Edematous Fibrosclerotic Panniculopathy, Cellulite
Conditions
Brief summary
A Phase 3b, Open-Label Extension Study to evaluate safety and how long response of EN3835 (Collagenase Clostridium Histolyticum \[CCH\]-aaes) lasts in the treatment of Cellulite.
Detailed description
This study included participants who completed EN3835-302 (NCT03428750) or EN3835-303 (NCT03446781) double-blind parent studies. The first part of this study consisted of an observational period conducted in a blinded fashion and where no treatments were administered between Day 71 of the parent studies and Day 180 in this Open-label extension study. Once these participants were unblinded at Day 180, only participants who received active CCH-aaes in the parent studies remained in this study and those who received placebo in the parent studies were not eligible to continue in the Open-label study. Assessments made at the Day 71/(End of Study \[EOS\]) visit of the parent studies served as initial screening assessments for this study. In the Open-label Phase of the study, all participants who qualified for, and opted for, retreatment were administered CCH-aaes at 3 treatment sessions at 21-day intervals.
Interventions
BIOLOGICALCCH-aaes
Administered to participants who qualified for, and opted for, retreatment.
OTHERObservation
No treatment administered during 180 days of observation.
Sponsors
Endo Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Investigators, participants, and site personnel were blinded to the treatment administered in the EN3835-302/303 parent studies until all Day 180 visit assessments were completed. CCH-aaes retreatment in this study was provided in an open-label manner.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria All Participants (Through Day 180): 1. Voluntarily sign and date an informed consent agreement 2. Have participated in and completed the double-blind Phase 3 study EN3835-302 or EN3835-303 3. Be willing to apply sunscreen to the buttocks before each exposure to the sun and/or tanning booths while participating in the study 4. Be judged to be in good health 5. Be willing and able to cooperate with the requirements of the study 6. Be able to read, complete and understand the participant reported outcomes rating instruments in English. Key Inclusion Criteria for Participants Eligible for Retreatment: 1\. Have a negative pregnancy test and using a stable and effective contraception method. Key
Exclusion criteria
All Participants (Through Day 180): 1. Intends to or has used any of the local applications/therapies/injections/procedures that restricts study participation 2. Intends to use tanning spray or tanning booths during this period 3. Has received or intends to receive an investigational drug or treatment, other than the treatment received in study EN3835-302/303 during this period 4. Any other condition(s) that, in the Investigator's opinion, might indicate the participant to be unsuitable for the study Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to Day 1080 | An adverse event (AE) was any unfavorable or unintended change in body structure (signs), body function (symptoms), laboratory result, or worsening of a pre-existing condition associated temporally with the use of the study medication whether or not considered related to the study medication. TEAEs were defined as any AEs with a start date equal to or after the date of the first injection. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Percentage of Participants Who Were Seropositive for Anti-Drug Antibodies (ADAs) After CCH-aaes Treatment | From Day 180 (Open-label Phase) up to Day 1080 | Serum samples were analyzed for ADAs. The percentage of participants who developed ADAs (seropositive results) during the Open-label Phase of the study are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to 2-Level Reduction of Response in Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) | From Day 180 (Open-label Observation Phase) up to Day 1080 | CR-PCSS and PR-PCSS assess improvement in cellulite severity using a 5-level scale ranging from 0 (None) to 4 (Severe). Time to reduction of response (days) was defined as the number of days from Screening assessment of composite improvement in cellulite severity in PR-PCSS and CR-PCSS to the time at which a 2-level composite worsening of response was observed for the first time. |
| Time to 1-Level Reduction of Response in CR-PCSS and PR-PCSS | From Day 180 (Open-label Observation Phase) up to Day 1080 | CR-PCSS and PR-PCSS assess improvement in cellulite severity using a 5-level scale ranging from 0 (None) to 4 (Severe). Time to reduction of response (days) was defined as the number of days from Screening assessment of composite improvement in cellulite severity in CR-PCSS and PR-PCSS to the time at which 1-level composite worsening of response was observed for the first time. |
| Time to Complete Loss of Response in CR-PCSS and PR-PCSS | From Day 180 (Open-label Observation Phase) up to Day 1080 | CR-PCSS and PR-PCSS assess improvement in cellulite severity using a 5-level scale ranging from 0 (None) to 4 (Severe). Complete loss of response is defined as both CR-PCSS and PR-PCSS ratings returned to the baseline severity of the double-blind study or worse for both the buttocks. Time to complete loss of response (days) was defined as the number of days from Screening assessment of composite improvement in cellulite severity in CR-PCSS and PR-PCSS to the time at which complete loss of response was observed for the first time. |
Countries
United States
Participant flow
Pre-assignment details
Rollover participants from the parent studies, EN3835-302 or EN3835-303 (CCH-aaes-treated or placebo-treated) were unblinded at Day 180 (after observation phase) and only participants who received active CCH-aaes remained in this Open-label Phase of the study.
