Safety and Effectiveness of EN3835 in the Treatment of EFP in Women

A Phase 2 Open-Label Study of EN3835 In The Treatment of Edematous Fibrosclerotic Panniculopathy

An open-label study of safety and effectiveness of EN3835 in the treatment of cellulite in adult women.

Study Overview

• Status: Completed
• Conditions: Cellulite; Edematous Fibrosclerotic Panniculopathy
• Intervention / Treatment: Biological: Collagenase Clostridium Histolyticum

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Endo Clinical Trial Site #1
  • California
    • Huntington Beach, California, United States, 92647
      • Endo Clinical Trial Site #2
    • San Diego, California, United States, 92121
      • Endo Clinical Trial Site #3
    • Santa Monica, California, United States, 90404
      • Endo Clinical Trial Site #4
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Endo Clinical Trial Site #5
    • Tampa, Florida, United States, 33626
      • Endo Clinical Trial Site #6
    • West Palm Beach, Florida, United States, 33401
      • Endo Clinical Trial Site #7
  • Georgia
    • Alpharetta, Georgia, United States, 30022
      • Endo Clinical Trial Site #8
  • New York
    • New York, New York, United States, 10003
      • Endo Clinical Trial Site #9
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Endo Clinical Trial Site #10
  • Texas
    • Austin, Texas, United States, 78746
      • Endo Clinical Trial Site #11

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Voluntarily sign and date an informed consent agreement
2. Be a female ≥18 years of age

3. At Screening visit, have at least 2 bilateral quadrants with each quadrant having:

   1. a score of 2 (mild) or greater as reported by the Investigator (CR-PCSS), and
   2. a Hexsel CSS score no greater than 13

4. At Day 1 visit, have assigned bilateral quadrants with each quadrant having:

   1. a score of 2 (mild) or greater as reported by the Investigator (CR-PCSS), and
   2. a Hexsel CSS score no greater than 13
5. Be willing to apply sunscreen to the assigned treatment quadrants before each exposure to the sun while participating in the study (i.e., Screening through end of study)
6. Be judged to be in good health, based upon the results of a medical history, physical examination, and laboratory profile at Screening
7. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test before injection of study drug and be using a stable and effective contraception method (e.g., 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
8. Be willing and able to cooperate with the requirements of the study
9. Be able to read, complete and understand the patient-reported outcomes rating instruments in English

Exclusion Criteria:

1. Has any of the following systemic conditions:

   1. Coagulation disorder
   2. Evidence or history of malignancy (other than excised basal-cell carcinoma) unless there has been no recurrence in at least 5 years
   3. History of keloidal scarring or abnormal wound healing
   4. Concurrent diseases or conditions that might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the subject's well-being. Any questions about concurrent diseases should be discussed with the Medical Monitor.
   5. Evidence of clinically significant abnormalities on physical examination, vital signs, electrocardiogram (ECG), or clinical laboratory values.

2. Has any of the following local conditions in the area to be treated:

   1. History of lower extremity thrombosis or post-thrombosis syndrome
   2. Vascular disorder (e.g., varicose veins, telangiectasia) in area to be treated
   3. Inflammation or active infection
   4. Active cutaneous alteration including rash, eczema, psoriasis, or skin cancer
   5. Has a tattoo and/or a mole located within 2 cm of the site of injection

3. Requires the following concomitant medications before or during participation in the trial:

   a. Anticoagulant or antiplatelet medication or has received anticoagulant or antiplatelet medication (except for ≤150 mg aspirin daily) within 7 days before injection of study drug

4. Has used any of the following for the treatment of EFP on the legs or buttock within the timelines identified below or intends to use any of the following at any time during the course of the study:

