CCH Treatment of Cellulite in the Presence of Dermal Laxity With Comparison Between Two (2) Different Injection Techniques

Study Overview
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Brief Summary
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This study is designed to investigate the safety and efficacy of collagenase clostridium histolyticum (CCH) for the treatment of mild to moderate edematous fibrosclerotic panniculopathy (cellulite) in participants with moderate to severe dermal laxity in the buttocks or thighs with comparison between two (2) different CCH injection techniques.

Official Title
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A Phase 2 Multicenter, Open-label, Randomized, Parallel-group, Multiple-dose Study to Assess the Effectiveness, Safety and Satisfaction With Collagenase Clostridium Histolyticum Grid Technique Injections of Buttock or Thigh Cellulite With Laxity in Adult Females

Conditions
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Edematous Fibrosclerotic Panniculopathy, Cellulite, Laxity; Skin

Intervention / Treatment
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* Drug: collagenase clostridium histolyticum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a body mass index of 18 to <29.9 kilograms/square meters Have either both buttocks or both posterolateral thighs with: Score of 2 or 3 (mild or moderate cellulite) as reported by the investigator using the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) Hexsel Cellulite Severity Scale (CSS) Subsection D Grade of Laxity, Flaccidity, or Sagging Skin score of 2 or 3 (moderate or severe) as determined by the investigator Have a negative pregnancy test or be of non-childbearing potential Be willing and able to cooperate with the requirements of the study Be willing to apply sunscreen to the treatment areas before each exposure to the sun for the duration of the study (from the Screening Visit through the Day 180/Early Termination Visit). Exclusion Criteria: Has a history of hypersensitivity or allergy to collagenase or any other excipients of CCH. During Screening has a CR-PCSS score of less than 2 or greater than 3 for the area to be treated (buttocks or thighs) and/or has a Hexsel CSS Subsection D Grade of Laxity, Flaccidity, or Sagging Skin score of less than 2 or greater than 3 (severe) for the areas to be treated (buttocks or thighs). Has a coagulation disorder, which requires anticoagulant or antiplatelet medication during the study (except for ≤150 mg aspirin daily), or has taken anticoagulant or antiplatelet medication(s) within 14 days before injection of study treatment (except for ≤150 mg aspirin daily). Is a prisoner, an individual with impaired decision making capacity, 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), or in the judgment of the investigator the participant is disadvantaged and vulnerable to coercion due to lack of education, or due to poor economic circumstances. Has received any collagenase treatments at any time prior to treatment in this study and/or has received EN3835 or CCH in a previous investigational study for cellulite. Is pregnant and/or is breast-feeding or plans to become pregnant and/or to breast-feed during the course of the study. Has a history of scarring due to keloids or abnormal wound healing. Has local (in areas to be treated) conditions (thrombosis, vascular disorder, active infection/inflammation, active cutaneous alteration, tattoo/mole) that restricts study participation Has history of drug or alcohol abuse within the 5 years prior to the Screening Visit. Has evidence of clinically significant abnormalities, as judged by the investigator, in any of the following: physical examination findings, electrocardiogram (ECG), clinical laboratory values, or vital signs. The sponsor's medical monitor will be required to review the results for confirmation of eligibility in the case of any of the following: abnormalities in electrocardiograms indicating corrected QT interval (QTc) prolongation of 470 milliseconds or greater; and clinical laboratory values of liver enzymes Has used or intends to use any of the local application/therapies/injections/procedures that restricts study participation. Has any other condition(s) that, in the investigator's opinion, might indicate the participant to be unsuitable for the study. For the subset of participants participating in the collection of ultrasound data, the following exclusions will apply: participants will be excluded who have: a history of a spinal laminectomy, a previous history or presence of vascular abnormalities (for example, deep vein thrombosis, thrombophlebitis), a healing fracture, an impaired sensation within, or near, the planned treatment area, or any implants within, or near, the planned treatment area.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Uniform 0.1-milliliters (mL) 1-Aliquot Grid Injection Technique (Buttock)<br>Dose per participant per treatment visit = up to 1.68 milligrams (mg) of CCH (0.84 mg in each treatment area) | Drug: collagenase clostridium histolyticum<br>* Delivered via uniform grid injection techniques.<br>* Other names: CCH;|
