Histopathology Following CCH Injection

Study Overview
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Brief Summary
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To evaluate the histopathology of subcutaneous tissue isolated after single or multiple Collagenase Clostridium Histolyticum (CCH) injection techniques in adult female participants undergoing abdominoplasty.

Official Title
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A Phase 2B, Open-Label Study to Explore Tissue Histopathology Following Subcutaneous Injection of Collagenase Clostridium Histolyticum Using An Abdominoplasty Model

Conditions
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Characteristics of Subcutaneous Tissue

Intervention / Treatment
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* Drug: Collagenase Clostridium Histolyticum Single Injection Technique
* Drug: Collagenase Clostridium Histolyticum Multiple Injection Technique


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be adequately informed and understand the nature and risks of the study and be able to provide consent. Be undergoing planned elective abdominoplasty. Be willing to have their tissue donated for evaluation. 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 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 systemic conditions (coagulation disorders, malignancy, keloidal scar, abnormal wound healing) that restricts study participation. Has local (in the areas to be treated) conditions (thrombosis, vascular disorder, active infection/inflammation, active cutaneous alteration, tattoo/mole) that restricts study participation. Required use of anticoagulant or antiplatelet medication (except ≤ 150 mg aspirin daily) before or during participation in the trial. Past history of any abdominal surgery, including but not limited to: liposuction, caesarean section, appendectomy, cholecystectomy, or umbilical hernia repair. Has used or intends to use any local applications/therapies/injections/procedures that restricts study participation. Is presently nursing or providing breast milk in any manner. Intends to become pregnant during the study. Intends to initiate an intensive sport or exercise program regimen during the study. Intends to use any tanning spray or tanning booths during the study. Has received any investigational drug or treatment within 30 days prior to first injection of study drug. Has a known systemic allergy to collagenase or any other excipient of study drug. Has received any collagenase treatment at any time prior to treatment in this study. 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: 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: CCH Single Injection Technique<br>Participants were administered 0.07 milligrams (mg) CCH subcutaneously using a single injection technique. Each participant had 2 marked areas (Area 1 and Area 2) of the abdomen selected for injection. Area 1 was administered CCH on Days -43 and -22. Area 2 was administered CCH on Day -14. | Drug: Collagenase Clostridium Histolyticum Single Injection Technique<br>* CCH was injected subcutaneously using a single injection technique. Dose per each administration was 0.07 mg.<br>* Other names: CCH;|
| Experimental: Group 2: CCH Single Injection Technique<br>Participants were administered 0.07 mg CCH subcutaneously using a single injection technique. Each participant had 2 marked areas (Area 1 and Area 2) of the abdomen selected for injection. Area 1 was administered CCH on Days -24 and -3. Area 2 was administered CCH on Day -3. | Drug: Collagenase Clostridium Histolyticum Single Injection Technique<br>* CCH was injected subcutaneously using a single injection technique. Dose per each administration was 0.07 mg.<br>* Other names: CCH;|
| Experimental: Group 3: CCH Single Injection Technique<br>Participants were administered 0.07 mg CCH subcutaneously using a single injection technique. Each participant had 2 marked areas (Area 1 and Area 2) of the abdomen selected for injection. Area 1 was administered CCH on Days -22 and -1. Area 2 was administered CCH on Day -1. | Drug: Collagenase Clostridium Histolyticum Single Injection Technique<br>* CCH was injected subcutaneously using a single injection technique. Dose per each administration was 0.07 mg.<br>* Other names: CCH;|
| Experimental: Group 4: CCH Multiple Injection Technique<br>Participants were administered 0.0653 mg CCH subcutaneously using a multiple injection technique. Each participant had 2 marked areas (Area 1 and Area 2) of the abdomen selected for injection. Area 1 was administered CCH on Days -43 and -22. Area 2 was administered CCH on Day -14. | Drug: Collagenase Clostridium Histolyticum Multiple Injection Technique<br>* CCH was injected subcutaneously using a multiple injection technique. Dose per each administration was 0.0653 mg.<br>* Other names: CCH;|
| Experimental: Group 5: CCH Multiple Injection Technique<br>Participants were administered 0.0653 mg CCH subcutaneously using a multiple injection technique. Each participant had 2 marked areas (Area 1 and Area 2) of the abdomen selected for injection. Area 1 was administered CCH on Days -24 and -3. Area 2 was administered CCH on Day -3. | Drug: Collagenase Clostridium Histolyticum Multiple Injection Technique<br>* CCH was injected subcutaneously using a multiple injection technique. Dose per each administration was 0.0653 mg.<br>* Other names: CCH;|
| Experimental: Group 6: CCH Multiple Injection Technique<br>Participants were administered 0.0653 mg CCH subcutaneously using a multiple injection technique. Each participant had 2 marked areas (Area 1 and Area 2) of the abdomen selected for injection. Area 1 was administered CCH on Days -22 and -1. Area 2 was administered CCH on Day -1. | Drug: Collagenase Clostridium Histolyticum Multiple Injection Technique<br>* CCH was injected subcutaneously using a multiple injection technique. Dose per each administration was 0.0653 mg.<br>* Other names: CCH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Histologic Change in a Tissue Specimen That Was Injected With CCH | Tissue specimens isolated from participants undergoing an abdominoplasty procedure were observed for histopathological structure changes of tissues post treatment with CCH. The number of participants with a histologic change (as determined by the pathologist) in tissue dosed with CCH relative to control tissue (tissue not dosed with CCH) is reported. | Up to collection of the excised abdominal tissue on Day 0 (day of abdominoplasty) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Histologic Change in a Tissue Specimen After 2 CCH Dose Injections Relative to a Tissue Specimen After 1 CCH Dose Injection | Tissue specimens isolated from participants undergoing an abdominoplasty procedure were observed for histopathological structure changes of tissues post treatment with CCH. The number of participants with a histologic change (as determined by the pathologist) in a tissue specimen injected with 2 CCH dose injections (Treatment Area 1) relative to 1 CCH dose injection (Treatment Area 2) is reported. | Up to collection of the excised abdominal tissue on Day 0 (day of abdominoplasty) | 
| Number of Participants With Anti-AUX-I and Anti-AUX-II Anti-Drug Antibodies (ADAs) After CCH Treatment | Serum samples were analyzed for anti-AUX-I clostridial class I collagenase of ADAs and anti-AUX-II Clostridial class II collagenase of ADAs. The number of participants who developed anti-AUX-I and anti-AUX-II ADAs (positive ADA result) are reported. | End of Study (Day 28) | 
| Number of Participants With Anti-AUX-I and Anti-AUX-II Neutralizing Antibodies (NAbs) After CCH Treatment | Serum samples were analyzed for anti-AUX-I and Anti-AUX-II Nabs. The number of participants who developed anti-AUX-I and Anti-AUX-II NAbs (positive NAb results) are reported. Neutralizing antibodies were only tested from ADA positive participants. | End of Study (Day 28) |