EN3835 for the Treatment of Edematous Fibrosclerotic Panniculopathy (Commonly Known as Cellulite)

Study Overview
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Brief Summary
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The study will evaluate the safety, effectiveness, and immunogenicity of EN3835 in the treatment of adult women with Edematous Fibrosclerotic Panniculopathy (Commonly known as Cellulite).

Official Title
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EN3835 for the Treatment of Edematous Fibrosclerotic Panniculopathy (Commonly Known as Cellulite)

Conditions
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Cellulite, Edematous Fibrosclerotic Panniculopathy

Intervention / Treatment
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* Biological: COLLAGENASE CLOSTRIDIUM HISTOLYTICUM
* Biological: Placebo Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be a female ≥18 years of age At Screening visit, have at least 1 quadrant with: a score of 3 or 4 (moderate or severe) as reported by the subject (PR- PCSS), and a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS), and a Hexsel CSS score no greater than 13 At Day 1 visit, have an assigned quadrant with: a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS), and a Hexsel CSS score no greater than 13 Be willing to apply sunscreen to the selected treatment quadrant before each exposure to the sun while participating in the study (ie, screening through end of study). Be judged to be in good health, based upon the results of a medical history, physical examination, and laboratory profile at screening Have a negative urine pregnancy test at screening and be using an effective contraception method (eg, abstinence, intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, or double barrier method) for at least 1 menstrual cycle prior to study enrollment and for the duration of the study; or be menopausal defined as 12 months of amenorrhea in the absence of other biological or physiological causes, as determined by the investigator; or post-menopausal for at least 1 year; or be surgically sterile. Be willing and able to cooperate with the requirements of the study Voluntarily sign and date an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee/Human Research Ethics Committee (IRB/IEC/HREC). Be able to read, complete and understand the Patient Reported Outcomes rating instruments in English Exclusion Criteria: Has any of the following conditions: Thyroid disease, unless controlled with medication for ≥6 months Uncontrolled diabetes mellitus, as determined by the Investigator Uncontrolled hypertension, as determined by the Investigator Vascular disorder (eg, phlebitis or varicose veins) in area to be treated Cushing's disease and/or use of systemic corticosteroids at a total daily dose greater than 5 mg prednisone (or equivalent) History of lower extremity thrombosis or post-thrombosis syndrome Documented autoimmune disorder such as lupus erythematosus, rheumatoid arthritis Inflammation or active infection in area to be treated Active cutaneous alteration in area to be treated including rash, eczema, psoriasis or skin cancer History of keloidal scarring or abnormal wound healing Coagulation disorder Taking a medication for chronic anticoagulation (except for ≤150 mg aspirin daily)

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EN3835 Active<br>EN3835 0.84 mg (Collagenase Clostridium Histolyticum). Each subject can receive up to three treatment sessions. Each treatment session will be separated by approximately 21 days. | Biological: COLLAGENASE CLOSTRIDIUM HISTOLYTICUM<br>* Injectable intervention<br>* Other names: Xiaflex;|
| Placebo Comparator: EN3835 Placebo<br>Placebo | Biological: Placebo Comparator<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Composite Responders of at Least 2-Level Improvement of Severity | Percentage of composite responders defined as subjects with an improvement from baseline of at least 2-levels of severity on each, the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), at Day 71 in the ITT population. The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement on each scale for example would represent a change from a 4 (severe) to a 2 (mild). In order to be considered a responder a subject needs to have at least a 2-level improvement on both scales. | Baseline, Day 71 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Composite Responders of at Least 1-Level Improvement of Severity | Percentage of composite responders defined as subjects with improvement from baseline of at least 1-level of severity on each, the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), at Day 71 in the ITT population. The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 1-level improvement on each scale for example would represent a change from a 4 (severe) to a 3 (moderate). In order to be considered a responder a subject needs to have at least a 1-level improvement on both scales. | Baseline, Day 71 | 
| CR-PCSS Responder Analysis: 2-Levels of Severity | Percentage of subjects with improvement from baseline of at least 2-levels of severity on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) at Day 71.The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement would be for example a change from 4 (severe) to 2 (mild). | Baseline, Day 71 | 
| CR-PCSS Responder Analysis: 1-Level of Severity | Percentage of subjects with improvement from baseline of at least 1-level of severity on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) at Day 71.The CR-PCSS is a photonumeric scale that was used by the investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 1-level improvement would be for example a change from 4 (severe) to 3 (moderate). | Baseline, Day 71 | 
| CR-PCSS Change From Baseline | The CR-PCSS is a photonumeric scale that was used by the investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). Change is Day 71 study visit rating minus baseline visit; negative values indicate a lessening in cellulite severity. | Baseline, Day 71 | 
| PR-PCSS Responder Analysis: 2-Levels of Severity | Percentage of subjects with improvement from baseline of at least 2-levels of severity on the subject-rated Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) at Day 71.The PR-PCSS is a photonumeric scale that was used by the subject to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement would be for example a change from 4 (severe) to 2 (mild). | Baseline, Day 71 | 
| PR-PCSS Responder Analysis: 1-Level of Severity | Percentage of subjects with improvement from baseline of at least 1-level of severity on the subject-rated Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) at Day 71.The PR-PCSS is a photonumeric scale that was used by the subject to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 1-level improvement would be for example a change from 4 (severe) to 3 (moderate). | Baseline, Day 71 | 
| PR-PCSS Change From Baseline | The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). Change is Day 71 study visit rating minus baseline visit; negative values indicate a lessening in cellulite severity. | Baseline, Day 71 | 
| Investigator Assessment of Improvement Based on the Investigator Global Aesthetic Improvement Scale (I-GAIS) | On Day 71, the Investigator determined the degree of improvement from baseline in the treated area using the 7-point I-GAIS. Ratings could be improved (+1), much improved (+2), or very much improved (+3), or no change (0), or worse (-1), much worse (-2) or very much worse (-3). | Day 71 | 
| Subject Assessment of Improvement Based on the Subject Global Aesthetic Improvement Scale (S-GAIS) | At Day 71, subjects were asked to rate their opinion of the overall improvement of their treated area using the 7-point S-GAIS. Ratings could be improved (+1), much improved (+2), or very much improved (+3), or no change (0), or worse (-1), much worse (-2) or very much worse (-3) | Day 71 | 
| Subject Satisfaction Assessment Based on the the Subject Satisfaction Scale | At Day 71, subjects were asked to rate their satisfaction with cellulite treatment using the 5-point subject satisfaction scale. Ratings could be satisfied (+1), very satisfied (+2), neither satisfied nor dissatisfied (0), or dissatisfied (-1), very dissatisfied (-2). | Day 71 | 
| Change in the Hexsel Cellulite Severity Scale (CSS) Total Score | Investigator used the Hexsel CSS to assess the severity of cellulite. The total score could range from 0 (no cellulite) to 15 (extremely severe cellulite). Negative change in Hexsel CSS total score indicates an improvement in cellulite severity | Baseline, Day 71 |