Long-Term Study of EN3835 (CCH-aaes) in Edematous Fibrosclerotic Panniculopathy (Cellulite)

A Phase 3b, Open-Label, Long-Term Study to Evaluate the Safety and Temporal Pattern of Response of EN3835 in the Treatment of Edematous Fibrosclerotic Panniculopathy

A Phase 3b, Open-Label Extension Study to evaluate safety and how long response of EN3835 (Collagenase Clostridium Histolyticum [CCH]-aaes) lasts in the treatment of Cellulite.

Study Overview

• Status: Completed
• Conditions: Cellulite; Edematous Fibrosclerotic Panniculopathy
• Intervention / Treatment: Biological: CCH-aaes; Other: Observation

Detailed Description

This study included participants who completed EN3835-302 (NCT03428750) or EN3835-303 (NCT03446781) double-blind parent studies. The first part of this study consisted of an observational period conducted in a blinded fashion and where no treatments were administered between Day 71 of the parent studies and Day 180 in this Open-label extension study. Once these participants were unblinded at Day 180, only participants who received active CCH-aaes in the parent studies remained in this study and those who received placebo in the parent studies were not eligible to continue in the Open-label study. Assessments made at the Day 71/(End of Study [EOS]) visit of the parent studies served as initial screening assessments for this study.

In the Open-label Phase of the study, all participants who qualified for, and opted for, retreatment were administered CCH-aaes at 3 treatment sessions at 21-day intervals.

• Study Type: Interventional
• Enrollment (Actual): 483
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Glendale, Arizona, United States, 85308
      • Endo Clinical Trial Site #3
    • Scottsdale, Arizona, United States, 85258
      • Endo Clinical Trial Site #11
  • Arkansas
    • North Little Rock, Arkansas, United States, 72116
      • Endo Clinical Trial Site #41
  • California
    • Encinitas, California, United States, 92024
      • Endo Clinical Trial Site #14
    • Long Beach, California, United States, 90806
      • Endo Clinical Trial Site #9
    • Murrieta, California, United States, 92562
      • Endo Clinical Trial Site #35
    • Newport Beach, California, United States, 92663
      • Endo Clinical Trial Site #42
    • Oceanside, California, United States, 92056
      • Endo Clinical Trial Site #17
    • San Diego, California, United States, 92121
      • Endo Clinical Trial Site #39
  • Colorado
    • Greenwood Village, Colorado, United States, 80111
      • Endo Clinical Trial Site #23
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Endo Clinical Trial Site #38
    • Coral Gables, Florida, United States, 33146
      • Endo Clinical Trial Site #8
    • Largo, Florida, United States, 33770
      • Endo Clinical Trial Site #40
    • Miami, Florida, United States, 33137
      • Endo Clinical Trial Site #27
    • Miami, Florida, United States, 33185
      • Endo Clinical Trial Site #36
  • Georgia
    • Snellville, Georgia, United States, 30078
      • Endo Clinical Trial Site #20
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Endo Clinical Trial Site #19
  • Illinois
    • Chicago, Illinois, United States, 60654
      • Endo Clinical Trial Site #34
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Endo Clinical Trial Site #30
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Endo Clinical Trial Site #16
    • New Orleans, Louisiana, United States, 70115
      • Endo Clinical Trial Site #10
    • New Orleans, Louisiana, United States, 70124
      • Endo Clinical Trial Site #25
  • Massachusetts
    • Quincy, Massachusetts, United States, 02169
      • Endo Clinical Trial Site #33
  • Missouri
    • Washington, Missouri, United States, 63090
      • Endo Clinical Trial Site #18
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Endo Clinical Trial Site #4
  • New York
    • Mount Kisco, New York, United States, 10549
      • Endo Clinical Trial Site #24
    • New York, New York, United States, 10016
      • Endo Clinical Trial Site #32
    • New York, New York, United States, 10022
      • Endo Clinical Trial Site #12
    • New York, New York, United States, 10065
      • Endo Clinical Trial Site #15
    • New York, New York, United States, 10075
      • Endo Clinical Trial Site #29
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Endo Clinical Trial Site #26
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Endo Clinical Trial Site #5
  • Texas
    • Austin, Texas, United States, 78759
      • Endo Clinical Trial Site #22
    • Beaumont, Texas, United States, 77701
      • Endo Clinical Trial Site #6
    • Houston, Texas, United States, 77056
      • Endo Clinical Trial Site #13
    • Houston, Texas, United States, 77494
      • Endo Clinical Trial Site #7
    • Pflugerville, Texas, United States, 78660
      • Endo Clinical Trial Site #28
    • San Antonio, Texas, United States, 78229
      • Endo Clinical Trial Site #21
    • Sugar Land, Texas, United States, 77497
      • Endo Clinical Trial Site #37
  • Utah
    • Salt Lake City, Utah, United States, 84101
      • Endo Clinical Trial Site #31
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Endo Clinical Trial Site #1
    • Lynchburg, Virginia, United States, 24501
      • Endo Clinical Trial Site #2

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria

All Participants (Through Day 180):

1. Voluntarily sign and date an informed consent agreement
2. Have participated in and completed the double-blind Phase 3 study EN3835-302 or EN3835-303
3. Be willing to apply sunscreen to the buttocks before each exposure to the sun and/or tanning booths while participating in the study
4. Be judged to be in good health
5. Be willing and able to cooperate with the requirements of the study
6. Be able to read, complete and understand the participant reported outcomes rating instruments in English.

