EN3835 for the Treatment of Edematous Fibrosclerotic Panniculopathy (Commonly Known as Cellulite)

The study will evaluate the safety, effectiveness, and immunogenicity of EN3835 in the treatment of adult women with Edematous Fibrosclerotic Panniculopathy (Commonly known as Cellulite).

Study Overview

• Status: Completed
• Conditions: Cellulite; Edematous Fibrosclerotic Panniculopathy
• Intervention / Treatment: Biological: Placebo Comparator; Biological: COLLAGENASE CLOSTRIDIUM HISTOLYTICUM

• Study Type: Interventional
• Enrollment (Actual): 375
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90210
      • Clinical Testing of Beverly Hills
    • Murrieta, California, United States, 92562
      • Dermatology Specialists, Inc
    • Oceanside, California, United States, 92056
      • Dermatology Specialists, Inc
    • San Diego, California, United States, 92121
      • Dermatology Cosmetic Laser Medical Associates of LaJolla, Inc
  • Florida
    • Clearwater, Florida, United States, 33756
      • Olympian Clinical Research
    • Coral Gables, Florida, United States, 33146
      • Skin Research Institute LLC
    • West Palm Beach, Florida, United States, 33401
      • Research Institute of the Southeast
  • Missouri
    • Washington, Missouri, United States, 10075
      • Mercy Health Research
  • New York
    • New York, New York, United States, 10075
      • Sadick Research Group
    • New York, New York, United States, 10065
      • Bass Plastic Surgery, PLLC
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Dermatology Consulting Services
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Tennessee Clinical Research Center
  • Texas
    • Pflugerville, Texas, United States, 78660
      • Austin Institute for Clinical Research
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research Center LLC
    • Lynchburg, Virginia, United States, 24501
      • The Education & Research Foundation
  • Washington
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Be a female ≥18 years of age

• At Screening visit, have at least 1 quadrant with:

  • a score of 3 or 4 (moderate or severe) as reported by the subject (PR- PCSS), and
  • a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS), and
  • a Hexsel CSS score no greater than 13

• At Day 1 visit, have an assigned quadrant with:

  • a score of 3 or 4 (moderate or severe) as reported by the subject (PR-PCSS), and
  • a score of 3 or 4 (moderate or severe) as reported by the Investigator (CR-PCSS), and
  • a Hexsel CSS score no greater than 13
• Be willing to apply sunscreen to the selected treatment quadrant before each exposure to the sun while participating in the study (ie, screening through end of study).
• Be judged to be in good health, based upon the results of a medical history, physical examination, and laboratory profile at screening
• Have a negative urine pregnancy test at screening and be using an effective contraception method (eg, 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.
• Be willing and able to cooperate with the requirements of the study
• Voluntarily sign and date an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee/Human Research Ethics Committee (IRB/IEC/HREC).
• Be able to read, complete and understand the Patient Reported Outcomes rating instruments in English

Exclusion Criteria:

• Has any of the following conditions:

  • Thyroid disease, unless controlled with medication for ≥6 months
  • Uncontrolled diabetes mellitus, as determined by the Investigator
  • Uncontrolled hypertension, as determined by the Investigator
  • Vascular disorder (eg, phlebitis or varicose veins) in area to be treated
  • Cushing's disease and/or use of systemic corticosteroids at a total daily dose greater than 5 mg prednisone (or equivalent)
  • History of lower extremity thrombosis or post-thrombosis syndrome
  • Documented autoimmune disorder such as lupus erythematosus, rheumatoid arthritis
  • Inflammation or active infection in area to be treated
  • Active cutaneous alteration in area to be treated including rash, eczema, psoriasis or skin cancer
  • History of keloidal scarring or abnormal wound healing
  • Coagulation disorder
  • Taking a medication for chronic anticoagulation (except for ≤150 mg aspirin daily)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EN3835 Active; EN3835 0.84 mg (Collagenase Clostridium Histolyticum). Each subject can receive up to three treatment sessions. Each treatment session will be separated by approximately 21 days.	Biological: COLLAGENASE CLOSTRIDIUM HISTOLYTICUM; Injectable intervention; Other Names: Xiaflex
Placebo Comparator: EN3835 Placebo; Placebo	Biological: Placebo Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Composite Responders of at Least 2-Level Improvement of Severity	Percentage of composite responders defined as subjects with an improvement from baseline of at least 2-levels of severity on each, the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), at Day 71 in the ITT population. The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement on each scale for example would represent a change from a 4 (severe) to a 2 (mild). In order to be considered a responder a subject needs to have at least a 2-level improvement on both scales.	Baseline, Day 71

