Trial Outcomes & Findings for Effectiveness and Safety of EN3835 in the Treatment of EFP (Cellulite) in Women (NCT NCT03428750)

Last Updated: 2020-10-08

Results Overview

Number of 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 participant who missed one or two assessments of CR-PCSS and PR-PCSS at Day 71 was defined as a non-responder. A 2-level composite responder is defined as a participant with an 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

423 participants

Primary outcome timeframe

Day 71

Results posted on

2020-10-08

Participant Flow

Participant milestones

Participant milestones
Measure	Collagenase Clostridium Histolyticum (CCH) CCH 0.84 mg/Buttock 1.68 mg Total Dose	Placebo Placebo-control
Overall Study STARTED	210	213
Overall Study COMPLETED	186	192
Overall Study NOT COMPLETED	24	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Collagenase Clostridium Histolyticum (CCH) CCH 0.84 mg/Buttock 1.68 mg Total Dose	Placebo Placebo-control
Overall Study Withdrawal by Subject	11	10
Overall Study Lost to Follow-up	3	9
Overall Study Adverse Event	9	1
Overall Study Protocol Violation	1	0
Overall Study Administrative	0	1

Baseline Characteristics

Standard deviation for BMI group categories are based on total number of participants with non-missing BMI values.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Collagenase Clostridium Histolyticum (CCH) n=210 Participants CCH 0.84 mg/Buttock 1.68 mg Total Dose	Placebo n=213 Participants Placebo-control	Total n=423 Participants Total of all reporting groups
Age, Continuous	47.9 years STANDARD_DEVIATION 10.33 • n=210 Participants	45.8 years STANDARD_DEVIATION 9.84 • n=213 Participants	46.9 years STANDARD_DEVIATION 10.13 • n=423 Participants
Sex: Female, Male Female	210 Participants n=210 Participants	213 Participants n=213 Participants	423 Participants n=423 Participants
Sex: Female, Male Male	0 Participants n=210 Participants	0 Participants n=213 Participants	0 Participants n=423 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	31 Participants n=210 Participants	41 Participants n=213 Participants	72 Participants n=423 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	179 Participants n=210 Participants	172 Participants n=213 Participants	351 Participants n=423 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=210 Participants	0 Participants n=213 Participants	0 Participants n=423 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=210 Participants	2 Participants n=213 Participants	3 Participants n=423 Participants
Race (NIH/OMB) Asian	0 Participants n=210 Participants	2 Participants n=213 Participants	2 Participants n=423 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=210 Participants	1 Participants n=213 Participants	1 Participants n=423 Participants
Race (NIH/OMB) Black or African American	47 Participants n=210 Participants	43 Participants n=213 Participants	90 Participants n=423 Participants
Race (NIH/OMB) White	157 Participants n=210 Participants	161 Participants n=213 Participants	318 Participants n=423 Participants
Race (NIH/OMB) More than one race	3 Participants n=210 Participants	4 Participants n=213 Participants	7 Participants n=423 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=210 Participants	0 Participants n=213 Participants	2 Participants n=423 Participants
Body Mass Index (BMI)	31.04 kg/m^2 STANDARD_DEVIATION 7.358 • n=210 Participants • Standard deviation for BMI group categories are based on total number of participants with non-missing BMI values.	30.97 kg/m^2 STANDARD_DEVIATION 6.856 • n=212 Participants • Standard deviation for BMI group categories are based on total number of participants with non-missing BMI values.	31.00 kg/m^2 STANDARD_DEVIATION 7.102 • n=422 Participants • Standard deviation for BMI group categories are based on total number of participants with non-missing BMI values.
Skin Category (Fitzpatrick Scale) I (Pale White)	5 Participants n=210 Participants	4 Participants n=213 Participants	9 Participants n=423 Participants
Skin Category (Fitzpatrick Scale) II (Fair)	50 Participants n=210 Participants	48 Participants n=213 Participants	98 Participants n=423 Participants
Skin Category (Fitzpatrick Scale) III (Darker White)	69 Participants n=210 Participants	75 Participants n=213 Participants	144 Participants n=423 Participants
Skin Category (Fitzpatrick Scale) IV (Light Brown)	40 Participants n=210 Participants	35 Participants n=213 Participants	75 Participants n=423 Participants
Skin Category (Fitzpatrick Scale) V (Brown)	33 Participants n=210 Participants	27 Participants n=213 Participants	60 Participants n=423 Participants
Skin Category (Fitzpatrick Scale) VI (Dark Brown)	13 Participants n=210 Participants	24 Participants n=213 Participants	37 Participants n=423 Participants

PRIMARY outcome

Timeframe: Day 71

Population: 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.