Key Inclusion Criteria for Participants Eligible for Retreatment:

1. Have a negative pregnancy test and using a stable and effective contraception method.

Key Exclusion Criteria

All Participants (Through Day 180):

1. Intends to or has used any of the local applications/therapies/injections/procedures that restricts study participation
2. Intends to use tanning spray or tanning booths during this period
3. Has received or intends to receive an investigational drug or treatment, other than the treatment received in study EN3835-302/303 during this period
4. Any other condition(s) that, in the Investigator's opinion, might indicate the participant to be unsuitable for the study

Additional Exclusion Criteria may apply Post Day 180:

1. Has received any collagenase treatments at any time since completion of the double-blind study (EN3835-302 or EN3835-303).

Key Exclusion Criteria for Participants Eligible for Retreatment:

1. Has systemic conditions (coagulation disorders, malignancy, keloidal scar, abnormal wound healing) that restricts study participation

• Has local (in areas to be treated) conditions (thrombosis, vascular disorder, active infection/inflammation, skin laxity, flaccidity and/or skin sagging, active cutaneous alteration, tattoo/mole) that restricts study participation
• Requires anticoagulant or antiplatelet medication during the study
• Prior to and during the course of retreatment, is nursing or providing breast milk in any manner, intends to become pregnant during the study, or intends to use tanning spray or tanning booths during the study
• Has received an investigational drug or treatment, other than treatment in study EN3835-302/303, within 30 days before retreatment with study drug
• Has a known systemic allergy to collagenase or any other excipient of study drug
• Has received any collagenase treatments at any time since completion of the double-blind study
• Any other condition(s) that, in the Investigator's opinion, might indicate the participant to be unsuitable for retreatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CCH-aaes Treatment in Parent Studies (EN3835-302/303); Participants who received CCH-aaes treatment in EN3835-302/303 were followed for 180 days of observation with no treatment. Participants who were identified as received CCH-aaes in the parent studies following the 180-day Observation Phase and entered the Open-label Phase of the study. Participants in the Open-label Phase who qualified for, and opted for, retreatment were administered CCH-aaes up to 1.68 mg at 3 treatment sessions, at 21-day intervals.	Biological: CCH-aaes; Administered to participants who qualified for, and opted for, retreatment.; Other Names: EN3835; QWO™; Other: Observation; No treatment administered during 180 days of observation.
Other: Placebo Treatment in Parent Studies (EN3835-302/303); Participants who received placebo in the parent studies, were followed for 180 days of observation with no treatment. After Day 180, all participants who received placebo during the double-blind parent studies were discontinued. No treatment was administered.	Other: Observation; No treatment administered during 180 days of observation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was any unfavorable or unintended change in body structure (signs), body function (symptoms), laboratory result, or worsening of a pre-existing condition associated temporally with the use of the study medication whether or not considered related to the study medication. TEAEs were defined as any AEs with a start date equal to or after the date of the first injection. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to Day 1080
Percentage of Participants Who Were Seropositive for Anti-Drug Antibodies (ADAs) After CCH-aaes Treatment	Serum samples were analyzed for ADAs. The percentage of participants who developed ADAs (seropositive results) during the Open-label Phase of the study are reported.	From Day 180 (Open-label Phase) up to Day 1080

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to 2-Level Reduction of Response in Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS)	CR-PCSS and PR-PCSS assess improvement in cellulite severity using a 5-level scale ranging from "0" (None) to "4" (Severe). Time to reduction of response (days) was defined as the number of days from Screening assessment of composite improvement in cellulite severity in PR-PCSS and CR-PCSS to the time at which a 2-level composite worsening of response was observed for the first time.	From Day 180 (Open-label Observation Phase) up to Day 1080
Time to 1-Level Reduction of Response in CR-PCSS and PR-PCSS	CR-PCSS and PR-PCSS assess improvement in cellulite severity using a 5-level scale ranging from "0" (None) to "4" (Severe). Time to reduction of response (days) was defined as the number of days from Screening assessment of composite improvement in cellulite severity in CR-PCSS and PR-PCSS to the time at which 1-level composite worsening of response was observed for the first time.	From Day 180 (Open-label Observation Phase) up to Day 1080
Time to Complete Loss of Response in CR-PCSS and PR-PCSS	CR-PCSS and PR-PCSS assess improvement in cellulite severity using a 5-level scale ranging from "0" (None) to "4" (Severe). Complete loss of response is defined as both CR-PCSS and PR-PCSS ratings returned to the baseline severity of the double-blind study or worse for both the buttocks. Time to complete loss of response (days) was defined as the number of days from Screening assessment of composite improvement in cellulite severity in CR-PCSS and PR-PCSS to the time at which complete loss of response was observed for the first time.	From Day 180 (Open-label Observation Phase) up to Day 1080

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: Karen Chajko, Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2018
• Primary Completion (Actual): October 8, 2021
• Study Completion (Actual): October 8, 2021

Study Registration Dates

• First Submitted: April 25, 2018
• First Submitted That Met QC Criteria: May 15, 2018
• First Posted (Actual): May 16, 2018

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: August 15, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Manifestations; Edema; Cellulite
• Other Study ID Numbers: EN3835-304

Drug and device information, study documents

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