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Effectiveness and Safety of EN3835 in the Treatment of Cellulite in Women (RELEASE-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03446781
Recruitment Status : Completed
First Posted : February 27, 2018
Results First Posted : October 8, 2020
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
Endo Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Edematous Fibrosclerotic Panniculopathy (Cellulite)
Interventions Biological: EN3835
Biological: Placebo
Enrollment 422
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Collagenase Clostridium Histolyticum (CCH) Placebo
Hide Arm/Group Description CCH 0.84 mg/Buttock 1.68 mg Total Dose Placebo-control
Period Title: Overall Study
Started 214 208
Completed 186 191
Not Completed 28 17
Reason Not Completed
Lost to Follow-up             11             5
Withdrawal by Subject             9             7
Adverse Event             8             2
Protocol Violation             0             3
Arm/Group Title Collagenase Clostridium Histolyticum (CCH) Placebo Total
Hide Arm/Group Description CCH 0.84 mg/Buttock 1.68 mg Total Dose Placebo-control Total of all reporting groups
Overall Number of Baseline Participants 214 206 420
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 214 participants 206 participants 420 participants
47.7  (10.62) 45.7  (11.16) 46.7  (10.92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 214 participants 206 participants 420 participants
Female
214
 100.0%
206
 100.0%
420
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 214 participants 206 participants 420 participants
Hispanic or Latino
46
  21.5%
58
  28.2%
104
  24.8%
Not Hispanic or Latino
168
  78.5%
148
  71.8%
316
  75.2%
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 214 participants 206 participants 420 participants
American Indian or Alaska Native
3
   1.4%
5
   2.4%
8
   1.9%
Asian
0
   0.0%
1
   0.5%
1
   0.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
29
  13.6%
32
  15.5%
61
  14.5%
White
179
  83.6%
164
  79.6%
343
  81.7%
More than one race
2
   0.9%
2
   1.0%
4
   1.0%
Unknown or Not Reported
1
   0.5%
2
   1.0%
3
   0.7%
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 214 participants 206 participants 420 participants
30.52  (6.184) 31.14  (7.567) 30.82  (6.896)
Skin Category (Fitzpatrick Scale)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 214 participants 206 participants 420 participants
I (Pale White)
6
   2.8%
8
   3.9%
14
   3.3%
II (Fair)
74
  34.6%
54
  26.2%
128
  30.5%
III (Darker White)
50
  23.4%
64
  31.1%
114
  27.1%
IV (Light Brown)
53
  24.8%
47
  22.8%
100
  23.8%
V (Brown)
15
   7.0%
18
   8.7%
33
   7.9%
VI (Dark Brown)
16
   7.5%
15
   7.3%
31
   7.4%
1.Primary Outcome
Title 2-level Composite Responders for the Target Buttock
Hide Description Proportion of 2-level Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) / Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) composite responders in the target buttock at Day 71. CR-PCSS and PR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe). A 2-level composite responder is defined as a participant with improvement from baseline of at least 2-levels of severity in the CR-PCSS and an improvement from baseline of at least 2-levels of severity in the PR-PCSS of the target buttock. A participant who missed one or two assessments of CR-PCSS and PR-PCSS at Day 71 was defined as a non-responder.
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population includes all randomized participants who had at least 1 injection of study drug. All demographic and baseline characteristic summaries were based on this population. The primary and key secondary efficacy parameters were summarized based on this population.
Arm/Group Title Collagenase Clostridium Histolyticum (CCH) Placebo
Hide Arm/Group Description:
CCH 0.84 mg/Buttock
Placebo-control
Overall Number of Participants Analyzed 214 206
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
12
   5.6%
1
   0.5%
No
202
  94.4%
205
  99.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Collagenase Clostridium Histolyticum (CCH), Placebo
Comments CCH 0.84 mg/Buttock versus Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Adjusted for analysis center
2.Secondary Outcome
Title 1-level PR-PCSS Responders of the Target Buttock
Hide Description Improvement in cellulite severity of the Target Buttock from baseline of at least 1-level of severity in Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS). PR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe).