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=210 Participants CCH 0.84 mg/Buttock	Placebo n=213 Participants Placebo-control	Day 22: CCH Day 22 for CCH Treated Group	Day 22: Placebo Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
2-level Composite Responders for the Target Buttock Yes: 2-Level Improvement	16 Participants	4 Participants	—	—	—	—	—	—	—	—
2-level Composite Responders for the Target Buttock No: 2-Level Improvement	194 Participants	209 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 71

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).

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=210 Participants CCH 0.84 mg/Buttock	Placebo n=213 Participants Placebo-control	Day 22: CCH Day 22 for CCH Treated Group	Day 22: Placebo Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
1-level PR-PCSS Responders of the Target Buttock Yes	114 Participants	77 Participants	—	—	—	—	—	—	—	—
1-level PR-PCSS Responders of the Target Buttock No	96 Participants	136 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 71

Improvement in cellulite severity of the Target Buttock from baseline of at least 2-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).

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=210 Participants CCH 0.84 mg/Buttock	Placebo n=213 Participants Placebo-control	Day 22: CCH Day 22 for CCH Treated Group	Day 22: Placebo Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
2-level PR-PCSS Responders of the Target Buttock Yes	51 Participants	26 Participants	—	—	—	—	—	—	—	—
2-level PR-PCSS Responders of the Target Buttock No	159 Participants	187 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 71

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).

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=210 Participants CCH 0.84 mg/Buttock	Placebo n=213 Participants Placebo-control	Day 22: CCH Day 22 for CCH Treated Group	Day 22: Placebo Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
1-level Composite Responders of the Target Buttock Yes	78 Participants	38 Participants	—	—	—	—	—	—	—	—
1-level Composite Responders of the Target Buttock No	132 Participants	175 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 71

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).

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=210 Participants CCH 0.84 mg/Buttock	Placebo n=213 Participants Placebo-control	Day 22: CCH Day 22 for CCH Treated Group	Day 22: Placebo Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
2-level Composite Responder of the Non-target Buttock Yes	16 Participants	2 Participants	—	—	—	—	—	—	—	—
2-level Composite Responder of the Non-target Buttock No	194 Participants	211 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 71

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.

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=210 Participants CCH 0.84 mg/Buttock	Placebo n=213 Participants Placebo-control	Day 22: CCH Day 22 for CCH Treated Group	Day 22: Placebo Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
1-level SSRS Responders	102 Participants	48 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 71 Days

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 was defined as a participant with a reduction in the PR-CIS total score of at least 12 from baseline at an evaluation time point. A negative change from baseline indicates an improvement in cellulite severity.

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=210 Participants CCH 0.84 mg/Buttock	Placebo n=213 Participants Placebo-control	Day 22: CCH Day 22 for CCH Treated Group	Day 22: Placebo Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
Change From Baseline in PR-CIS Total Score Change from Baseline	-10.9 score on a scale Standard Deviation 12.51	-5.9 score on a scale Standard Deviation 11.62	—	—	—	—	—	—	—	—
Change From Baseline in PR-CIS Total Score Baseline (Day 1)	51.1 score on a scale Standard Deviation 8.86	51.6 score on a scale Standard Deviation 9.77	—	—	—	—	—	—	—	—
Change From Baseline in PR-CIS Total Score Day 71	40.2 score on a scale Standard Deviation 13.27	45.7 score on a scale Standard Deviation 12.93	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 71

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 at least ≥ 1-level improvement (Improved, Much Improved or Very Much Improved) in S-GAIS assessment of the Target Buttock.

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=210 Participants CCH 0.84 mg/Buttock	Placebo n=213 Participants Placebo-control	Day 22: CCH Day 22 for CCH Treated Group	Day 22: Placebo Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
1-level S-GAIS Responders of Target Buttock	135 Participants	82 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 71

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 at least ≥ 2-level improvement (Much Improved or Very Much Improved) in S-GAIS assessment of the Target Buttock.

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=210 Participants CCH 0.84 mg/Buttock	Placebo n=213 Participants Placebo-control	Day 22: CCH Day 22 for CCH Treated Group	Day 22: Placebo Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
2-level S-GAIS Responders of Target Buttock	49 Participants	13 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 71

Population: 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 nontarget buttocks. All secondary and supportive efficacy evaluations were based on the mITT Population.

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 scale ratings range from "0" (None) to "4" (Severe).

