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

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

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.

Study Overview

• Status: Completed
• Conditions: Laxity; Skin; Cellulite; Edematous Fibrosclerotic Panniculopathy
• Intervention / Treatment: Drug: collagenase clostridium histolyticum

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Endo Clinical Trial Site #3
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Endo Clinical Trial Site #2
  • New York
    • New York, New York, United States, 10021
      • Endo Clinical Trial Site #1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Have a body mass index of 18 to <29.9 kilograms/square meters

2. Have either both buttocks or both posterolateral thighs with:

   1. Score of 2 or 3 (mild or moderate cellulite) as reported by the investigator using the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS)
   2. 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
3. Have a negative pregnancy test or be of non-childbearing potential
4. Be willing and able to cooperate with the requirements of the study
5. 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:

1. Has a history of hypersensitivity or allergy to collagenase or any other excipients of CCH.
2. 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).
3. 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).
4. 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.
5. 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.
6. Is pregnant and/or is breast-feeding or plans to become pregnant and/or to breast-feed during the course of the study.
7. Has a history of scarring due to keloids or abnormal wound healing.
8. Has local (in areas to be treated) conditions (thrombosis, vascular disorder, active infection/inflammation, active cutaneous alteration, tattoo/mole) that restricts study participation
9. Has history of drug or alcohol abuse within the 5 years prior to the Screening Visit.

10. 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

11. Has used or intends to use any of the local application/therapies/injections/procedures that restricts study participation.
12. Has any other condition(s) that, in the investigator's opinion, might indicate the participant to be unsuitable for the study.
13. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Uniform 0.1-milliliters (mL) 1-Aliquot Grid Injection Technique (Buttock); 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; Delivered via uniform grid injection techniques.; Other Names: EN3835; CCH
Active Comparator: Uniform 0.3-mL 2-Aliquot Grid Injection Technique (Buttock); Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area)	Drug: collagenase clostridium histolyticum; Delivered via uniform grid injection techniques.; Other Names: EN3835; CCH
Active Comparator: Uniform 0.1-mL 1-Aliquot Grid Injection Technique (Thigh); Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area)	Drug: collagenase clostridium histolyticum; Delivered via uniform grid injection techniques.; Other Names: EN3835; CCH
Active Comparator: Uniform 0.3-mL 2-Aliquot Grid Injection Technique (Thigh); Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area)	Drug: collagenase clostridium histolyticum; Delivered via uniform grid injection techniques.; Other Names: EN3835; CCH

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: David Hernandez, Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): August 30, 2021
• Study Completion (Actual): September 24, 2021

Study Registration Dates

• First Submitted: October 2, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: August 30, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Manifestations; Cellulite
• Other Study ID Numbers: EN3835-224

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (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