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population includes all randomized participants who had at least 1 injection of study drug. All demographic and baseline characteristic summaries were based on this population. The primary and key secondary efficacy parameters were summarized based on this population.
Arm/Group Title Collagenase Clostridium Histolyticum (CCH) Placebo
Hide Arm/Group Description:
CCH 0.84 mg/Buttock
Placebo-control
Overall Number of Participants Analyzed 214 206
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
124
  57.9%
61
  29.6%
No
90
  42.1%
145
  70.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Collagenase Clostridium Histolyticum (CCH), Placebo
Comments CCH 0.84 mg/Buttock versus Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Adjusted for analysis center
3.Secondary Outcome
Title 2-level PR-PCSS Responders of the Target Buttock
Hide Description Improvement in cellulite severity of the Target Buttock from baseline of at least 2-levels of severity in Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS). PR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe).
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population includes all randomized participants who had at least 1 injection of study drug. All demographic and baseline characteristic summaries were based on this population. The primary and key secondary efficacy parameters were summarized based on this population.
Arm/Group Title Collagenase Clostridium Histolyticum (CCH) Placebo
Hide Arm/Group Description:
CCH 0.84 mg/Buttock
Placebo-control
Overall Number of Participants Analyzed 214 206
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
45
  21.0%
12
   5.8%
No
169
  79.0%
194
  94.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Collagenase Clostridium Histolyticum (CCH), Placebo
Comments CCH 0.84 mg/Buttock versus Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Adjusted for analysis center
4.Secondary Outcome
Title 1-level Composite Responders of the Target Buttock
Hide Description Improvement in cellulite severity of the Target Buttock from baseline of at least 1-level of severity in Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) / Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS). PR-PCSS and CR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe).
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population includes all randomized participants who had at least 1 injection of study drug. All demographic and baseline characteristic summaries were based on this population. The primary and key secondary efficacy parameters were summarized based on this population.
Arm/Group Title Collagenase Clostridium Histolyticum (CCH) Placebo
Hide Arm/Group Description:
CCH 0.84 mg/Buttock
Placebo-control
Overall Number of Participants Analyzed 214 206
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
89
  41.6%
23
  11.2%
No
125
  58.4%
183
  88.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Collagenase Clostridium Histolyticum (CCH), Placebo
Comments CCH 0.84 mg/Buttock versus Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Adjusted for analysis center
5.Secondary Outcome
Title 2-level Composite Responders of the Non-target Buttock
Hide Description Improvement in cellulite severity of the Non-target Buttock from baseline of at least 2-levels of severity in Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) / Clinician -Reported Photonumeric Cellulite Severity Scale (CR-PCSS). PR-PCSS and CR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe).
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population includes all randomized participants who had at least 1 injection of study drug. All demographic and baseline characteristic summaries were based on this population. The primary and key secondary efficacy parameters were summarized based on this population.
Arm/Group Title Collagenase Clostridium Histolyticum (CCH) Placebo
Hide Arm/Group Description:
CCH 0.84 mg/Buttock
Placebo-control
Overall Number of Participants Analyzed 214 206
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
13
   6.1%
4
   1.9%
No
201
  93.9%
202
  98.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Collagenase Clostridium Histolyticum (CCH), Placebo
Comments CCH 0.84 mg/Buttock versus Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Adjusted for analysis center
6.Secondary Outcome
Title 1-level SSRS Responders
Hide Description Subject Self-Rating Scale (SSRS) is a measure that assesses participant satisfaction with appearance in association with cellulite on the buttocks using whole numbers on a 7-level scale that ranges from "0" (Extremely Dissatisfied) to "6" (Extremely Satisfied). A 1-level SSRS responder is defined as a participant who is at least slightly satisfied (Slightly Satisfied [4], Very Satisfied [5], or Extremely Satisfied [6]) with the appearance of the cellulite on her buttocks at Day 71.
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population includes all randomized participants who had at least 1 injection of study drug. All demographic and baseline characteristic summaries were based on this population. The primary and key secondary efficacy parameters were summarized based on this population.
