Long-Term Study of EN3835 (CCH-aaes) in Edematous Fibrosclerotic Panniculopathy (Cellulite)

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 3b, Open-Label, Long-Term Study to Evaluate the Safety and Temporal Pattern of Response of EN3835 in the Treatment of Edematous Fibrosclerotic Panniculopathy

Conditions
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Edematous Fibrosclerotic Panniculopathy, Cellulite

Intervention / Treatment
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* Biological: CCH-aaes
* Other: Observation


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria All Participants (Through Day 180): Voluntarily sign and date an informed consent agreement Have participated in and completed the double-blind Phase 3 study EN3835-302 or EN3835-303 Be willing to apply sunscreen to the buttocks before each exposure to the sun and/or tanning booths while participating in the study Be judged to be in good health Be willing and able to cooperate with the requirements of the study 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): Intends to or has used any of the local applications/therapies/injections/procedures that restricts study participation Intends to use tanning spray or tanning booths during this period Has received or intends to receive an investigational drug or treatment, other than the treatment received in study EN3835-302/303 during this period Any other condition(s) that, in the Investigator's opinion, might indicate the participant to be unsuitable for the study Additional Exclusion Criteria may apply Post Day 180: 1. Has received any collagenase treatments at any time since completion of the double-blind study (EN3835-302 or EN3835-303). Key Exclusion Criteria for Participants Eligible for Retreatment: 1. Has systemic conditions (coagulation disorders, malignancy, keloidal scar, abnormal wound healing) that restricts study participation Has local (in areas to be treated) conditions (thrombosis, vascular disorder, active infection/inflammation, skin laxity, flaccidity and/or skin sagging, active cutaneous alteration, tattoo/mole) that restricts study participation Requires anticoagulant or antiplatelet medication during the study Prior to and during the course of retreatment, is nursing or providing breast milk in any manner, intends to become pregnant during the study, or intends to use tanning spray or tanning booths during the study Has received an investigational drug or treatment, other than treatment in study EN3835-302/303, within 30 days before retreatment with study drug Has a known systemic allergy to collagenase or any other excipient of study drug Has received any collagenase treatments at any time since completion of the double-blind study Any other condition(s) that, in the Investigator's opinion, might indicate the participant to be unsuitable for retreatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CCH-aaes Treatment in Parent Studies (EN3835-302/303)<br>Participants who received CCH-aaes treatment in EN3835-302/303 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 and entered the Open-label Phase of the study. 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. | Biological: CCH-aaes<br>* Administered to participants who qualified for, and opted for, retreatment.<br>* Other names: QWO™;Other: Observation<br>* No treatment administered during 180 days of observation.<br>|
| Other: Placebo Treatment in Parent Studies (EN3835-302/303)<br>Participants who received placebo in the parent studies, were followed for 180 days of observation with no treatment. After Day 180, all participants who received placebo during the double-blind parent studies were discontinued. No treatment was administered. | Other: Observation<br>* No treatment administered during 180 days of observation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to Day 1080 | 
| 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. | From Day 180 (Open-label Phase) up to Day 1080 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From Day 180 (Open-label Observation Phase) up to Day 1080 | 
| 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. | From Day 180 (Open-label Observation Phase) up to Day 1080 | 
| 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. | From Day 180 (Open-label Observation Phase) up to Day 1080 |