Participants
Age, Customized 22 to <40 years	1 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants
Age, Customized 40 to <64 years	21 Participants n=93 Participants	27 Participants n=4 Participants	48 Participants n=27 Participants
Age, Customized 64 to <75 years	6 Participants n=93 Participants	9 Participants n=4 Participants	15 Participants n=27 Participants
Age, Customized > = 75 years	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Sex: Female, Male Female	29 Participants n=93 Participants	37 Participants n=4 Participants	66 Participants n=27 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=93 Participants	8 Participants n=4 Participants	12 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=93 Participants	33 Participants n=4 Participants	59 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants
Race (NIH/OMB) White	29 Participants n=93 Participants	37 Participants n=4 Participants	66 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	30 Participants n=93 Participants	41 Participants n=4 Participants	71 Participants n=27 Participants
Fitzpatrick Skin Type (FST) Classification FST I	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Fitzpatrick Skin Type (FST) Classification FST II	10 Participants n=93 Participants	17 Participants n=4 Participants	27 Participants n=27 Participants
Fitzpatrick Skin Type (FST) Classification FST III	15 Participants n=93 Participants	15 Participants n=4 Participants	30 Participants n=27 Participants
Fitzpatrick Skin Type (FST) Classification FST IV	3 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants
Fitzpatrick Skin Type (FST) Classification FST V	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Fitzpatrick Skin Type (FST) Classification FST VI	1 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants

PRIMARY outcome

Timeframe: Visit 8/Week 52

Population: Subjects that completed the SYM 2014-02 Main Study were eligible for the SYM 2014-02 Retreatment Study.

Outcome measures

Outcome measures
Measure	Optimal Correction Group n=81 Nasolabial Folds Optional Open label Retreatment at Week 24 / SYM2014-02 Retreatment: At SYM 2014-02 Main Study Visit 6/Week 24, a subject could be retreated with Revanesse Ultra. Subjects were eligible for optimal correction when WSRS scores had not returned to baseline. Optimal Correction subjects were injected in either one or both NLFs as needed to achieve optimal correction. These subjects continued to day 196 (Visit 7 / week 28), received a phone contact at day 280 (week 40), and completed at day 364 (Visit 8 / week 52).	Retreatment Group n=60 Nasolabial Folds Revanesse Ultra open label retreatment for Nasolabial Fold correction. Optional Open-label Retreatment at Visit 6/Week 24 of the SYM 2014-02 Main Study, a subject could be retreated when WSRS scores had returned to baseline for either or both NLFs. The retreatment group and the optimal correction group were separated for data analysis. These subjects continued to day 196 (Visit 7 / week 28), received a phone contact at day 280 (week 40), and completed at day 364 (Visit 8 / week 52).
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	0.6 units on WSRS scale Standard Deviation 0.72
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	0.8 units on WSRS scale Standard Deviation 0.63

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Optimal Correction Group n=30 Participants Optional Open label Retreatment at Week 24 / SYM2014-02 Retreatment: At SYM 2014-02 Main Study Visit 6/Week 24, a subject could be retreated with Revanesse Ultra. Subjects were eligible for optimal correction when WSRS scores had not returned to baseline. Optimal Correction subjects were injected in either one or both NLFs as needed to achieve optimal correction. These subjects continued to day 196 (Visit 7 / week 28), received a phone contact at day 280 (week 40), and completed at day 364 (Visit 8 / week 52).	Retreatment Group n=41 Participants Revanesse Ultra open label retreatment for Nasolabial Fold correction. Optional Open-label Retreatment at Visit 6/Week 24 of the SYM 2014-02 Main Study, a subject could be retreated when WSRS scores had returned to baseline for either or both NLFs. The retreatment group and the optimal correction group were separated for data analysis. These subjects continued to day 196 (Visit 7 / week 28), received a phone contact at day 280 (week 40), and completed at day 364 (Visit 8 / week 52).
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	1 Participants
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	1 Participants
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	8 Participants
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	19 Participants
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	2 Participants
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	6 Participants
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	1 Participants
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	1 Participants
Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity Contusion	0 Participants	1 Participants
Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity Excoriation	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Visit 8/Week 52