Arm/Group Title Collagenase Clostridium Histolyticum (CCH) Placebo
Hide Arm/Group Description:
CCH 0.84 mg/Buttock (1.68 mg Total Dose)
Placebo-control
Overall Number of Participants Analyzed 214 206
Measure Type: Count of Participants
Unit of Measure: Participants
90
  42.1%
31
  15.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Collagenase Clostridium Histolyticum (CCH), Placebo
Comments CCH 0.84 mg/Buttock versus Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Adjusted for analysis center
7.Secondary Outcome
Title Change From Baseline in PR-CIS Total Score
Hide Description Patient-Reported Cellulite Impact Scale (PR-CIS) is a 6-item static questionnaire, each item is answered by a participant on a 11-level numerical rating scale that ranges from "0" (Not at all) to "10" (Extremely). The PR-CIS total score is the sum of individual item scores and can range from "0" to "60" with higher numbers reflecting a more negative impact from the cellulite. A responder is defined as a participant with a reduction in the PR-CIS total score of at least 12 from baseline at evaluation time point. A negative change from baseline indicates an improvement in cellulite severity.
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population includes all randomized participants who had at least 1 injection of study drug. All demographic and baseline characteristic summaries were based on this population. The primary and key secondary efficacy parameters were summarized based on this population.
Arm/Group Title Collagenase Clostridium Histolyticum (CCH) Placebo
Hide Arm/Group Description:
CCH 0.84 mg/Buttock (1.68 mg Total Dose)
Placebo-control
Overall Number of Participants Analyzed 214 206
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline (Day 1) Number Analyzed 213 participants 202 participants
52.4  (8.01) 51.6  (9.40)
Day 71 Number Analyzed 214 participants 206 participants
40.9  (13.57) 45.1  (12.65)
Change from Baseline Number Analyzed 213 participants 202 participants
-11.5  (12.74) -6.5  (11.74)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Collagenase Clostridium Histolyticum (CCH), Placebo
Comments CCH 0.84 mg/Buttock versus Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments With factors of treatment group and analysis center adjusted for baseline values in the model
8.Secondary Outcome
Title 1-level S-GAIS Responders of Target Buttock
Hide Description Subject Global Aesthetic Improvement Scale (S-GAIS) is a measure that assesses participant rating of cellulite appearance after treatment. This scale has 7-levels ranging from "+3" (Very Much Improved) to "-3" (Very Much Worse). Responders are defined as participants with ≥1-level improvement (Improved, Much Improved or Very Improved) in S-GAIS assessment of the Target Buttock.
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population includes all randomized participants who had at least 1 injection of study drug. All demographic and baseline characteristic summaries were based on this population. The primary and key secondary efficacy parameters were summarized based on this population.
Arm/Group Title Collagenase Clostridium Histolyticum (CCH) Placebo
Hide Arm/Group Description:
CCH 0.84 mg/Buttock
Placebo-control
Overall Number of Participants Analyzed 214 206
Measure Type: Count of Participants
Unit of Measure: Participants
126
  58.9%
46
  22.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Collagenase Clostridium Histolyticum (CCH), Placebo
Comments CCH 0.84 mg/Buttock versus Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Adjusted for analysis center
9.Secondary Outcome
Title 2-level S-GAIS Responders of Target Buttock
Hide Description Subject Global Aesthetic Improvement Scale (S-GAIS) is a measure that assesses participant rating of cellulite appearance after treatment. This scale has 7-levels ranging from "+3" (Very Much Improved) to "-3" (Very Much Worse). Responders are defined as participants with ≥ 2-level improvement (Much Improved or Very Much Improved) in S-GAIS assessment of the Target Buttock.
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population includes all randomized participants who had at least 1 injection of study drug. All demographic and baseline characteristic summaries were based on this population. The primary and key secondary efficacy parameters were summarized based on this population.