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Composite Responders of at Least 1-Level Improvement of Severity	Percentage of composite responders defined as subjects with improvement from baseline of at least 1-level of severity on each, the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), at Day 71 in the ITT population. The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 1-level improvement on each scale for example would represent a change from a 4 (severe) to a 3 (moderate). In order to be considered a responder a subject needs to have at least a 1-level improvement on both scales.	Baseline, Day 71
CR-PCSS Responder Analysis: 2-Levels of Severity	Percentage of subjects with improvement from baseline of at least 2-levels of severity on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) at Day 71.The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement would be for example a change from 4 (severe) to 2 (mild).	Baseline, Day 71
CR-PCSS Responder Analysis: 1-Level of Severity	Percentage of subjects with improvement from baseline of at least 1-level of severity on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) at Day 71.The CR-PCSS is a photonumeric scale that was used by the investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 1-level improvement would be for example a change from 4 (severe) to 3 (moderate).	Baseline, Day 71
CR-PCSS Change From Baseline	The CR-PCSS is a photonumeric scale that was used by the investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). Change is Day 71 study visit rating minus baseline visit; negative values indicate a lessening in cellulite severity.	Baseline, Day 71
PR-PCSS Responder Analysis: 2-Levels of Severity	Percentage of subjects with improvement from baseline of at least 2-levels of severity on the subject-rated Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) at Day 71.The PR-PCSS is a photonumeric scale that was used by the subject to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement would be for example a change from 4 (severe) to 2 (mild).	Baseline, Day 71
PR-PCSS Responder Analysis: 1-Level of Severity	Percentage of subjects with improvement from baseline of at least 1-level of severity on the subject-rated Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) at Day 71.The PR-PCSS is a photonumeric scale that was used by the subject to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 1-level improvement would be for example a change from 4 (severe) to 3 (moderate).	Baseline, Day 71
PR-PCSS Change From Baseline	The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). Change is Day 71 study visit rating minus baseline visit; negative values indicate a lessening in cellulite severity.	Baseline, Day 71
Investigator Assessment of Improvement Based on the Investigator Global Aesthetic Improvement Scale (I-GAIS)	On Day 71, the Investigator determined the degree of improvement from baseline in the treated area using the 7-point I-GAIS. Ratings could be improved (+1), much improved (+2), or very much improved (+3), or no change (0), or worse (-1), much worse (-2) or very much worse (-3).	Day 71
Subject Assessment of Improvement Based on the Subject Global Aesthetic Improvement Scale (S-GAIS)	At Day 71, subjects were asked to rate their opinion of the overall improvement of their treated area using the 7-point S-GAIS. Ratings could be improved (+1), much improved (+2), or very much improved (+3), or no change (0), or worse (-1), much worse (-2) or very much worse (-3)	Day 71
Subject Satisfaction Assessment Based on the the Subject Satisfaction Scale	At Day 71, subjects were asked to rate their satisfaction with cellulite treatment using the 5-point subject satisfaction scale. Ratings could be satisfied (+1), very satisfied (+2), neither satisfied nor dissatisfied (0), or dissatisfied (-1), very dissatisfied (-2).	Day 71
Change in the Hexsel Cellulite Severity Scale (CSS) Total Score	Investigator used the Hexsel CSS to assess the severity of cellulite. The total score could range from 0 (no cellulite) to 15 (extremely severe cellulite). Negative change in Hexsel CSS total score indicates an improvement in cellulite severity	Baseline, Day 71

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: March 10, 2016
• First Submitted That Met QC Criteria: March 25, 2016
• First Posted (Estimate): March 31, 2016

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: October 4, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Manifestations; Edema; Cellulite
• Other Study ID Numbers: EN3835-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes