Trial Outcomes & Findings for EN3835 for the Treatment of Edematous Fibrosclerotic Panniculopathy (Commonly Known as Cellulite) (NCT NCT02724644)

NCT ID: NCT02724644

Last Updated: 2017-11-06

Results Overview

Percentage of composite responders defined as subjects with an improvement from baseline of at least 2-levels of severity on each, the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), at Day 71 in the ITT population. The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement on each scale for example would represent a change from a 4 (severe) to a 2 (mild). In order to be considered a responder a subject needs to have at least a 2-level improvement on both scales.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

375 participants

Primary outcome timeframe

Baseline, Day 71

Results posted on

2017-11-06

Participant Flow

Participant milestones

Participant milestones
Measure
EN3835 0.84 mg
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Study
STARTED
189
186
Overall Study
COMPLETED
168
182
Overall Study
NOT COMPLETED
21
4

Reasons for withdrawal

Reasons for withdrawal
Measure
EN3835 0.84 mg
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Study
Adverse Event
7
1
Overall Study
Lost to Follow-up
6
2
Overall Study
Withdrawal by Subject
7
1
Overall Study
Administrative
1
0

Baseline Characteristics

EN3835 for the Treatment of Edematous Fibrosclerotic Panniculopathy (Commonly Known as Cellulite)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
EN3835 0.84 mg
n=189 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=186 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Total
n=375 Participants
Total of all reporting groups
Age, Continuous
47.2 Participants
STANDARD_DEVIATION 11.21 • n=5 Participants
45.8 Participants
STANDARD_DEVIATION 11.02 • n=7 Participants
46.5 Participants
STANDARD_DEVIATION 11.13 • n=5 Participants
Age, Customized
18-<25 years
8 Participants
n=5 Participants
9 Participants
n=7 Participants
17 Participants
n=5 Participants
Age, Customized
25-34 years
18 Participants
n=5 Participants
21 Participants
n=7 Participants
39 Participants
n=5 Participants
Age, Customized
35-44 years
46 Participants
n=5 Participants
47 Participants
n=7 Participants
93 Participants
n=5 Participants
Age, Customized
>=45 years
117 Participants
n=5 Participants
109 Participants
n=7 Participants
226 Participants
n=5 Participants
Sex: Female, Male
Female
189 Participants
n=5 Participants
186 Participants
n=7 Participants
375 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
37 Participants
n=5 Participants
41 Participants
n=7 Participants
78 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
152 Participants
n=5 Participants
145 Participants
n=7 Participants
297 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
Race (NIH/OMB)
Asian
3 Participants
n=5 Participants
1 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
15 Participants
n=5 Participants
26 Participants
n=7 Participants
41 Participants
n=5 Participants
Race (NIH/OMB)
White
167 Participants
n=5 Participants
157 Participants
n=7 Participants
324 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
3 Participants
n=5 Participants
0 Participants
n=7 Participants
3 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
189 Participants
n=5 Participants
186 Participants
n=7 Participants
375 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 71

Population: Analysis is based on ITT population; all randomized subjects who received at least 1 injection of study medication

Percentage of composite responders defined as subjects with an improvement from baseline of at least 2-levels of severity on each, the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), at Day 71 in the ITT population. The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement on each scale for example would represent a change from a 4 (severe) to a 2 (mild). In order to be considered a responder a subject needs to have at least a 2-level improvement on both scales.

Outcome measures

Outcome measures
Measure
EN3835 0.84 mg
n=189 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=186 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Percentage of Composite Responders of at Least 2-Level Improvement of Severity
20 Participants
3 Participants

SECONDARY outcome

Timeframe: Baseline, Day 71

Population: Analysis is based on ITT population; all randomized subjects who received at least 1 injection of study medication

Percentage of composite responders defined as subjects with improvement from baseline of at least 1-level of severity on each, the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), at Day 71 in the ITT population. The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 1-level improvement on each scale for example would represent a change from a 4 (severe) to a 3 (moderate). In order to be considered a responder a subject needs to have at least a 1-level improvement on both scales.

Outcome measures

Outcome measures
Measure
EN3835 0.84 mg
n=189 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=186 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Percentage of Composite Responders of at Least 1-Level Improvement of Severity
79 Participants
33 Participants

SECONDARY outcome

Timeframe: Baseline, Day 71

Population: Analysis is based on modified intent-to-treat (mITT) population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS

Percentage of subjects with improvement from baseline of at least 2-levels of severity on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) at Day 71.The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement would be for example a change from 4 (severe) to 2 (mild).