   1. Liposuction in the areas of the body selected for treatment during the 12-month period before injection of study drug
   2. Injections (eg, mesotherapy); radiofrequency device treatments; laser treatment; buttock and/or thigh implant treatment, or surgery (including subcision and/or powered subcision) within the assigned treatment quadrants during the 12-month period before injection of study drug
   3. Endermologie or similar treatments within the assigned treatment quadrants during the 6 month period before injection of study drug
   4. Massage therapy within the assigned treatment quadrants during the 3-month period before injection of study drug
   5. Creams (eg, Celluvera™, TriLastin®) to prevent or mitigate EFP within the assigned treatment quadrants during the 2-week period before injection of study drug
5. Is presently nursing or providing breast milk
6. Intends to become pregnant during the study
7. Intends to initiate an intensive sport or exercise program during the study
8. Intends to initiate a weight reduction program during the study
9. Intends to use tanning spray or tanning booths during the study
10. Has received an investigational drug or treatment within 30 days before injection of study drug
11. Has a known systemic allergy to collagenase or any other excipient of study drug
12. Has received any collagenase treatments at any time prior to treatment
13. Was a subject in a previous cellulite clinical trial of collagenase clostridium histolyticum (CCH) : AUX-CC-830, AUX-CC-831, EN3835-102, EN3835-104, EN3835-201, and/or EN3835-202
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: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EN3835 Active; EN3835 0.84mg (Collagenase Clostridium Histolyticum)	Biological: Collagenase Clostridium Histolyticum; During 3 treatment visits 12 injections will be given per treatment area; Other Names: Xiaflex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 2-level Responders	Percentage of responders defined as participants with an improvement in cellulite severity from baseline of at least 2-levels of severity of at least one buttock (left or right) on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) with ratings ranging from "0" (None) to "4" (Severe). A 2-level responder is a participant with a reduction in severity of at least 2-levels from Baseline at that particular visit. Number of participants analyzed is determined by observed participants at each visit.	Day 22, 43, 90, and 180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) 1-level Responders	Percentage of responders defined as participants with an improvement in cellulite severity from baseline of at least 1-level of severity of at least one buttock (left or right) on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) with ratings ranging from "0" (None) to "4" (Severe). A 1-level responder is a participant with a reduction in severity of at least 1-level from Baseline at that particular visit. Percentages are based on the observed counts. Number of participants analyzed is determined by observed participants at each visit.	Day 22, 43, 90, and 180
Subject Satisfaction With Cellulite Treatment Assessment at End of Study	At Day 180, participants rated their satisfaction with cellulite treatment using the 5-point subject satisfaction scale. Ratings range from Very Satisfied with Treatment (2), Satisfied with Treatment (1), Neither Dissatisfied nor Satisfied with Treatment (0), Dissatisfied with Treatment (-1), and Very Dissatisfied with Treatment (-2). Percentages are based on the observed counts.	Day 180

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Anti-AUX-I Serum Antibody by Visit	Percent of participants that are seropositive. Descriptive statistics were based on log10 transformation of titer levels. Percentages were based on the number of subjects who had immunogenicity lab samples drawn at the visit. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.	Day 1 to Day 180
Overall Anti-AUX-I Antibody Log Titer Levels by Visit	Descriptive statistics were based on log10 transformation of titer levels. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.	Day 1 to Day 180
Overall Anti-AUX-II Serum Antibody by Visit	Percent of participants that are seropositive. Descriptive statistics were based on log10 transformation of titer levels. Percentages were based on the number of subjects who had immunogenicity lab samples drawn at the visit. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.	Day 1 to Day 180
Overall Anti-AUX-II Antibody Log Titer Levels by Visit	Descriptive statistics were based on log10 transformation of titer levels. Overall number of participants analyzed is determined by the number of participants in the study. At each visit, the number of participants analyzed is determined by observed participants that had a seropositive sample.	Day 1 to Day 180
Anti-AUX-I Neutralizing Antibodies by Visit	A subset of all CCH Treated participants who had positive binding antibody titer levels were tested for the presence or absence of Neutralizing Antibodies. Overall Number of Participants Analyzed is determined by the number of participants in the highest and lowest quartiles at Day 90 (Q1 and Q4) of seropositive participants at each of two visits (Day 90 and Day 180).	Day 1 to Day 180
Anti-AUX-II Neutralizing Antibodies by Visit	A subset of all CCH Treated participants who had positive binding antibody titer levels were tested for the presence or absence of Neutralizing Antibodies. Overall Number of Participants Analyzed is determined by the number of participants in the study. Number of Participants Analyzed is determined by observed participants that had a seropositive sample at each visit and the antibody level at Day 71 in Q1 and Q4.	Day 1 to Day 180

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: Mike McLane, PhD, Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2017
• Primary Completion (Actual): September 5, 2018
• Study Completion (Actual): September 5, 2018

Study Registration Dates

• First Submitted: October 31, 2017
• First Submitted That Met QC Criteria: October 31, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 7, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Manifestations; Edema; Cellulite
• Other Study ID Numbers: EN3835-205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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