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

• ClinicalTrials.gov Identifier: NCT02984878
• Recruitment Status: Completed
• First Posted: December 7, 2016
• Results First Posted: December 20, 2017
• Last Update Posted: December 20, 2017
• Sponsor: Prollenium Medical Technologies Inc.
• Information provided by (Responsible Party): Prollenium Medical Technologies Inc.

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Nasolabial Fold Correction
• Intervention: Device: Revanesse Ultra
• Enrollment: 71

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Revanesse Ultra Retreatment	Revanesse Ultra Optimal Correction
Arm/Group Description	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	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).
Period Title: Overall Study
Started	30	41
Completed	30	41
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Revanesse Ultra Retreatment	Revanesse Ultra Optimal Correction	Total
Arm/Group Description		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 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 of all reporting groups
Overall Number of Baseline Participants		30	41	71
Baseline Analysis Population Description		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 or as needed for optimal correction if WSRS scores had not returned to baseline.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	30 participants	41 participants	71 participants
		58.3 (9.19)	54.5 (10.44)	56.1 (10.05)
Age, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	30 participants	41 participants	71 participants
22 to <40 years		1 3.3%	5 12.2%	6 8.5%
40 to <64 years		21 70.0%	27 65.9%	48 67.6%
64 to <75 years		6 20.0%	9 22.0%	15 21.1%
> = 75 years		2 6.7%	0 0.0%	2 2.8%
		[1] Measure Description: participants in each age group
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	41 participants	71 participants
	Female	29 96.7%	37 90.2%	66 93.0%
	Male	1 3.3%	4 9.8%	5 7.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	41 participants	71 participants
	Hispanic or Latino	4 13.3%	8 19.5%	12 16.9%
	Not Hispanic or Latino	26 86.7%	33 80.5%	59 83.1%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	41 participants	71 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 3.3%	4 9.8%	5 7.0%
	White	29 96.7%	37 90.2%	66 93.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	30 participants	41 participants	71 participants
		30 100.0%	41 100.0%	71 100.0%
Fitzpatrick Skin Type (FST) Classification [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	30 participants	41 participants	71 participants
FST I		0 0.0%	0 0.0%	0 0.0%
FST II		10 33.3%	17 41.5%	27 38.0%
FST III		15 50.0%	15 36.6%	30 42.3%
FST IV		3 10.0%	3 7.3%	6 8.5%
FST V		1 3.3%	2 4.9%	3 4.2%
FST VI		1 3.3%	4 9.8%	5 7.0%
		[1] Measure Description: FST Type I skin always burns, never tans (pale white; blond or red hair; blue, gray eyes; freckles), FST Type II skin usually burns, tans minimally (white; blond, brown or red hair; blue, green, or hazel eyes), FST Type III skin sometimes has a mild burn, tans uniformly (cream white; yellowish; any hair color or brown eyes), FST Type IV skin burns minimally, always tans well (light brown; olive; dark brown to black hair), FST Type V skin very rarely burns, tans very easily (brown), FST Type VI skin never burns, always tans (deeply pigmented dark brown to darkest brown, black in complexion)

Outcome Measures

1. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Optimal Correction Group	Retreatment Group
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	41	30
Overall Number of Units Analyzed; Type of Units Analyzed: Nasolabial Folds	81	60
Mean (Standard Deviation); Unit of Measure: units on WSRS scale
Change in Main Study Treatment - Revanesse Ultra	0.1 (0.69)	0.6 (0.72)
Change in Main Study Treatment - Restylane	0.0 (0.69)	0.8 (0.63)

2. Secondary Outcome

Title	Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Revanesse Ultra Retreatment	Revanesse Ultra Optimal Correction
Arm/Group Description:	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	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 Number of Participants Analyzed	30	41
Measure Type: Count of Participants; Unit of Measure: Participants
Eye disorder - ocular hyperaemia	0 0.0%	1 2.4%
Gastrointestinal - mouth cyst	0 0.0%	1 2.4%
Injection site erythema	2 6.7%	8 19.5%
Injection site haematoma	9 30.0%	19 46.3%
Injection site mass	1 3.3%	2 4.9%
Injection site pain	9 30.0%	6 14.6%
Injection site pruritis	0 0.0%	1 2.4%
Injection site swelling	0 0.0%	1 2.4%
Contusion	0 0.0%	1 2.4%
Excoriation	0 0.0%	1 2.4%

3. Secondary Outcome

Title	Patient Global Aesthetic Improvement (pGAI) Score
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Revanesse Ultra Retreatment	Revanesse Ultra Optimal Correction
Arm/Group Description:	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	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 Number of Participants Analyzed	30	41
Measure Type: Count of Participants; Unit of Measure: Participants
Visit 8 - week 52 pGAI = 1 worse	1 3.3%	1 2.4%
Visit 8 - week 52 pGAI = 2 no change	8 26.7%	8 19.5%
Visit 8 - week 52 pGAI = 3 Improved	13 43.3%	16 39.0%
Visit 8 - week 52 pGAI = 4 much improved	1 3.3%	12 29.3%
Visit 8 - week 52 pGAI = 5 Very much improved	7 23.3%	4 9.8%

Adverse Events

Time Frame	Adverse Event data was collected at Retreatment for 6 months (Visit 8/Week 52 from the Main Study)
Adverse Event Reporting Description	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.
Arm/Group Title	Retreatment Group		Optimal Correction Group
Arm/Group Description	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).		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).
All-Cause Mortality
	Retreatment Group		Optimal Correction Group
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/30 (0.00%)		0/41 (0.00%)
Serious Adverse Events
	Retreatment Group		Optimal Correction Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0.00%)		0/41 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Retreatment Group		Optimal Correction Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/30 (53.33%)		29/41 (70.73%)
General disorders
INJECTION SITE ERYTHEMA * 1 [1]	2/30 (6.67%)	2	9/41 (21.95%)	9
INJECTION SITE HAEMATOMA * 1 [2]	9/30 (30.00%)	9	19/41 (46.34%)	19
INJECTION SITE PAIN * 1 [3]	9/30 (30.00%)	9	6/41 (14.63%)	6
INJECTION SITE SWELLING * 1 [4]	9/30 (30.00%)	9	14/41 (34.15%)	14
1 Term from vocabulary, MedDRA (15.1); * Indicates events were collected by non-systematic assessment; [1] Counts reflect numbers of subjects reporting one or more injection site TEAEs that map to the MedDRA (version 15.1). At each level of summarization (SOC or preferred term) subjects reporting more than one injection site TEAE are only counted once.; [2] bruising; [3] pain at the injection site; [4] Swelling at the injection site

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Ario Khoshbin, President
• Organization: Prollenium Medical Technologies, Inc.
• Phone: 866-353-3015

• Responsible Party: Prollenium Medical Technologies Inc.
• ClinicalTrials.gov Identifier: NCT02984878
• Other Study ID Numbers: SYM2014-02 Retreatment
• First Submitted: December 5, 2016
• First Posted: December 7, 2016
• Results First Submitted: August 28, 2017
• Results First Posted: December 20, 2017
• Last Update Posted: December 20, 2017