Population: Subjects were evaluated on the Patient Global Aesthetic Improvement (pGAI)

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

Outcome measures

Outcome measures
Measure	Optimal Correction Group n=30 Participants Optional Open label Retreatment at Week 24 / SYM2014-02 Retreatment: At SYM 2014-02 Main Study Visit 6/Week 24, a subject could be retreated with Revanesse Ultra. Subjects were eligible for optimal correction when WSRS scores had not returned to baseline. Optimal Correction subjects were injected in either one or both NLFs as needed to achieve optimal correction. These subjects continued to day 196 (Visit 7 / week 28), received a phone contact at day 280 (week 40), and completed at day 364 (Visit 8 / week 52).	Retreatment Group n=41 Participants Revanesse Ultra open label retreatment for Nasolabial Fold correction. Optional Open-label Retreatment at Visit 6/Week 24 of the SYM 2014-02 Main Study, a subject could be retreated when WSRS scores had returned to baseline for either or both NLFs. The retreatment group and the optimal correction group were separated for data analysis. These subjects continued to day 196 (Visit 7 / week 28), received a phone contact at day 280 (week 40), and completed at day 364 (Visit 8 / week 52).
Patient Global Aesthetic Improvement (pGAI) Score Visit 8 - week 52 pGAI = 1 worse	1 Participants	1 Participants
Patient Global Aesthetic Improvement (pGAI) Score Visit 8 - week 52 pGAI = 2 no change	8 Participants	8 Participants
Patient Global Aesthetic Improvement (pGAI) Score Visit 8 - week 52 pGAI = 3 Improved	13 Participants	16 Participants
Patient Global Aesthetic Improvement (pGAI) Score Visit 8 - week 52 pGAI = 4 much improved	1 Participants	12 Participants
Patient Global Aesthetic Improvement (pGAI) Score Visit 8 - week 52 pGAI = 5 Very much improved	7 Participants	4 Participants