Outcome measures

Outcome measures
Measure
EN3835 0.84 mg
n=177 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=184 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
CR-PCSS Responder Analysis: 2-Levels of Severity
32 Participants
9 Participants

SECONDARY outcome

Timeframe: Baseline, Day 71

Population: Analysis is based on modified intent-to-treat (mITT) population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS

Percentage of subjects with improvement from baseline of at least 1-level of severity on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) at Day 71.The CR-PCSS is a photonumeric scale that was used by the investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 1-level improvement would be for example a change from 4 (severe) to 3 (moderate).

Outcome measures

Outcome measures
Measure
EN3835 0.84 mg
n=177 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=184 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
CR-PCSS Responder Analysis: 1-Level of Severity
96 Participants
53 Participants

SECONDARY outcome

Timeframe: Baseline, Day 71

Population: Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS

The CR-PCSS is a photonumeric scale that was used by the investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). Change is Day 71 study visit rating minus baseline visit; negative values indicate a lessening in cellulite severity.

Outcome measures

Outcome measures
Measure
EN3835 0.84 mg
n=177 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=184 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
CR-PCSS Change From Baseline
-0.7 units on a scale
Standard Deviation 0.83
-0.3 units on a scale
Standard Deviation 0.62

SECONDARY outcome

Timeframe: Baseline, Day 71

Population: Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS

Percentage of subjects with improvement from baseline of at least 2-levels of severity on the subject-rated Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) at Day 71.The PR-PCSS is a photonumeric scale that was used by the subject to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement would be for example a change from 4 (severe) to 2 (mild).

Outcome measures

Outcome measures
Measure
EN3835 0.84 mg
n=177 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=184 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
PR-PCSS Responder Analysis: 2-Levels of Severity
51 Participants
24 Participants

SECONDARY outcome

Timeframe: Baseline, Day 71

Population: Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS

Percentage of subjects with improvement from baseline of at least 1-level of severity on the subject-rated Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) at Day 71.The PR-PCSS is a photonumeric scale that was used by the subject to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 1-level improvement would be for example a change from 4 (severe) to 3 (moderate).

Outcome measures

Outcome measures
Measure
EN3835 0.84 mg
n=177 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=184 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
PR-PCSS Responder Analysis: 1-Level of Severity
128 Participants
95 Participants

SECONDARY outcome

Timeframe: Baseline, Day 71

Population: Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS

The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). Change is Day 71 study visit rating minus baseline visit; negative values indicate a lessening in cellulite severity.

Outcome measures

Outcome measures
Measure
EN3835 0.84 mg
n=177 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=184 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
PR-PCSS Change From Baseline
-1.0 units on a scale
Standard Deviation 0.89
-0.7 units on a scale
Standard Deviation 0.79

SECONDARY outcome

Timeframe: Day 71

Population: Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS

On Day 71, the Investigator determined the degree of improvement from baseline in the treated area using the 7-point I-GAIS. Ratings could be improved (+1), much improved (+2), or very much improved (+3), or no change (0), or worse (-1), much worse (-2) or very much worse (-3).

Outcome measures

Outcome measures
Measure
EN3835 0.84 mg
n=177 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=184 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Investigator Assessment of Improvement Based on the Investigator Global Aesthetic Improvement Scale (I-GAIS)
Very Much Improved (3)
6 Participants
2 Participants
Investigator Assessment of Improvement Based on the Investigator Global Aesthetic Improvement Scale (I-GAIS)
Much improved (2)
40 Participants
15 Participants
Investigator Assessment of Improvement Based on the Investigator Global Aesthetic Improvement Scale (I-GAIS)
Improved (1)
64 Participants
43 Participants
Investigator Assessment of Improvement Based on the Investigator Global Aesthetic Improvement Scale (I-GAIS)
No Change( 0)
57 Participants
119 Participants
Investigator Assessment of Improvement Based on the Investigator Global Aesthetic Improvement Scale (I-GAIS)
Worse (-1)
6 Participants
4 Participants
Investigator Assessment of Improvement Based on the Investigator Global Aesthetic Improvement Scale (I-GAIS)
Much worse (-2)
2 Participants
0 Participants
Investigator Assessment of Improvement Based on the Investigator Global Aesthetic Improvement Scale (I-GAIS)
Very Much Worse (-3)
0 Participants
0 Participants
Investigator Assessment of Improvement Based on the Investigator Global Aesthetic Improvement Scale (I-GAIS)
Not done
2 Participants
1 Participants

SECONDARY outcome

Timeframe: Day 71

Population: Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS

At Day 71, subjects were asked to rate their opinion of the overall improvement of their treated area using the 7-point S-GAIS. Ratings could be improved (+1), much improved (+2), or very much improved (+3), or no change (0), or worse (-1), much worse (-2) or very much worse (-3)

