Trial Outcomes & Findings for Safety and Effectiveness of EN3835 in the Treatment of EFP in Women (NCT NCT03329989)

NCT ID: NCT03329989

Last Updated: 2020-12-29

Results Overview

Percentage of responders defined as participants with an improvement in cellulite severity from baseline of at least 2-levels of severity of at least one buttock (left or right) on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) with ratings ranging from "0" (None) to "4" (Severe). A 2-level responder is a participant with a reduction in severity of at least 2-levels from Baseline at that particular visit. Number of participants analyzed is determined by observed participants at each visit.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

158 participants

Primary outcome timeframe

Day 22, 43, 90, and 180

Results posted on

2020-12-29

Participant Flow

Participant milestones

Participant milestones
Measure
Collagenase Clostridium Histolyticum (CCH)
12 injections of CCH (Collagenase Clostridium Histolyticum) were administered per treatment area at each treatment visit during 3 visits.
Overall Study
STARTED
158
Overall Study
COMPLETED
135
Overall Study
NOT COMPLETED
23

Reasons for withdrawal

Reasons for withdrawal
Measure
Collagenase Clostridium Histolyticum (CCH)
12 injections of CCH (Collagenase Clostridium Histolyticum) were administered per treatment area at each treatment visit during 3 visits.
Overall Study
Withdrawal by Subject
9
Overall Study
Lost to Follow-up
8
Overall Study
Adverse Event
5
Overall Study
Protocol Violation
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Collagenase Clostridium Histolyticum (CCH)
n=158 Participants
12 injections of CCH (Collagenase Clostridium Histolyticum) were administered per treatment area at each treatment visit during 3 visits.
Age, Continuous
44.8 years
STANDARD_DEVIATION 10.41 • n=5 Participants
Sex: Female, Male
Female
158 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
44 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
114 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
2 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
17 Participants
n=5 Participants
Race (NIH/OMB)
White
135 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
4 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Body Mass Index (BMI)
26.74 kg/m^2
STANDARD_DEVIATION 5.259 • n=5 Participants
Skin Category (Fitzpatrick Scale)
I (Pale White)
3 Participants
n=5 Participants
Skin Category (Fitzpatrick Scale)
II (Fair)
34 Participants
n=5 Participants
Skin Category (Fitzpatrick Scale)
III (Darker White)
53 Participants
n=5 Participants
Skin Category (Fitzpatrick Scale)
IV (Light Brown)
48 Participants
n=5 Participants
Skin Category (Fitzpatrick Scale)
V (Brown)
10 Participants
n=5 Participants
Skin Category (Fitzpatrick Scale)
VI (Dark Brown)
10 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Day 22, 43, 90, and 180

Population: Effectiveness Population

Percentage of responders defined as participants with an improvement in cellulite severity from baseline of at least 2-levels of severity of at least one buttock (left or right) on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) with ratings ranging from "0" (None) to "4" (Severe). A 2-level responder is a participant with a reduction in severity of at least 2-levels from Baseline at that particular visit. Number of participants analyzed is determined by observed participants at each visit.

Outcome measures

Outcome measures
Measure
Collagenase Clostridium Histolyticum (CCH)
n=144 Participants
12 injections of CCH (Collagenase Clostridium Histolyticum) were administered per treatment area at each treatment visit during 3 visits.
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 2-level Responders
At Least One of two areas (Left & Right): Day 22 · Yes
6 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 2-level Responders
At Least One of two areas (Left & Right): Day 22 · No
131 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 2-level Responders
At Least One of two areas (Left & Right): Day 43 · Yes
8 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 2-level Responders
At Least One of two areas (Left & Right): Day 43 · No
125 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 2-level Responders
At Least One of two areas (Left & Right): Day 90 · Yes
17 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 2-level Responders
At Least One of two areas (Left & Right): Day 90 · No
110 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 2-level Responders
At Least One of two areas (Left & Right): Day 180 · Yes
20 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 2-level Responders
At Least One of two areas (Left & Right): Day 180 · No
111 Participants

SECONDARY outcome

Timeframe: Day 22, 43, 90, and 180

Population: Effectiveness Population

Percentage of responders defined as participants with an improvement in cellulite severity from baseline of at least 1-level of severity of at least one buttock (left or right) on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) with ratings ranging from "0" (None) to "4" (Severe). A 1-level responder is a participant with a reduction in severity of at least 1-level from Baseline at that particular visit. Percentages are based on the observed counts. Number of participants analyzed is determined by observed participants at each visit.

Outcome measures

Outcome measures
Measure
Collagenase Clostridium Histolyticum (CCH)
n=144 Participants
12 injections of CCH (Collagenase Clostridium Histolyticum) were administered per treatment area at each treatment visit during 3 visits.
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 1-level Responders
At Least One of Two Areas (Left & Right): Day 22 · Yes
55 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 1-level Responders
At Least One of Two Areas (Left & Right): Day 22 · No
82 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 1-level Responders
At Least One of Two Areas (Left & Right): Day 43 · Yes
87 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 1-level Responders
At Least One of Two Areas (Left & Right): Day 43 · No
46 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 1-level Responders
At Least One of Two Areas (Left & Right): Day 90 · Yes
96 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 1-level Responders
At Least One of Two Areas (Left & Right): Day 90 · No
31 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 1-level Responders
At Least One of Two Areas (Left & Right): Day 180 · Yes
90 Participants
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 1-level Responders
At Least One of Two Areas (Left & Right): Day 180 · No
41 Participants

SECONDARY outcome

Timeframe: Day 180

Population: Overall number of participants analyzed is the number participants in effectiveness population at Day 180.

At Day 180, participants rated their satisfaction with cellulite treatment using the 5-point subject satisfaction scale. Ratings range from Very Satisfied with Treatment (2), Satisfied with Treatment (1), Neither Dissatisfied nor Satisfied with Treatment (0), Dissatisfied with Treatment (-1), and Very Dissatisfied with Treatment (-2). Percentages are based on the observed counts.

Outcome measures

Outcome measures
Measure
Collagenase Clostridium Histolyticum (CCH)
n=130 Participants
12 injections of CCH (Collagenase Clostridium Histolyticum) were administered per treatment area at each treatment visit during 3 visits.
Subject Satisfaction With Cellulite Treatment Assessment at End of Study
Very Satisfied with Treatment (2)
25 Participants
Subject Satisfaction With Cellulite Treatment Assessment at End of Study
Satisfied with Treatment (1)
48 Participants
Subject Satisfaction With Cellulite Treatment Assessment at End of Study
Neither Dissatisfied nor Satisfied with Treatment
32 Participants
Subject Satisfaction With Cellulite Treatment Assessment at End of Study
Dissatisfied with Treatment (-1)
12 Participants
Subject Satisfaction With Cellulite Treatment Assessment at End of Study
Very Dissatisfied with Treatment (-2)
13 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 180

Population: Safety Population

Percent of participants that are seropositive. Descriptive statistics were based on log10 transformation of titer levels. Percentages were based on the number of subjects who had immunogenicity lab samples drawn at the visit. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.

Outcome measures

Outcome measures
Measure
Collagenase Clostridium Histolyticum (CCH)
n=158 Participants
12 injections of CCH (Collagenase Clostridium Histolyticum) were administered per treatment area at each treatment visit during 3 visits.
Overall Anti-AUX-I Serum Antibody by Visit
Anti-AUX-I: Day 1 · Seropositive
4 Participants
Overall Anti-AUX-I Serum Antibody by Visit
Anti-AUX-I: Day 1 · Seronegative
152 Participants
Overall Anti-AUX-I Serum Antibody by Visit
Anti-AUX-I: Day 22 · Seropositive
104 Participants
Overall Anti-AUX-I Serum Antibody by Visit
Anti-AUX-I: Day 22 · Seronegative
43 Participants
Overall Anti-AUX-I Serum Antibody by Visit
Anti-AUX-I: Day 43 · Seropositive
141 Participants
Overall Anti-AUX-I Serum Antibody by Visit
Anti-AUX-I: Day 43 · Seronegative
2 Participants
Overall Anti-AUX-I Serum Antibody by Visit
Anti-AUX-I: Day 90 · Seropositive
134 Participants
Overall Anti-AUX-I Serum Antibody by Visit
Anti-AUX-I: Day 90 · Seronegative
0 Participants
Overall Anti-AUX-I Serum Antibody by Visit
Anti-AUX-I: Day 180 · Seropositive
134 Participants
Overall Anti-AUX-I Serum Antibody by Visit
Anti-AUX-I: Day 180 · Seronegative
1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 180

Population: Safety Population

Descriptive statistics were based on log10 transformation of titer levels. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.

