Trial Outcomes & Findings for Effectiveness and Safety of EN3835 in the Treatment of Cellulite in Women (NCT NCT03446781)

Last Updated: 2020-10-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

422 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	214	208
Overall Study COMPLETED	186	191
Overall Study NOT COMPLETED	28	17

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 Lost to Follow-up	11	5
Overall Study Withdrawal by Subject	9	7
Overall Study Adverse Event	8	2
Overall Study Protocol Violation	0	3

Baseline Characteristics

Effectiveness and Safety of EN3835 in the Treatment of Cellulite in Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Collagenase Clostridium Histolyticum (CCH) n=214 Participants CCH 0.84 mg/Buttock 1.68 mg Total Dose	Placebo n=206 Participants Placebo-control	Total n=420 Participants Total of all reporting groups
Age, Continuous	47.7 years STANDARD_DEVIATION 10.62 • n=5 Participants	45.7 years STANDARD_DEVIATION 11.16 • n=7 Participants	46.7 years STANDARD_DEVIATION 10.92 • n=5 Participants
Sex: Female, Male Female	214 Participants n=5 Participants	206 Participants n=7 Participants	420 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	46 Participants n=5 Participants	58 Participants n=7 Participants	104 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	168 Participants n=5 Participants	148 Participants n=7 Participants	316 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	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	29 Participants n=5 Participants	32 Participants n=7 Participants	61 Participants n=5 Participants
Race (NIH/OMB) White	179 Participants n=5 Participants	164 Participants n=7 Participants	343 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Body Mass Index (BMI)	30.52 kg/m^2 STANDARD_DEVIATION 6.184 • n=5 Participants	31.14 kg/m^2 STANDARD_DEVIATION 7.567 • n=7 Participants	30.82 kg/m^2 STANDARD_DEVIATION 6.896 • n=5 Participants
Skin Category (Fitzpatrick Scale) I (Pale White)	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Skin Category (Fitzpatrick Scale) II (Fair)	74 Participants n=5 Participants	54 Participants n=7 Participants	128 Participants n=5 Participants
Skin Category (Fitzpatrick Scale) III (Darker White)	50 Participants n=5 Participants	64 Participants n=7 Participants	114 Participants n=5 Participants
Skin Category (Fitzpatrick Scale) IV (Light Brown)	53 Participants n=5 Participants	47 Participants n=7 Participants	100 Participants n=5 Participants
Skin Category (Fitzpatrick Scale) V (Brown)	15 Participants n=5 Participants	18 Participants n=7 Participants	33 Participants n=5 Participants
Skin Category (Fitzpatrick Scale) VI (Dark Brown)	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 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=214 Participants CCH 0.84 mg/Buttock	Placebo n=206 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	12 Participants	1 Participants	—	—	—	—	—	—	—	—
2-level Composite Responders for the Target Buttock No	202 Participants	205 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=214 Participants CCH 0.84 mg/Buttock	Placebo n=206 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	124 Participants	61 Participants	—	—	—	—	—	—	—	—
1-level PR-PCSS Responders of the Target Buttock No	90 Participants	145 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 71

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).

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=214 Participants CCH 0.84 mg/Buttock	Placebo n=206 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	45 Participants	12 Participants	—	—	—	—	—	—	—	—
2-level PR-PCSS Responders of the Target Buttock No	169 Participants	194 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=214 Participants CCH 0.84 mg/Buttock	Placebo n=206 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	89 Participants	23 Participants	—	—	—	—	—	—	—	—
1-level Composite Responders of the Target Buttock No	125 Participants	183 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=214 Participants CCH 0.84 mg/Buttock	Placebo n=206 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 of the Non-target Buttock No	201 Participants	202 Participants	—	—	—	—	—	—	—	—
2-level Composite Responders of the Non-target Buttock Yes	13 Participants	4 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=214 Participants CCH 0.84 mg/Buttock	Placebo n=206 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	90 Participants	31 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 71

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.