Outcome measures

Outcome measures
Measure
EN3835 0.84 mg
n=177 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=184 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Subject Assessment of Improvement Based on the Subject Global Aesthetic Improvement Scale (S-GAIS)
Very Much Improved (3)
21 Participants
11 Participants
Subject Assessment of Improvement Based on the Subject Global Aesthetic Improvement Scale (S-GAIS)
Much Improved (2)
43 Participants
17 Participants
Subject Assessment of Improvement Based on the Subject Global Aesthetic Improvement Scale (S-GAIS)
Improved (1)
64 Participants
52 Participants
Subject Assessment of Improvement Based on the Subject Global Aesthetic Improvement Scale (S-GAIS)
No change (0)
38 Participants
97 Participants
Subject Assessment of Improvement Based on the Subject Global Aesthetic Improvement Scale (S-GAIS)
Worse (-1)
6 Participants
5 Participants
Subject Assessment of Improvement Based on the Subject Global Aesthetic Improvement Scale (S-GAIS)
Much Worse (-2)
3 Participants
0 Participants
Subject Assessment of Improvement Based on the Subject Global Aesthetic Improvement Scale (S-GAIS)
Very Much Worse (-3)
0 Participants
0 Participants
Subject Assessment of Improvement Based on the Subject Global Aesthetic Improvement Scale (S-GAIS)
Not done
2 Participants
2 Participants

SECONDARY outcome

Timeframe: Day 71

Population: Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS

At Day 71, subjects were asked to rate their satisfaction with cellulite treatment using the 5-point subject satisfaction scale. Ratings could be satisfied (+1), very satisfied (+2), neither satisfied nor dissatisfied (0), or dissatisfied (-1), very dissatisfied (-2).

Outcome measures

Outcome measures
Measure
EN3835 0.84 mg
n=177 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=184 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Subject Satisfaction Assessment Based on the the Subject Satisfaction Scale
Not done
2 Participants
3 Participants
Subject Satisfaction Assessment Based on the the Subject Satisfaction Scale
Very Satisfied (2)
41 Participants
25 Participants
Subject Satisfaction Assessment Based on the the Subject Satisfaction Scale
Satisfied (1)
69 Participants
40 Participants
Subject Satisfaction Assessment Based on the the Subject Satisfaction Scale
Neither Satisfied nor Dissatisfied (0)
45 Participants
82 Participants
Subject Satisfaction Assessment Based on the the Subject Satisfaction Scale
Dissatisfied (-1)
11 Participants
18 Participants
Subject Satisfaction Assessment Based on the the Subject Satisfaction Scale
Very Dissatisfied (-2)
9 Participants
16 Participants

SECONDARY outcome

Timeframe: Baseline, Day 71

Population: Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS

Investigator used the Hexsel CSS to assess the severity of cellulite. The total score could range from 0 (no cellulite) to 15 (extremely severe cellulite). Negative change in Hexsel CSS total score indicates an improvement in cellulite severity

Outcome measures

Outcome measures
Measure
EN3835 0.84 mg
n=177 Participants
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=184 Participants
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Change in the Hexsel Cellulite Severity Scale (CSS) Total Score
-1.7 units on a scale
Standard Deviation 2.20
-0.9 units on a scale
Standard Deviation 2.00

Adverse Events

EN3835 0.84 mg

Serious events: 1 serious events
Other events: 148 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 30 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
EN3835 0.84 mg
n=189 participants at risk
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=186 participants at risk
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
0.53%
1/189 • Number of events 1 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
0.00%
0/186 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)

Other adverse events

Other adverse events
Measure
EN3835 0.84 mg
n=189 participants at risk
Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days. Injectable intervention
Placebo
n=186 participants at risk
Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
General disorders
Injection site bruising
75.1%
142/189 • Number of events 314 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
13.4%
25/186 • Number of events 33 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
General disorders
Injection site pain
59.3%
112/189 • Number of events 228 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
5.4%
10/186 • Number of events 11 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
General disorders
Injection site nodule
14.3%
27/189 • Number of events 33 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
0.00%
0/186 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
General disorders
Injection site pruritus
11.1%
21/189 • Number of events 29 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
0.54%
1/186 • Number of events 1 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
General disorders
Injection site induration
5.8%
11/189 • Number of events 17 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
0.00%
0/186 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
General disorders
Injection site swelling
7.4%
14/189 • Number of events 17 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
0.54%
1/186 • Number of events 2 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
General disorders
Injection site mass
5.3%
10/189 • Number of events 12 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)
0.54%
1/186 • Number of events 1 • Baseline, Day 71
Serious Adverse Events by Frequency (Safety Population)

Additional Information

Clinical Trial Coordinator

Endo Pharmaceuticals Inc.

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: OTHER