Histopathology Following CCH Injection

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

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

Study Overview

• Status: Completed
• Conditions: Characteristics of Subcutaneous Tissue
• Intervention / Treatment: Drug: Collagenase Clostridium Histolyticum Single Injection Technique; Drug: Collagenase Clostridium Histolyticum Multiple Injection Technique

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Montclair, New Jersey, United States, 07042
      • Endo Clinical Trial Site #1
  • New York
    • New York, New York, United States, 10021
      • Endo Clinical Trial Site #2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Be adequately informed and understand the nature and risks of the study and be able to provide consent.
2. Be undergoing planned elective abdominoplasty.
3. Be willing to have their tissue donated for evaluation.
4. Be judged to be in good health.
5. Have a negative pregnancy test.
6. Be willing and able to cooperate with the requirements of the study.

Exclusion Criteria:

1. 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).
2. Has systemic conditions (coagulation disorders, malignancy, keloidal scar, abnormal wound healing) that restricts study participation.
3. Has local (in the areas to be treated) conditions (thrombosis, vascular disorder, active infection/inflammation, active cutaneous alteration, tattoo/mole) that restricts study participation.
4. Required use of anticoagulant or antiplatelet medication (except ≤ 150 mg aspirin daily) before or during participation in the trial.
5. Past history of any abdominal surgery, including but not limited to: liposuction, caesarean section, appendectomy, cholecystectomy, or umbilical hernia repair.
6. Has used or intends to use any local applications/therapies/injections/procedures that restricts study participation.
7. Is presently nursing or providing breast milk in any manner.
8. Intends to become pregnant during the study.
9. Intends to initiate an intensive sport or exercise program regimen during the study.
10. Intends to use any tanning spray or tanning booths during the study.
11. Has received any investigational drug or treatment within 30 days prior to first injection of study drug.
12. Has a known systemic allergy to collagenase or any other excipient of study drug.
13. Has received any collagenase treatment at any time prior to treatment in this study.
14. Any other condition(s) that, in the investigator's opinion, might indicate the subject to be unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1: CCH Single Injection Technique; 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; CCH was injected subcutaneously using a single injection technique. Dose per each administration was 0.07 mg.; Other Names: EN3835; CCH
EXPERIMENTAL: Group 2: CCH Single Injection Technique; 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; CCH was injected subcutaneously using a single injection technique. Dose per each administration was 0.07 mg.; Other Names: EN3835; CCH
EXPERIMENTAL: Group 3: CCH Single Injection Technique; 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; CCH was injected subcutaneously using a single injection technique. Dose per each administration was 0.07 mg.; Other Names: EN3835; CCH
EXPERIMENTAL: Group 4: CCH Multiple Injection Technique; 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; CCH was injected subcutaneously using a multiple injection technique. Dose per each administration was 0.0653 mg.; Other Names: EN3835; CCH
EXPERIMENTAL: Group 5: CCH Multiple Injection Technique; 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; CCH was injected subcutaneously using a multiple injection technique. Dose per each administration was 0.0653 mg.; Other Names: EN3835; CCH
EXPERIMENTAL: Group 6: CCH Multiple Injection Technique; 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; CCH was injected subcutaneously using a multiple injection technique. Dose per each administration was 0.0653 mg.; Other Names: EN3835; CCH

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 20, 2019
• Primary Completion (ACTUAL): September 23, 2020
• Study Completion (ACTUAL): October 26, 2020

Study Registration Dates

• First Submitted: January 2, 2020
• First Submitted That Met QC Criteria: January 17, 2020
• First Posted (ACTUAL): January 22, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 12, 2022
• Last Update Submitted That Met QC Criteria: March 17, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: EN3835-213

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No