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=214 Participants CCH 0.84 mg/Buttock	Placebo n=206 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 Baseline (Day 1)	52.4 score on a scale Standard Deviation 8.01	51.6 score on a scale Standard Deviation 9.40	—	—	—	—	—	—	—	—
Change From Baseline in PR-CIS Total Score Day 71	40.9 score on a scale Standard Deviation 13.57	45.1 score on a scale Standard Deviation 12.65	—	—	—	—	—	—	—	—
Change From Baseline in PR-CIS Total Score Change from Baseline	-11.5 score on a scale Standard Deviation 12.74	-6.5 score on a scale Standard Deviation 11.74	—	—	—	—	—	—	—	—

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

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=214 Participants CCH 0.84 mg/Buttock	Placebo n=206 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	126 Participants	46 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 ≥ 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=214 Participants CCH 0.84 mg/Buttock	Placebo n=206 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	38 Participants	9 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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 non-target 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 ratings range from "0" (None) to "4" (Severe).

Outcome measures

Outcome measures
Measure	Collagenase Clostridium Histolyticum (CCH) n=209 Participants CCH 0.84 mg/Buttock	Placebo n=201 Participants Placebo-control	Day 22: CCH n=209 Participants Day 22 for CCH Treated Group	Day 22: Placebo n=201 Participants Day 22 for Placebo Group	Day 43: CCH n=209 Participants Day 43 for CCH Treated Group	Day 43: Placebo n=201 Participants Day 43 for Placebo Group	Day 71: CCH n=209 Participants Day 71 for CCH Treated Group	Day 71: Placebo n=201 Participants Day 71 for Placebo Group	Day 71: CCH (LOCF) n=209 Participants Day 71 for CCH Treated Group (Last Observation Carried Forward)	Day 71: Placebo (LOCF) n=201 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	1 Participants	0 Participants	0 Participants	3 Participants	0 Participants	3 Participants	0 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	1 Participants	17 Participants	3 Participants	19 Participants	2 Participants	19 Participants	2 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Target Buttock Rating · Mild (2)	0 Participants	0 Participants	45 Participants	17 Participants	61 Participants	26 Participants	61 Participants	32 Participants	64 Participants	32 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Target Buttock Rating · Moderate (3)	89 Participants	82 Participants	78 Participants	79 Participants	67 Participants	85 Participants	65 Participants	76 Participants	76 Participants	81 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Target Buttock Rating · Severe (4)	120 Participants	119 Participants	73 Participants	101 Participants	41 Participants	77 Participants	38 Participants	81 Participants	47 Participants	86 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Non-target Buttock Rating · None (0)	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Non-target Buttock Rating · Almost None (1)	0 Participants	0 Participants	3 Participants	0 Participants	17 Participants	4 Participants	21 Participants	3 Participants	21 Participants	3 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Non-target Buttock Rating · Mild (2)	0 Participants	0 Participants	38 Participants	19 Participants	55 Participants	24 Participants	58 Participants	32 Participants	64 Participants	34 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Non-target Buttock Rating · Moderate (3)	96 Participants	71 Participants	82 Participants	71 Participants	67 Participants	86 Participants	66 Participants	72 Participants	74 Participants	75 Participants
PR-PCSS Rating for the Target and Non-target Buttock by Visit Non-target Buttock Rating · Severe (4)	113 Participants	130 Participants	74 Participants	108 Participants	47 Participants	77 Participants	40 Participants	84 Participants	49 Participants	89 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=186 Participants CCH 0.84 mg/Buttock	Placebo n=191 Participants Placebo-control	Day 22: CCH n=198 Participants Day 22 for CCH Treated Group	Day 22: Placebo n=195 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 Very Satisfied (+2)	15 Participants	4 Participants	15 Participants	4 Participants	—	—	—	—	—	—
Subjects Satisfaction With Cellulite Treatment Satisfied (+1)	72 Participants	22 Participants	74 Participants	22 Participants	—	—	—	—	—	—
Subjects Satisfaction With Cellulite Treatment Neither Satisfied Nor Dissatisfied (0)	60 Participants	73 Participants	64 Participants	75 Participants	—	—	—	—	—	—
Subjects Satisfaction With Cellulite Treatment Dissatisfied (-1)	24 Participants	47 Participants	29 Participants	48 Participants	—	—	—	—	—	—
Subjects Satisfaction With Cellulite Treatment Very Dissatisfied (-2)	15 Participants	45 Participants	16 Participants	46 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=214 Participants CCH 0.84 mg/Buttock	Placebo n=206 Participants Placebo-control	Day 22: CCH n=214 Participants Day 22 for CCH Treated Group	Day 22: Placebo n=206 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	6 Participants	2 Participants	3 Participants	6 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 71 · Seronegative	0 Participants	182 Participants	1 Participants	181 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 1 · Seronegative	208 Participants	204 Participants	211 Participants	200 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 22 · Seropositive	106 Participants	1 Participants	52 Participants	7 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 22 · Seronegative	90 Participants	198 Participants	144 Participants	192 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 43 · Seropositive	183 Participants	4 Participants	183 Participants	7 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 43 · Seronegative	3 Participants	186 Participants	3 Participants	183 Participants	—	—	—	—	—	—
Serum Antibody Positivity by Visit Day 71 · Seropositive	186 Participants	8 Participants	185 Participants	9 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=214 Participants CCH 0.84 mg/Buttock	Placebo n=206 Participants Placebo-control	Day 22: CCH n=214 Participants Day 22 for CCH Treated Group	Day 22: Placebo n=206 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	2.235 log 10 titer Standard Deviation 1.7365	1.000 log 10 titer Standard Deviation 0.0000	3.212 log 10 titer Standard Deviation 0.8056	1.365 log 10 titer Standard Deviation 0.3834	—	—	—	—	—	—
Overall Antibody Titer Levels by Visit Day 22 positive	2.331 log 10 titer Standard Deviation 1.2566	3.504 log 10 titer	1.912 log 10 titer Standard Deviation 1.2718	1.387 log 10 titer Standard Deviation 0.4788	—	—	—	—	—	—
Overall Antibody Titer Levels by Visit Day 43 positive	4.602 log 10 titer Standard Deviation 0.8721	2.539 log 10 titer Standard Deviation 1.1462	3.680 log 10 titer Standard Deviation 1.0617	1.302 log 10 titer Standard Deviation 0.4596	—	—	—	—	—	—
Overall Antibody Titer Levels by Visit Day 71 positive	5.898 log 10 titer Standard Deviation 0.7131	2.039 log 10 titer Standard Deviation 1.2854	5.255 log 10 titer Standard Deviation 0.7142	1.572 log 10 titer Standard Deviation 0.7895	—	—	—	—	—	—