Outcome measures

Outcome measures
Measure
Collagenase Clostridium Histolyticum (CCH)
n=158 Participants
12 injections of CCH (Collagenase Clostridium Histolyticum) were administered per treatment area at each treatment visit during 3 visits.
Overall Anti-AUX-I Antibody Log Titer Levels by Visit
Anti-AUX-I: Day 1 positive
2.046 log 10 titer
Standard Deviation 1.012
Overall Anti-AUX-I Antibody Log Titer Levels by Visit
Anti-AUX-I: Day 22 positive
2.268 log 10 titer
Standard Deviation 1.076
Overall Anti-AUX-I Antibody Log Titer Levels by Visit
Anti-AUX-I: Day 43 positive
4.681 log 10 titer
Standard Deviation 0.924
Overall Anti-AUX-I Antibody Log Titer Levels by Visit
Anti-AUX-I: Day 90 positive
5.937 log 10 titer
Standard Deviation 0.686
Overall Anti-AUX-I Antibody Log Titer Levels by Visit
Anti-AUX-I: Day 180 positive
5.556 log 10 titer
Standard Deviation 0.981

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 180

Population: Safety Population

Percent of participants that are seropositive. Descriptive statistics were based on log10 transformation of titer levels. Percentages were based on the number of subjects who had immunogenicity lab samples drawn at the visit. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.

Outcome measures

Outcome measures
Measure
Collagenase Clostridium Histolyticum (CCH)
n=158 Participants
12 injections of CCH (Collagenase Clostridium Histolyticum) were administered per treatment area at each treatment visit during 3 visits.
Overall Anti-AUX-II Serum Antibody by Visit
Anti-AUX-I: Day 1 · Seropositive
6 Participants
Overall Anti-AUX-II Serum Antibody by Visit
Anti-AUX-I: Day 1 · Seronegative
150 Participants
Overall Anti-AUX-II Serum Antibody by Visit
Anti-AUX-I: Day 22 · Seropositive
50 Participants
Overall Anti-AUX-II Serum Antibody by Visit
Anti-AUX-I: Day 22 · Seronegative
98 Participants
Overall Anti-AUX-II Serum Antibody by Visit
Anti-AUX-I: Day 43 · Seropositive
138 Participants
Overall Anti-AUX-II Serum Antibody by Visit
Anti-AUX-I: Day 43 · Seronegative
5 Participants
Overall Anti-AUX-II Serum Antibody by Visit
Anti-AUX-I: Day 90 · Seropositive
131 Participants
Overall Anti-AUX-II Serum Antibody by Visit
Anti-AUX-I: Day 90 · Seronegative
0 Participants
Overall Anti-AUX-II Serum Antibody by Visit
Anti-AUX-I: Day 180 · Seropositive
130 Participants
Overall Anti-AUX-II Serum Antibody by Visit
Anti-AUX-I: Day 180 · Seronegative
5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 180

Population: Safety Population

Descriptive statistics were based on log10 transformation of titer levels. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.

Outcome measures

Outcome measures
Measure
Collagenase Clostridium Histolyticum (CCH)
n=158 Participants
12 injections of CCH (Collagenase Clostridium Histolyticum) were administered per treatment area at each treatment visit during 3 visits.
Overall Anti-AUX-II Antibody Log Titer Levels by Visit
Anti-AUX-II: Day 1 positive
1.607 log 10 titer
Standard Deviation 0.947
Overall Anti-AUX-II Antibody Log Titer Levels by Visit
Anti-AUX-II: Day 22 positive
1.942 log 10 titer
Standard Deviation 1.068
Overall Anti-AUX-II Antibody Log Titer Levels by Visit
Anti-AUX-II: Day 43 positive
3.641 log 10 titer
Standard Deviation 1.068
Overall Anti-AUX-II Antibody Log Titer Levels by Visit
Anti-AUX-II: Day 90 positive
5.255 log 10 titer
Standard Deviation 0.809
Overall Anti-AUX-II Antibody Log Titer Levels by Visit
Anti-AUX-II: Day 180 positive
5.141 log 10 titer
Standard Deviation 0.913

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 180

Population: Safety Population

A subset of all CCH Treated participants who had positive binding antibody titer levels were tested for the presence or absence of Neutralizing Antibodies. Overall Number of Participants Analyzed is determined by the number of participants in the highest and lowest quartiles at Day 90 (Q1 and Q4) of seropositive participants at each of two visits (Day 90 and Day 180).