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants Participants who received CCH-aaes or placebo treatment in the parent studies were followed for 180 days of observation with no treatment. Participants who were identified as received CCH-aaes in the parent studies following the 180-day Observation Phase entered the Open-label Phase. Participants in the Open-label Phase who qualified for, and opted for, retreatment were administered CCH-aaes up to 1.68 mg at 3 treatment sessions, at 21-day intervals and participants who received placebo during the parent studies were discontinued. | 483 |
| Total | 483 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 180 Days Observational Phase | Lost to Follow-up | 1 | 0 |
| 180 Days Observational Phase | Participants who Received Placebo in Parent Studies were Discontinued | 0 | 238 |
| 180 Days Observational Phase | Withdrawal by Subject | 40 | 2 |
| Open-label Phase | Adverse Event | 4 | 0 |
| Open-label Phase | Lost to Follow-up | 35 | 0 |
| Open-label Phase | Other than Specified | 5 | 0 |
| Open-label Phase | Withdrawal by Subject | 54 | 0 |
Baseline characteristics
| Characteristic | Overall Participants |
|---|---|
| Age, Continuous | 47.6 years STANDARD_DEVIATION 10.73 |
| Body Mass Index (BMI) | 31.00 kg/m^2 STANDARD_DEVIATION 7.108 |
| Race/Ethnicity, Customized Ethnicity: Hispanic or Latino | 90 Participants |
| Race/Ethnicity, Customized Ethnicity: Not Hispanic or Latino | 393 Participants |
| Race/Ethnicity, Customized Race : American Indian or Alaska Native | 2 Participants |
| Race/Ethnicity, Customized Race : Asian | 3 Participants |
| Race/Ethnicity, Customized Race : Black or African American | 87 Participants |
| Race/Ethnicity, Customized Race : Multiple | 6 Participants |
| Race/Ethnicity, Customized Race : Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Race : Other | 2 Participants |
| Race/Ethnicity, Customized Race : White | 382 Participants |
| Sex: Female, Male Female | 483 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 243 | 0 / 240 | 0 / 202 | 0 / 55 |
| other Total, other adverse events | 27 / 243 | 0 / 240 | 7 / 202 | 31 / 55 |
| serious Total, serious adverse events | 1 / 243 | 1 / 240 | 3 / 202 | 3 / 55 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any unfavorable or unintended change in body structure (signs), body function (symptoms), laboratory result, or worsening of a pre-existing condition associated temporally with the use of the study medication whether or not considered related to the study medication. TEAEs were defined as any AEs with a start date equal to or after the date of the first injection. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Up to Day 1080
Population: Day 180 Observation Phase Population included all rollover participants who completed the parent studies (EN3835-302 or EN3835-303) (CCH-aaes-treated or placebo-treated). Open-label Phase Population included participants who received CCH-aaes in the parent study and who consented to continue in the Open-label Phase of the study. Open-label CCH-aaes Retreatment Population included participants in the Open-label Phase who qualified for, and opted for, retreatment with CCH-aaes.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Day 180 Observation Phase: CCH-aaes Treatment in Parent Studies EN3835-302/303 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 58 Participants |
| Day 180 Observation Phase: Placebo Treatment in Parent Studies EN3835-302/303 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 29 Participants |
| Open-label Phase (Prior to Retreatment) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 43 Participants |
| Open-label CCH-aaes Retreatment Phase | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 45 Participants |
Primary
Percentage of Participants Who Were Seropositive for Anti-Drug Antibodies (ADAs) After CCH-aaes Treatment
Serum samples were analyzed for ADAs. The percentage of participants who developed ADAs (seropositive results) during the Open-label Phase of the study are reported.