| Active Comparator: Uniform 0.3-mL 2-Aliquot Grid Injection Technique (Buttock)<br>Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area) | Drug: collagenase clostridium histolyticum<br>* Delivered via uniform grid injection techniques.<br>* Other names: CCH;|
| Active Comparator: Uniform 0.1-mL 1-Aliquot Grid Injection Technique (Thigh)<br>Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area) | Drug: collagenase clostridium histolyticum<br>* Delivered via uniform grid injection techniques.<br>* Other names: CCH;|
| Active Comparator: Uniform 0.3-mL 2-Aliquot Grid Injection Technique (Thigh)<br>Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area) | Drug: collagenase clostridium histolyticum<br>* Delivered via uniform grid injection techniques.<br>* Other names: CCH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of 1-Level Responders (+1 or Better Score) on the Investigator-Global Aesthetic Improvement Scale (I-GAIS) for Either Buttock or Either Thigh | I-GAIS is a 7-point scale rating global aesthetic improvement in appearance, compared to pretreatment, as judged by the investigator ranging from Very Much Worse (-3), Much Worse (-2), Worse (-1), No Change (0), Improved (+1), Much Improved (+2), and Very Much Improved (+3). One-level I-GAIS Responder for a treatment area (left buttock, right buttock, left thigh, or right thigh) was defined as any participant with an improved (+1, +2 or +3) score on the I-GAIS at the analysis visit for that treatment area. The percentage of participants who were 1-level responders for either buttock (right or left) or either thigh (right or left) is presented. | Day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of 1-Level Responders (+1 or Better Score) on the I-GAIS for Either Buttock or Either Thigh | I-GAIS is a 7-point scale rating global aesthetic improvement in appearance, compared to pretreatment, as judged by the investigator ranging from Very Much Worse (-3), Much Worse (-2), Worse (-1), No Change (0), Improved (+1), Much Improved (+2), and Very Much Improved (+3). One-level I-GAIS Responder for a treatment area (left buttock, right buttock, left thigh, or right thigh) was defined as any participant with an improved (+1, +2 or +3) score on the I-GAIS at the analysis visit for that treatment area. The percentage of participants who were 1-level responders for either buttock (right or left) or either thigh (right or left) is presented. | Days 28, 56, 84, 112, and 140 | 
| Percentage of 1-Level Responders (+1 or Better Score) on the Subject Global Aesthetic Improvement Scale (S-GAIS) for Either Buttock or Either Thigh | S-GAIS assessments were based on digital photographs, and were performed separately for each of 2 treatment areas. S-GAIS is a 7-point scale rating global aesthetic improvement in appearance, compared to pretreatment, as judged by the participant ranging from Very Much Worse (-3), Much Worse (-2), Worse (-1), No Change (0), Improved (+1), Much Improved (+2), and Very Much Improved (+3). One-level S-GAIS Responder for a treatment area (left buttock, right buttock, left thigh, or right thigh) was defined as any participant with an improved (+1, +2 or +3) score on the S-GAIS at the analysis visit for that treatment area. The percentage of participants who were 1-level responders for either buttock (right or left) or either thigh (right or left) is presented. | Days 28, 56, 84, 112, 140, and 180 | 
| Change From Baseline in Body-Q Appraisal of Cellulite Total Score | The Body-Q Appraisal of Cellulite is a subset of 11 questions from the Body-Q questionnaire developed to measure participant perceptions of weight loss and/or body contouring. Total score is the sum of all 11 question scores. The minimum possible total score is 11 and the maximum possible total score is 44. Higher scores indicate the individual is less bothered by their cellulite. | Baseline, Day 180 | 
| Change From Baseline in Hexsel Cellulite Severity Scale (CSS) Subsection D Severity Score | Hexsel CSS is a photonumeric scale that looks at 5 key morphologic features of cellulite using a 4-point scale from a low of 0 to high of 3: 0 (absence of laxity, flaccidity, or sagging skin), 1 (slight draped appearance), 2 (moderate draped appearance), and 3 (severe draped appearance). The investigator or qualified designee used the Hexsel CSS Subsection D to assess the severity of dermal laxity in each buttock or each thigh independently. A decrease from baseline indicated a better outcome. | Baseline, Days 28, 56, 84, 112,140, and 180 | 
| Percentage of Participants Positive for Anti-AUX-I and Anti-AUX-II Antibodies | Blood samples were collected to assess anti-clostridial class I collagenase (AUX-I) and anti-Clostridial class II collagenase (AUX-II) antibody levels. The percentage of participants who were positive for anti-AUX-I and anti-AUX-II antibodies are presented. | Day 180 | 
| Percentage of Participants Positive for Neutralizing Antibodies to AUX-I and AUX-II | Blood samples were collected to assess neutralizing antibodies to AUX-I and AUX-II. The percentage of participants who were positive for neutralizing antibodies to AUX-I and AUX-II are presented. | Day 180 |