Adverse Events

Retreatment Group

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Optimal Correction Group

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Retreatment Group n=30 participants at risk Revanesse Ultra open label retreatment for Nasolabial Fold correction. Optional Open-label Retreatment at Visit 6/Week 24 of the SYM 2014-02 Main Study, a subject could be retreated when WSRS scores had returned to baseline for either or both NLFs. The retreatment group and the optimal correction group were separated for data analysis. These subjects continued to day 196 (Visit 7 / week 28), received a phone contact at day 280 (week 40), and completed at day 364 (Visit 8 / week 52).	Optimal Correction Group n=41 participants at risk Optional Open label Retreatment at Week 24 / SYM2014-02 Retreatment: At SYM 2014-02 Main Study Visit 6/Week 24, a subject could be retreated with Revanesse Ultra. Subjects were eligible for optimal correction when WSRS scores had not returned to baseline. Optimal Correction subjects were injected in either one or both NLFs as needed to achieve optimal correction. These subjects continued to day 196 (Visit 7 / week 28), received a phone contact at day 280 (week 40), and completed at day 364 (Visit 8 / week 52).
General disorders INJECTION SITE ERYTHEMA	6.7% 2/30 • Number of events 2 • Adverse Event data was collected at Retreatment for 6 months (Visit 8/Week 52 from the Main Study) Treatment safety was evaluated by frequency and percent of subjects and investigators reporting treatment-emergent adverse events (TEAEs) tabulated by treatment group, location, frequency, severity and duration after each treatment (initial treatment, touch up) and throughout the study. TEAEs were assessed by a subject diary after each injection, touch up and follow up visit, and were reported by the Evaluating Investigator at each of the follow-up visits.	22.0% 9/41 • Number of events 9 • Adverse Event data was collected at Retreatment for 6 months (Visit 8/Week 52 from the Main Study) Treatment safety was evaluated by frequency and percent of subjects and investigators reporting treatment-emergent adverse events (TEAEs) tabulated by treatment group, location, frequency, severity and duration after each treatment (initial treatment, touch up) and throughout the study. TEAEs were assessed by a subject diary after each injection, touch up and follow up visit, and were reported by the Evaluating Investigator at each of the follow-up visits.
General disorders INJECTION SITE HAEMATOMA	30.0% 9/30 • Number of events 9 • Adverse Event data was collected at Retreatment for 6 months (Visit 8/Week 52 from the Main Study) Treatment safety was evaluated by frequency and percent of subjects and investigators reporting treatment-emergent adverse events (TEAEs) tabulated by treatment group, location, frequency, severity and duration after each treatment (initial treatment, touch up) and throughout the study. TEAEs were assessed by a subject diary after each injection, touch up and follow up visit, and were reported by the Evaluating Investigator at each of the follow-up visits.	46.3% 19/41 • Number of events 19 • Adverse Event data was collected at Retreatment for 6 months (Visit 8/Week 52 from the Main Study) Treatment safety was evaluated by frequency and percent of subjects and investigators reporting treatment-emergent adverse events (TEAEs) tabulated by treatment group, location, frequency, severity and duration after each treatment (initial treatment, touch up) and throughout the study. TEAEs were assessed by a subject diary after each injection, touch up and follow up visit, and were reported by the Evaluating Investigator at each of the follow-up visits.
General disorders INJECTION SITE PAIN	30.0% 9/30 • Number of events 9 • Adverse Event data was collected at Retreatment for 6 months (Visit 8/Week 52 from the Main Study) Treatment safety was evaluated by frequency and percent of subjects and investigators reporting treatment-emergent adverse events (TEAEs) tabulated by treatment group, location, frequency, severity and duration after each treatment (initial treatment, touch up) and throughout the study. TEAEs were assessed by a subject diary after each injection, touch up and follow up visit, and were reported by the Evaluating Investigator at each of the follow-up visits.	14.6% 6/41 • Number of events 6 • Adverse Event data was collected at Retreatment for 6 months (Visit 8/Week 52 from the Main Study) Treatment safety was evaluated by frequency and percent of subjects and investigators reporting treatment-emergent adverse events (TEAEs) tabulated by treatment group, location, frequency, severity and duration after each treatment (initial treatment, touch up) and throughout the study. TEAEs were assessed by a subject diary after each injection, touch up and follow up visit, and were reported by the Evaluating Investigator at each of the follow-up visits.
General disorders INJECTION SITE SWELLING	30.0% 9/30 • Number of events 9 • Adverse Event data was collected at Retreatment for 6 months (Visit 8/Week 52 from the Main Study) Treatment safety was evaluated by frequency and percent of subjects and investigators reporting treatment-emergent adverse events (TEAEs) tabulated by treatment group, location, frequency, severity and duration after each treatment (initial treatment, touch up) and throughout the study. TEAEs were assessed by a subject diary after each injection, touch up and follow up visit, and were reported by the Evaluating Investigator at each of the follow-up visits.	34.1% 14/41 • Number of events 14 • Adverse Event data was collected at Retreatment for 6 months (Visit 8/Week 52 from the Main Study) Treatment safety was evaluated by frequency and percent of subjects and investigators reporting treatment-emergent adverse events (TEAEs) tabulated by treatment group, location, frequency, severity and duration after each treatment (initial treatment, touch up) and throughout the study. TEAEs were assessed by a subject diary after each injection, touch up and follow up visit, and were reported by the Evaluating Investigator at each of the follow-up visits.

Additional Information

Ario Khoshbin, President

Prollenium Medical Technologies, Inc.

Phone: 866-353-3015

Results disclosure agreements

Principal investigator is a sponsor employee There are restrictions within the site contracts, sites cannot publish any results and also have confidentiality agreements in place separately that restrict any publications by sites regarding results, findings, etc.
Publication restrictions are in place

Restriction type: OTHER