Arm/Group Title Collagenase Clostridium Histolyticum (CCH) Placebo
Hide Arm/Group Description:
CCH 0.84 mg/Buttock
Placebo-control
Overall Number of Participants Analyzed 214 206
Measure Type: Count of Participants
Unit of Measure: Participants
38
  17.8%
9
   4.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Collagenase Clostridium Histolyticum (CCH), Placebo
Comments CCH 0.84 mg/Buttock versus Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Adjusted for analysis center
10.Secondary Outcome
Title PR-PCSS Rating for the Target and Non-target Buttock by Visit
Hide Description The Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) is a 5-level photonumeric scale used by the patient (participant) to assess the severity of the participant's cellulite. The ratings range from "0" (None) to "4" (Severe).
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population includes all ITT participants with a baseline and at least 1 post-injection evaluation of both the CR-PCSS and PR-PCSS for both the target and non-target buttocks. All secondary and supportive efficacy evaluations were based on the mITT Population.
Arm/Group Title Day 1: CCH Day 1: Placebo Day 22: CCH Day 22: Placebo Day 43: CCH Day 43: Placebo Day 71: CCH Day 71: Placebo Day 71: CCH (LOCF) Day 71: Placebo (LOCF)
Hide Arm/Group Description:
Baseline (Day 1) for CCH Treated Group
Baseline (Day 1) for PlaceboGroup
Day 22 for CCH Treated Group
Day 22 for Placebo Group
Day 43 for CCH Treated Group
Day 43 for Placebo Group
Day 71 for CCH Treated Group
Day 71 for Placebo Group
Day 71 for CCH Treated Group (Last Observation Carried Forward)
Day 71 for Placebo Group (Last Observation Carried Forward)
Overall Number of Participants Analyzed 209 201 209 201 209 201 209 201 209 201
Measure Type: Count of Participants
Unit of Measure: Participants
Target Buttock Rating Number Analyzed 209 participants 201 participants 197 participants 199 participants 186 participants 191 participants 186 participants 191 participants 209 participants 201 participants
None (0)
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.5%
0
   0.0%
0
   0.0%
3
   1.6%
0
   0.0%
3
   1.4%
0
   0.0%
Almost None (1)
0
   0.0%
0
   0.0%
1
   0.5%
1
   0.5%
17
   9.1%
3
   1.6%
19
  10.2%
2
   1.0%
19
   9.1%
2
   1.0%
Mild (2)
0
   0.0%
0
   0.0%
45
  22.8%
17
   8.5%
61
  32.8%
26
  13.6%
61
  32.8%
32
  16.8%
64
  30.6%
32
  15.9%
Moderate (3)
89
  42.6%
82
  40.8%
78
  39.6%
79
  39.7%
67
  36.0%
85
  44.5%
65
  34.9%
76
  39.8%
76
  36.4%
81
  40.3%
Severe (4)
120
  57.4%
119
  59.2%
73
  37.1%
101
  50.8%
41
  22.0%
77
  40.3%
38
  20.4%
81
  42.4%
47
  22.5%
86
  42.8%
Non-target Buttock Rating Number Analyzed 209 participants 201 participants 197 participants 199 participants 186 participants 191 participants 186 participants 191 participants 209 participants 201 participants
None (0)
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.5%
0
   0.0%
0
   0.0%
1
   0.5%
0
   0.0%
1
   0.5%
0
   0.0%
Almost None (1)
0
   0.0%
0
   0.0%
3
   1.5%
0
   0.0%
17
   9.1%
4
   2.1%
21
  11.3%
3
   1.6%
21
  10.0%
3
   1.5%
Mild (2)
0
   0.0%
0
   0.0%
38
  19.3%
19
   9.5%
55
  29.6%
24
  12.6%
58
  31.2%
32
  16.8%
64
  30.6%
34
  16.9%
Moderate (3)
96
  45.9%
71
  35.3%
82
  41.6%
71
  35.7%
67
  36.0%
86
  45.0%
66
  35.5%
72
  37.7%
74
  35.4%
75
  37.3%
Severe (4)
113
  54.1%
130
  64.7%
74
  37.6%
108
  54.3%
47
  25.3%
77
  40.3%
40
  21.5%
84
  44.0%
49
  23.4%
89
  44.3%
11.Secondary Outcome
Title Subjects Satisfaction With Cellulite Treatment
Hide Description A 1-level Subject Satisfaction Responder is defined as a participant who is at least satisfied (Satisfied [+1], or Very Satisfied [+2]) with the appearance of the cellulite on her buttocks at the Day 71 visit. A positive change indicates an improvement in cellulite.