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=201 Participants CCH 0.84 mg/Buttock	Placebo n=205 Participants Placebo-control	Day 22: CCH n=201 Participants Day 22 for CCH Treated Group	Day 22: Placebo n=205 Participants Day 22 for Placebo Group	Day 43: CCH n=201 Participants Day 43 for CCH Treated Group	Day 43: Placebo n=205 Participants Day 43 for Placebo Group	Day 71: CCH n=201 Participants Day 71 for CCH Treated Group	Day 71: Placebo n=205 Participants Day 71 for Placebo Group	Day 71: CCH (LOCF) n=201 Participants Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) n=205 Participants Day 71 for Placebo Group (Last observation carried forward)
PR-PCSS Rating for the Target and Non-target Buttock by Visit Target Buttock Rating · None (0)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants	2 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Target Buttock Rating · Almost None (1)	0 Participants	0 Participants	1 Participants	0 Participants	13 Participants	4 Participants	25 Participants	5 Participants	25 Participants	5 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Target Buttock Rating · Mild (2)	0 Participants	0 Participants	29 Participants	7 Participants	50 Participants	24 Participants	54 Participants	38 Participants	58 Participants	40 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Target Buttock Rating · Moderate (3)	84 Participants	82 Participants	79 Participants	95 Participants	75 Participants	95 Participants	65 Participants	77 Participants	72 Participants	81 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Target Buttock Rating · Severe (4)	117 Participants	123 Participants	78 Participants	100 Participants	50 Participants	71 Participants	40 Participants	67 Participants	46 Participants	77 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Nontarget Buttock Rating · None (0)	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	2 Participants	1 Participants	2 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Nontarget Buttock Rating · Almost None (1)	0 Participants	0 Participants	2 Participants	0 Participants	12 Participants	4 Participants	20 Participants	7 Participants	21 Participants	7 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Nontarget Buttock Rating · Mild (2)	0 Participants	0 Participants	27 Participants	9 Participants	50 Participants	33 Participants	55 Participants	34 Participants	59 Participants	35 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Nontarget Buttock Rating · Moderate (3)	81 Participants	83 Participants	81 Participants	89 Participants	80 Participants	82 Participants	63 Participants	88 Participants	70 Participants	93 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Nontarget Buttock Rating · Severe (4)	120 Participants	122 Participants	77 Participants	104 Participants	45 Participants	75 Participants	45 Participants	59 Participants	50 Participants	68 Participants

SECONDARY outcome

Timeframe: Day 71

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.

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=184 Participants CCH 0.84 mg/Buttock	Placebo n=190 Participants Placebo-control	Day 22: CCH n=195 Participants Day 22 for CCH Treated Group	Day 22: Placebo n=191 Participants Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
Subjects Satisfaction With Cellulite Treatment at Day 71 Very Satisfied (+2)	24 Participants	7 Participants	24 Participants	7 Participants	—	—	—	—	—	—
Subjects Satisfaction With Cellulite Treatment at Day 71 Satisfied (+1)	76 Participants	42 Participants	80 Participants	42 Participants	—	—	—	—	—	—
Subjects Satisfaction With Cellulite Treatment at Day 71 Neither Satisfied Nor Dissatisfied (0)	46 Participants	56 Participants	52 Participants	56 Participants	—	—	—	—	—	—
Subjects Satisfaction With Cellulite Treatment at Day 71 Dissatisfied (-1)	23 Participants	42 Participants	23 Participants	42 Participants	—	—	—	—	—	—
Subjects Satisfaction With Cellulite Treatment at Day 71 Very Dissatisfied (-2)	15 Participants	43 Participants	16 Participants	44 Participants	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 - Day 71

Population: 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.

Percent of participants that are seropositive. Percentages were based on the number of subjects who had immunogenicity lab samples analyzed at the visit.

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=209 Participants CCH 0.84 mg/Buttock	Placebo n=212 Participants Placebo-control	Day 22: CCH n=209 Participants Day 22 for CCH Treated Group	Day 22: Placebo n=212 Participants Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
Serum Antibody Positivity by Visit Day 1 · Seropositive	12 Participants	5 Participants	11 Participants	9 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 1 · Seronegative	197 Participants	207 Participants	198 Participants	203 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 22 · Seropositive	97 Participants	5 Participants	49 Participants	9 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 22 · Seronegative	90 Participants	195 Participants	138 Participants	191 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 43 · Seropositive	186 Participants	6 Participants	180 Participants	10 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 43 · Seronegative	2 Participants	188 Participants	8 Participants	184 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 71 · Seropositive	185 Participants	10 Participants	185 Participants	12 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 71 · Seronegative	0 Participants	182 Participants	0 Participants	180 Participants	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 - Day 71

