Real World CCH Study in Adult Females With Cellulite

Study Overview
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Brief Summary
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This is a multicenter, open-label, multiple dose, 2 cohort, Phase 3b study to assess the safety and efficacy of CCH in adult women with mild or moderate edematous fibrosclerotic panniculopathy (EFP). Cohort 1 will include approximately 80 subjects with mild or moderate EFP in the posterolateral thighs and Cohort 2 will include approximately 70 subjects with mild or moderate EFP in the buttocks.

Official Title
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A Real World, Multicenter, Open-Label, Multiple Dose Study to Assess the Effectiveness of, and Satisfaction With, CCH Treatment of Buttocks or Thigh Cellulite in Adult Females

Conditions
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Edematous Fibrosclerotic Panniculopathy (EFP), Cellulite

Intervention / Treatment
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* Drug: EN3835


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have both buttocks or both posterolateral thighs with: A score of 2 or 3 (mild or moderate) as reported by the investigator using the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS). A Hexsel Cellulite Severity Scale (CSS) Subsection D Grade of Laxity, Flaccidity, or Sagging Skin score of 0 (absence of laxity, flaccidity, or sagging skin), or 1 (slightly draped appearance) at the Screening Visit only. Be willing to apply sunscreen to the treatment areas before each exposure to the sun for the duration of the study. Be judged to be in good health. Have a negative pregnancy test. Be willing and able to cooperate with the requirements of the study. Exclusion Criteria: Is from a vulnerable population, as defined by the United States (US) Code of Federal Regulations (CFR) Title 45, Part 46, Section 46.111(b) and other local and national regulations, including but not limited to, employees (temporary, part-time, full-time, etc.) or a family member of the research staff conducting the study, or of the sponsor, or of the contract research organization, or of the Institutional Review Board (IRB)/Independent Ethics Committee (IEC). Has a history of sensitivity or allergy to collagenase or any other excipient of CCH. Has systemic conditions (coagulation disorders, malignancy, keloidal scarring, abnormal wound healing) that restricts study participation. Has local (in areas to be treated) conditions (thrombosis, vascular disorder, active infection/inflammation, active cutaneous alteration, tattoo/mole) that restricts study participation. Has skin laxity or linear undulations on the treatment region (both buttocks or both thighs) that can be effaced by lifting skin. Has a Hexsel CSS Subsection D Grade of laxity, flaccidity, or sagging skin of 2 (moderate draped appearance) or 3 (severe draped appearance). Requires anticoagulant or antiplatelet medication during the study. Has used or intends to use any of the local applications/therapies/injections/procedures that restricts study participation. Has received any collagenase treatments at any time prior to treatment in this study and/or has received previous treatment with EN3835 or CCH for cellulite. Has received treatment with an investigational product within 30 days (or 5 half-lives, whichever is longer) of the Screening Visit. Is pregnant and/or is providing breast milk in any manner, or plans to become pregnant and/or to provide breast milk during the course of the study. Has any other condition(s) that, in the investigator's opinion, might indicate the subject to be unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Posterolateral Thigh<br>EN3835 up to 1.68mg (Collagenase Clostridium Histolyticum) | Drug: EN3835<br>* Collagenase Clostridium Histolyticum (CCH)<br>|
| Experimental: Cohort 2: Buttocks<br>EN3835 up to 1.68mg (Collagenase Clostridium Histolyticum) | Drug: EN3835<br>* Collagenase Clostridium Histolyticum (CCH)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Participants With Improved (+1 or Better) Score on I-GAIS for Either Posterolateral Thigh | Investigator Global Aesthetic Improvement Scale (I-GAIS) is a 7-point scale rating global aesthetic improvement in appearance, compared to pretreatment, as judged by the investigator. The rating categories are Very Much Worse, Much Worse, Worse, No Change, Improved, Much Improved, and Very Much Improved. | 90 Days | 
| The Proportion of Participants With Improved (+1 or Better) Score on I-GAIS for Either Buttock | Investigator Global Aesthetic Improvement Scale (I-GAIS) is a 7-point scale rating global aesthetic improvement in appearance, compared to pretreatment, as judged by the investigator. The rating categories are Very Much Worse, Much Worse, Worse, No Change, Improved, Much Improved, and Very Much Improved. | 90 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in CR-PCSS for Each Buttock | Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) is a 5-point photonumeric scale rating cellulite severity from 0 (none) to 4 (severe) from a clinician's perspective. | Day 22, 43, 90 and 180 | 
| Mean Change From Baseline in Body Q Appraisal of Cellulite for Posterolateral Thigh Based on Total Score | The Body-Q Appraisal of Cellulite is a subset of questions from the Body-Q questionnaire developed to measure participant perceptions of weight loss and/or body contouring. The minimum possible score is 11 and the maximum possible score is 44. Higher scores indicate the individual is less bothered by their cellulite. Copyright Memorial Sloan-Kettering Cancer Center | Day 90, Day 180 | 
| Mean Change From Baseline in Body Q Appraisal of Cellulite for Buttock Based on Total Score | The Body-Q Appraisal of Cellulite is a subset of questions from the Body-Q questionnaire developed to measure participant perceptions of weight loss and/or body contouring. The minimum possible score is 11 and the maximum possible score is 44. Higher scores indicate the individual is less bothered by their cellulite. Copyright Memorial Sloan-Kettering Cancer Center | Day 90, Day 180 | 
| The Proportion of Participants With Improved (+1 or Better) Score on I GAIS for Either Posterolateral Thigh | Investigator Global Aesthetic Improvement Scale (I-GAIS) is a 7-point scale rating global aesthetic improvement in appearance, compared to pretreatment, as judged by the investigator. The rating categories are Very Much Worse, Much Worse, Worse, No Change, Improved, Much Improved, and Very Much Improved. | Day 22, 43, and 180 | 
| The Proportion of Participants With Improved (+1 or Better) Score on I-GAIS for Either Buttock | Investigator Global Aesthetic Improvement Scale (I-GAIS) is a 7-point scale rating global aesthetic improvement in appearance, compared to pretreatment, as judged by the investigator. The rating categories are Very Much Worse, Much Worse, Worse, No Change, Improved, Much Improved, and Very Much Improved. | Day 22, 43, and 180 | 
| Percentage of Participants With Positive Antibody Titers for Anti-AUX-I and Anti AUX-II (Posterolateral Thigh) | Immunogenicity samples with a positive titer value will undergo a log transformation for analyses. Samples with titer level less than 10 were assigned or imputed as a log transformed titer of 1 for analyses | Day 1, 90, and 180 | 
| Percentage of Participants With Positive Antibody Titers for Anti-AUX-I and Anti AUX-II (Buttocks) | Immunogenicity samples with a positive titer value will undergo a log transformation for analyses. Samples with titer level less than 10 were assigned or imputed as a log transformed titer of 1 for analyses | Day 1, 90 and 180 | 
| Presence of Neutralizing Antibody (NAb) Anti AUX-I and AUX-II (Posterolateral Thigh) | All the samples with positive ADAs for the participants who had had every other titer levels in the first quartile and fourth quartile of all positive ADAs at Day 90 (performed separately for AUX-I and AUX-II) were tested for NAb. | Day 1, 90 and 180 | 
| Presence of NAb Anti AUX-I and AUX-II (Buttocks) | All the samples with positive ADAs for the participants who had had every other titer levels in the first quartile and fourth quartile of all positive ADAs at Day 90 (performed separately for AUX-I and AUX-II) were tested for NAb. | Day 1, 90 and 180 |