Outcome measures

Outcome measures
Measure
Collagenase Clostridium Histolyticum (CCH)
n=34 Participants
12 injections of CCH (Collagenase Clostridium Histolyticum) were administered per treatment area at each treatment visit during 3 visits.
Anti-AUX-I Neutralizing Antibodies by Visit
anti-AUX-I Neutralizing Antibody: Day 1 · Positive
0 Participants
Anti-AUX-I Neutralizing Antibodies by Visit
anti-AUX-I Neutralizing Antibody: Day 1 · Negative
1 Participants
Anti-AUX-I Neutralizing Antibodies by Visit
anti-AUX-I Neutralizing Antibody: Day 90 · Positive
26 Participants
Anti-AUX-I Neutralizing Antibodies by Visit
anti-AUX-I Neutralizing Antibody: Day 90 · Negative
8 Participants
Anti-AUX-I Neutralizing Antibodies by Visit
anti-AUX-I Neutralizing Antibody: Day 180 · Positive
19 Participants
Anti-AUX-I Neutralizing Antibodies by Visit
anti-AUX-I Neutralizing Antibody: Day 180 · Negative
14 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 180

Population: Safety Population

A subset of all CCH Treated participants who had positive binding antibody titer levels were tested for the presence or absence of Neutralizing Antibodies. Overall Number of Participants Analyzed is determined by the number of participants in the study. Number of Participants Analyzed is determined by observed participants that had a seropositive sample at each visit and the antibody level at Day 71 in Q1 and Q4.

Outcome measures

Outcome measures
Measure
Collagenase Clostridium Histolyticum (CCH)
n=32 Participants
12 injections of CCH (Collagenase Clostridium Histolyticum) were administered per treatment area at each treatment visit during 3 visits.
Anti-AUX-II Neutralizing Antibodies by Visit
anti-AUX-II Neutralizing Antibodies: Day 1 · Positive
1 Participants
Anti-AUX-II Neutralizing Antibodies by Visit
anti-AUX-II Neutralizing Antibodies: Day 1 · Negative
0 Participants
Anti-AUX-II Neutralizing Antibodies by Visit
anti-AUX-II Neutralizing Antibodies: Day 90 · Positive
24 Participants
Anti-AUX-II Neutralizing Antibodies by Visit
anti-AUX-II Neutralizing Antibodies: Day 90 · Negative
8 Participants
Anti-AUX-II Neutralizing Antibodies by Visit
anti-AUX-II Neutralizing Antibodies: Day 180 · Positive
20 Participants
Anti-AUX-II Neutralizing Antibodies by Visit
anti-AUX-II Neutralizing Antibodies: Day 180 · Negative
11 Participants

Adverse Events

Collagenase Clostridium Histolyticum (CCH)

Serious events: 1 serious events
Other events: 158 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Collagenase Clostridium Histolyticum (CCH)
n=158 participants at risk
EN3835 0.84mg (Collagenase Clostridium Histolyticum) Collagenase Clostridium Histolyticum: During 3 treatment visits 12 injections is given per treatment area
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
0.63%
1/158 • All (serious and non-serious) AEs, from Day 1 up to Day 180
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=158 participants at risk
EN3835 0.84mg (Collagenase Clostridium Histolyticum) Collagenase Clostridium Histolyticum: During 3 treatment visits 12 injections is given per treatment area
General disorders
Injection site bruising
86.1%
136/158 • All (serious and non-serious) AEs, from Day 1 up to Day 180
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
48.1%
76/158 • All (serious and non-serious) AEs, from Day 1 up to Day 180
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
22.2%
35/158 • All (serious and non-serious) AEs, from Day 1 up to Day 180
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
17.1%
27/158 • All (serious and non-serious) AEs, from Day 1 up to Day 180
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
16.5%
26/158 • All (serious and non-serious) AEs, from Day 1 up to Day 180
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
14.6%
23/158 • All (serious and non-serious) AEs, from Day 1 up to Day 180
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
11.4%
18/158 • All (serious and non-serious) AEs, from Day 1 up to Day 180
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
10.8%
17/158 • All (serious and non-serious) AEs, from Day 1 up to Day 180
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
6.3%
10/158 • All (serious and non-serious) AEs, from Day 1 up to Day 180
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.
Skin and subcutaneous tissue disorders
Hemosiderin stain
5.1%
8/158 • All (serious and non-serious) AEs, from Day 1 up to Day 180
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

Results disclosure agreements

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