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population includes all ITT participants with a baseline and at least 1 post-injection evaluation of both the CR-PCSS and PR-PCSS for both the target and non-target buttocks. All secondary and supportive efficacy evaluations were based on the mITT Population.
Arm/Group Title Day 71: CCH Day 71: Placebo Day 71: CCH (LOCF) Day 71: Placebo (LOCF)
Hide Arm/Group Description:
Day 71 for CCH Treated Group
Day 71 for Placebo Group
Day 71 for CCH Treated Group (Last Observation Carried Forward)
Day 71 for Placebo Group (Last Observation Carried Forward)
Overall Number of Participants Analyzed 186 191 198 195
Measure Type: Count of Participants
Unit of Measure: Participants
Very Satisfied (+2)
15
   8.1%
4
   2.1%
15
   7.6%
4
   2.1%
Satisfied (+1)
72
  38.7%
22
  11.5%
74
  37.4%
22
  11.3%
Neither Satisfied Nor Dissatisfied (0)
60
  32.3%
73
  38.2%
64
  32.3%
75
  38.5%
Dissatisfied (-1)
24
  12.9%
47
  24.6%
29
  14.6%
48
  24.6%
Very Dissatisfied (-2)
15
   8.1%
45
  23.6%
16
   8.1%
46
  23.6%
12.Other Pre-specified Outcome
Title Serum Antibody Positivity by Visit
Hide Description Percent of participants that are seropositive. Percentages were based on the number of subjects who had immunogenicity lab samples analyzed at the visit.
Time Frame Day 1 - Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population includes all participants who received at least 1 dose of CCH in this study. All safety parameters were summarized based on this population.
Arm/Group Title Anti-AUX-I: CCH Anti-AUX-I: Placebo Anti-AUX-II: CCH Anti-AUX-II: Placebo
Hide Arm/Group Description:
Antibody AUX-I for the CCH Treated Group
Antibody AUX-I for the Placebo Group
Antibody AUX-II for the CCH Treated Group
Antibody AUX-II for the Placebo Group
Overall Number of Participants Analyzed 214 206 214 206
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1 Number Analyzed 214 participants 206 participants 214 participants 206 participants
Seropositive
6
   2.8%
2
   1.0%
3
   1.4%
6
   2.9%
Seronegative
208
  97.2%
204
  99.0%
211
  98.6%
200
  97.1%
Day 22 Number Analyzed 196 participants 199 participants 196 participants 199 participants
Seropositive
106
  54.1%
1
   0.5%
52
  26.5%
7
   3.5%
Seronegative
90
  45.9%
198
  99.5%
144
  73.5%
192
  96.5%
Day 43 Number Analyzed 186 participants 190 participants 186 participants 190 participants
Seropositive
183
  98.4%
4
   2.1%
183
  98.4%
7
   3.7%
Seronegative
3
   1.6%
186
  97.9%
3
   1.6%
183
  96.3%
Day 71 Number Analyzed 186 participants 190 participants 186 participants 190 participants
Seropositive
186
 100.0%
8
   4.2%
185
  99.5%
9
   4.7%
Seronegative
0
   0.0%
182
  95.8%
1
   0.5%
181
  95.3%
13.Other Pre-specified Outcome
Title Overall Antibody Titer Levels by Visit
Hide Description Descriptive statistics were based on log10 transformation of titer levels. Titer levels were imputed as 10 before the transformation if the reported level is "<10". Only seropositive participants are summarized.
Time Frame Day 1 - Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population includes all participants who received at least 1 dose of CCH in this study. All safety parameters were summarized based on this population.
Arm/Group Title Anti-AUX-I: CCH Anti-AUX-I: Placebo Anti-AUX-II: CCH Anti-AUX-II: Placebo
Hide Arm/Group Description:
Antibody AUX-I for the CCH Treated Group
Antibody AUX-I for the Placebo Group
Antibody AUX-II for the CCH Treated Group
Antibody AUX-II for the Placebo Group
Overall Number of Participants Analyzed 214 206 214 206
Mean (Standard Deviation)
Unit of Measure: log 10 titer
Day 1 positive Number Analyzed 6 participants 2 participants 3 participants 6 participants
2.235  (1.7365) 1.000  (0.0000) 3.212  (0.8056) 1.365  (0.3834)
Day 22 positive Number Analyzed 106 participants 1 participants 52 participants 7 participants
2.331  (1.2566) 3.504 1.912  (1.2718) 1.387  (0.4788)
Day 43 positive Number Analyzed 183 participants 4 participants 183 participants 7 participants
4.602  (0.8721) 2.539  (1.1462) 3.680  (1.0617) 1.302  (0.4596)
Day 71 positive Number Analyzed 186 participants 8 participants 185 participants 9 participants
5.898  (0.7131) 2.039  (1.2854) 5.255  (0.7142) 1.572  (0.7895)
14.Other Pre-specified Outcome
Title Presence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles
Hide Description Q1 and Q4 are based on the ADA titer levels.
Time Frame Day 71
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Hide Analysis Population Description
Safety Population includes all participants who received at least 1 dose of CCH in this study. All safety parameters were summarized based on this population.
Arm/Group Title CCH: Q1 CCH: Q4 CCH: Total
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Q1 for the CCH Treated Group
Q4 for the CCH Treated Group
Total CCH
Overall Number of Participants Analyzed 24 24 48
Measure Type: Count of Participants
Unit of Measure: Participants
Neutralizing AUX-I Antibody Negative
12
  50.0%
3
  12.5%
15
  31.3%
Positive
12
  50.0%
21
  87.5%
33
  68.8%
Neutralizing AUX-II Antibody Negative
5
  20.8%
1
   4.2%
6
  12.5%
Positive
19
  79.2%
23
  95.8%
42
  87.5%
Time Frame All (serious and nonserious) AEs, from Day 1 to Day 71
Adverse Event Reporting Description All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
 
Arm/Group Title Collagenase Clostridium Histolyticum (CCH) Placebo
Hide Arm/Group Description CCH 0.84 mg/Buttock 1.68 mg Total Dose Placebo-control
All-Cause Mortality
Collagenase Clostridium Histolyticum (CCH) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/214 (0.00%)   0/206 (0.00%) 
Hide Serious Adverse Events
Collagenase Clostridium Histolyticum (CCH) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/214 (0.47%)   0/206 (0.00%) 
Metabolism and nutrition disorders     
Hypokalemia  1  1/214 (0.47%)  0/206 (0.00%) 
Nervous system disorders     
Syncope  1  1/214 (0.47%)  0/206 (0.00%) 
Vascular disorders     
Hypotension  1  1/214 (0.47%)  0/206 (0.00%) 
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Collagenase Clostridium Histolyticum (CCH) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   203/214 (94.86%)   64/206 (31.07%) 
General disorders     
Injection site bruising  1  193/214 (90.19%)  42/206 (20.39%) 
Injection site pain  1  127/214 (59.35%)  26/206 (12.62%) 
Injection site nodule  1  70/214 (32.71%)  2/206 (0.97%) 
Injection site pruritus  1  34/214 (15.89%)  3/206 (1.46%) 
Injection site erythema  1  28/214 (13.08%)  17/206 (8.25%) 
Injection site discolouration  1  21/214 (9.81%)  2/206 (0.97%) 
Injection site mass  1  15/214 (7.01%)  0/206 (0.00%) 
Injection site warmth  1  13/214 (6.07%)  0/206 (0.00%) 
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Saji Vijayan, MBBS
Organization: Endo Pharmaceuticals
Phone: 800-462-3636
EMail: ClinicalTrials@Endo.com
Layout table for additonal information
Responsible Party: Endo Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03446781    
Other Study ID Numbers: EN3835-303
First Submitted: February 4, 2018
First Posted: February 27, 2018
Results First Submitted: August 5, 2020
Results First Posted: October 8, 2020
Last Update Posted: October 8, 2020