Time frame: From Day 180 (Open-label Phase) up to Day 1080
Population: Open-label Phase Population included participants who received CCH-aaes in the parent study and who consented to continue in the Open-label Phase of the study. Open-label CCH-aaes Retreatment Population included participants in the Open-label Phase who qualified for, and opted for, retreatment with CCH-aaes. Participants who received placebo during the parent studies did not continue in the Open-label Phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Day 180 Observation Phase: CCH-aaes Treatment in Parent Studies EN3835-302/303 | Percentage of Participants Who Were Seropositive for Anti-Drug Antibodies (ADAs) After CCH-aaes Treatment | 98.2 percentage of participants |
| Day 180 Observation Phase: Placebo Treatment in Parent Studies EN3835-302/303 | Percentage of Participants Who Were Seropositive for Anti-Drug Antibodies (ADAs) After CCH-aaes Treatment | 100 percentage of participants |
Secondary
Time to 1-Level Reduction of Response in CR-PCSS and PR-PCSS
CR-PCSS and PR-PCSS assess improvement in cellulite severity using a 5-level scale ranging from 0 (None) to 4 (Severe). Time to reduction of response (days) was defined as the number of days from Screening assessment of composite improvement in cellulite severity in CR-PCSS and PR-PCSS to the time at which 1-level composite worsening of response was observed for the first time.
Time frame: From Day 180 (Open-label Observation Phase) up to Day 1080
Population: This assessment includes both 1-level and 2-level composite responders in the parent studies who had a 1-level reduction of response in CR-PCSS and PR-PCSS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 180 Observation Phase: CCH-aaes Treatment in Parent Studies EN3835-302/303 | Time to 1-Level Reduction of Response in CR-PCSS and PR-PCSS | 356.5 days | Standard Deviation 232.43 |
Secondary
Time to 2-Level Reduction of Response in Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS)
CR-PCSS and PR-PCSS assess improvement in cellulite severity using a 5-level scale ranging from 0 (None) to 4 (Severe). Time to reduction of response (days) was defined as the number of days from Screening assessment of composite improvement in cellulite severity in PR-PCSS and CR-PCSS to the time at which a 2-level composite worsening of response was observed for the first time.
Time frame: From Day 180 (Open-label Observation Phase) up to Day 1080
Population: Participants who were treated with CCH-aaes and had a 2-level composite response in CR-PCSS and PR-PCSS in the parent studies and who consented to continue in the Open-label Phase of this study. Participants who had a 2-level reduction in response in CR-PCSS and PR-PCSS were to be assessed for time to event.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Day 180 Observation Phase: CCH-aaes Treatment in Parent Studies EN3835-302/303 | Time to 2-Level Reduction of Response in Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS) | NA days |
Secondary
Time to Complete Loss of Response in CR-PCSS and PR-PCSS
CR-PCSS and PR-PCSS assess improvement in cellulite severity using a 5-level scale ranging from 0 (None) to 4 (Severe). Complete loss of response is defined as both CR-PCSS and PR-PCSS ratings returned to the baseline severity of the double-blind study or worse for both the buttocks. Time to complete loss of response (days) was defined as the number of days from Screening assessment of composite improvement in cellulite severity in CR-PCSS and PR-PCSS to the time at which complete loss of response was observed for the first time.
Time frame: From Day 180 (Open-label Observation Phase) up to Day 1080
Population: This assessment includes both 1-level and 2-level composite responders in the parent studies who had complete loss of response in CR-PCSS and PR-PCSS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 180 Observation Phase: CCH-aaes Treatment in Parent Studies EN3835-302/303 | Time to Complete Loss of Response in CR-PCSS and PR-PCSS | 238.2 days | Standard Deviation 85.75 |