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	12 Participants	3 Participants	15 Participants	—	—	—	—	—	—	—
Presence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles Neutralizing AUX-I Antibody · Positive	12 Participants	21 Participants	33 Participants	—	—	—	—	—	—	—
Presence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles Neutralizing AUX-II Antibody · Negative	5 Participants	1 Participants	6 Participants	—	—	—	—	—	—	—
Presence of Neutralizing Antibody (Seropositivity) at Day 71 (LOCF) by Antidrug Antibody Log Titer Quartiles Neutralizing AUX-II Antibody · Positive	19 Participants	23 Participants	42 Participants	—	—	—	—	—	—	—

Adverse Events

Collagenase Clostridium Histolyticum (CCH)

Serious events: 1 serious events

Other events: 203 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Collagenase Clostridium Histolyticum (CCH) n=214 participants at risk CCH 0.84 mg/Buttock 1.68 mg Total Dose	Placebo n=206 participants at risk Placebo-control
Nervous system disorders Syncope	0.47% 1/214 • 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% 0/206 • 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.
Vascular disorders Hypotension	0.47% 1/214 • 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% 0/206 • 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.
Metabolism and nutrition disorders Hypokalemia	0.47% 1/214 • 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% 0/206 • 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=214 participants at risk CCH 0.84 mg/Buttock 1.68 mg Total Dose	Placebo n=206 participants at risk Placebo-control
General disorders Injection site bruising	90.2% 193/214 • 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.	20.4% 42/206 • 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 pain	59.3% 127/214 • 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.	12.6% 26/206 • 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 nodule	32.7% 70/214 • 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.	0.97% 2/206 • 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	15.9% 34/214 • 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.	1.5% 3/206 • 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 erythema	13.1% 28/214 • 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.	8.3% 17/206 • 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	9.8% 21/214 • 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.	0.97% 2/206 • 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	7.0% 15/214 • 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% 0/206 • 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 warmth	6.1% 13/214 • 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% 0/206 • 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