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=209 Participants CCH 0.84 mg/Buttock	Placebo n=212 Participants Placebo-control	Day 22: CCH n=209 Participants Day 22 for CCH Treated Group	Day 22: Placebo n=212 Participants Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
Overall Antibody Titer Levels by Visit Day 1 positive	4.396 log 10 titer Standard Deviation 2.2644	3.682 log 10 titer Standard Deviation 2.2514	4.366 log 10 titer Standard Deviation 2.1658	2.478 log 10 titer Standard Deviation 1.6280	—	—	—	—	—	—
Overall Antibody Titer Levels by Visit Day 22 positive	2.561 log 10 titer Standard Deviation 1.7812	3.428 log 10 titer Standard Deviation 2.3377	2.599 log 10 titer Standard Deviation 2.1305	2.693 log 10 titer Standard Deviation 1.7244	—	—	—	—	—	—
Overall Antibody Titer Levels by Visit Day 43 positive	4.639 log 10 titer Standard Deviation 0.9961	2.597 log 10 titer Standard Deviation 1.5802	3.706 log 10 titer Standard Deviation 1.2138	2.052 log 10 titer Standard Deviation 1.3049	—	—	—	—	—	—
Overall Antibody Titer Levels by Visit Day 71 positive	6.011 log 10 titer Standard Deviation 0.6758	1.845 log 10 titer Standard Deviation 1.3931	5.266 log 10 titer Standard Deviation 0.7549	1.927 log 10 titer Standard Deviation 1.3274	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 71

Population: 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.

Q1 and Q4 are based on the ADA titer levels.

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=24 Participants CCH 0.84 mg/Buttock	Placebo n=24 Participants Placebo-control	Day 22: CCH n=48 Participants Day 22 for CCH Treated Group	Day 22: Placebo Day 22 for Placebo Group	Day 43: CCH Day 43 for CCH Treated Group	Day 43: Placebo Day 43 for Placebo Group	Day 71: CCH Day 71 for CCH Treated Group	Day 71: Placebo Day 71 for Placebo Group	Day 71: CCH (LOCF) Day 71 for CCH Treated Group (Last observation carried forward)	Day 71: Placebo (LOCF) Day 71 for Placebo Group (Last observation carried forward)
Presence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles Neutralizing AUX-I Antibody · Negative	16 Participants	0 Participants	16 Participants	—	—	—	—	—	—	—
Presence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles Neutralizing AUX-I Antibody · Positive	8 Participants	24 Participants	32 Participants	—	—	—	—	—	—	—
Presence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles Neutralizing AUX-II Antibody · Negative	10 Participants	0 Participants	10 Participants	—	—	—	—	—	—	—
Presence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles Neutralizing AUX-II Antibody · Positive	13 Participants	23 Participants	36 Participants	—	—	—	—	—	—	—

Adverse Events

Collagenase Clostridium Histolyticum (CCH)

Serious events: 0 serious events

Other events: 166 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Collagenase Clostridium Histolyticum (CCH) n=210 participants at risk CCH 0.84 mg/Buttock 1.68 mg Total Dose	Placebo n=213 participants at risk Placebo-control
Gastrointestinal disorders Colitis ischaemic	0.00% 0/210 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.	0.47% 1/213 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.

Other adverse events

Other adverse events
Measure	Collagenase Clostridium Histolyticum (CCH) n=210 participants at risk CCH 0.84 mg/Buttock 1.68 mg Total Dose	Placebo n=213 participants at risk Placebo-control
General disorders Injection site pain	36.2% 76/210 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.	5.2% 11/213 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.
General disorders Injection site bruising	65.2% 137/210 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.	19.7% 42/213 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.
General disorders Injection stie nodule	18.1% 38/210 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.	0.00% 0/213 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.
General disorders Injection site pruritus	13.8% 29/210 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.	0.47% 1/213 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.
General disorders Injection site haemorrhage	11.9% 25/210 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.	2.3% 5/213 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.
General disorders Injection site mass	8.6% 18/210 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.	0.47% 1/213 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.
General disorders Injection site swelling	7.1% 15/210 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.	0.00% 0/213 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.
General disorders Injection site discolouration	5.7% 12/210 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.	0.00% 0/213 • All (serious and nonserious) AEs, from Day 1 to Day 71 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.

Additional Information

Saji Vijayan, MBBS

Endo Pharmaceuticals

Phone: 800-462-3636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place