Retreatment of Recurrent Dupuytren's Contractures

Retreatment of Recurrent Contractures in Joints Effectively Treated With AA4500 (Collagenase Clostridium Histolyticum [XIAFLEX®/XIAPEX®]) in an Auxilium-sponsored Phase 3 Study in the United States, Australia, and Europe

The objectives of this study are to assess the safety and efficacy of AA4500 in the retreatment of recurrent contractures in joints that were effectively treated with AA4500 in a previous Auxilium-sponsored Phase 3 study.

Study Overview

• Status: Completed
• Conditions: Dupuytren's Disease
• Intervention / Treatment: Biological: Collagenase clostridium histolyticum

Detailed Description

Open-label, Phase 4 study in subjects who are currently participating in the long-term follow-up study (ie, AUX-CC-860) in the United States, Australia, or Europe and who have recurrence of contracture (ie, joint contracture increases by at least 20 degrees compared with the Day 30 value after the last injection in a Phase 3 Auxilium-sponsored study and a palpable cord present) in a joint that was effectively treated (ie, reduction in contracture to 5 degrees or less 30 days after the last injection) with AA4500 in a Phase 3 Auxilium-sponsored study.

Subjects who experience recurrence of contracture in one or more effectively treated joints may be enrolled in this retreatment study after the investigator determines subject eligibility and after informed consent has been obtained. The investigator will treat the cord affecting the recurrent joint with up to three injections. Only one recurrent joint will be treated in this study.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Kippa Ring, Queensland, Australia, 4021
      • Peninsula Private Hospital
    • Sherwood, Queensland, Australia, 4075
      • AusTrials Sherwood
  • Victoria
    • Malvern East, Victoria, Australia, 3145
      • Emeritus Research
• Sweden
  • SE
    • Uppsala, SE, Sweden, SE-751
      • Uppsala Akademiska University Hospital
• United Kingdom
  • GB
    • Derby, GB, United Kingdom, DE22 3NE
      • Pulvertaft Hand Center
    • Newcastle, GB, United Kingdom, NE1 4LP
      • Newcastle upon Tyne Hospitals
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85050
      • HOPE Research Institute
  • Illinois
    • Rockford, Illinois, United States, 61107
      • Rockford Orthopedic Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • The Indiana Hand to Shoulder Center
  • Michigan
    • Marquette, Michigan, United States, 49855
      • Marquette General Health System
  • New York
    • New York, New York, United States, 10021
      • East River Professional Building
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Health Reserarch Institute
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Hand Microsurgery and Reconstructive Orthopaedics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provide written informed consent
2. Be currently participating in the AUX-CC-860 follow-up study

3. Have at least one joint with all of the following:

   • The joint was effectively treated (had a correction to 5 degrees or less at the Day 30 evaluation after the last injection of AA4500) in a previous Auxilium Phase 3 study
   • The effectively treated joint has an increase in contracture of at least 20 degrees compared with the Day 30 value after the last injection of AA4500 in a previous Auxilium Phase 3 study
   • A palpable cord is present in the joint to be treated
4. Be able to comply with the study visit schedule as specified in the protocol

Exclusion Criteria:

1. Is a pregnant or lactating female or female intending to become pregnant during the study
2. Has hypersensitivity to AA4500 or any of the AA4500 excipients
3. Is currently receiving or plans to receive anticoagulant medication or has received anticoagulant medication (except for equal to or less than 150 mg aspirin daily and over-the-counter nonsteroidal antiinflammatory drugs [NSAIDs]) within 7 days before injection of AA4500

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: XIAFLEX/XIAPEX MP Joint; Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the metacarpophalangeal (MP) joint cord	Biological: Collagenase clostridium histolyticum; up to three 0.58 mg injections; Other Names: AA4500; XIAFLEX; XIAPEX
EXPERIMENTAL: XIAFLEX/XIAPEX PIP Joint; Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the proximal interphalangeal (PIP) joint cord	Biological: Collagenase clostridium histolyticum; up to three 0.58 mg injections; Other Names: AA4500; XIAFLEX; XIAPEX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Success	Clinical success defined as reduction in fixed-flexion contracture to less than or equal to 5 degrees 30 days after the last injection of AA4500	30 days after last injection
Percent Change From Baseline in Degree of Contracture	Change in fixed-flection contracture measured in degrees where a decrease of 100% would correspond to a reduction in contracture to 0 degrees	Baseline and 30 days after last injection
Change in Range of Motion	Range of motion defined as difference between full flexion angle and full extension angle expressed in degrees	Baseline and 30 days after last injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physician Global Assessment of Improvement	Physician global assessment of change (improvement) in subject's Dupuytren's contracture	30 days after last injection
Subject Global Assessment of Satisfaction	Subject global assessment of overall treatment satisfaction	30 days after last injection
Recurrence of Contracture	Recurrence of contracture in the joint at day 365 that was successfully treated 30 days after last injection assessed. Recurrence was defined as 20 degree or greater increase of contracture of the treated joint at day 365 or medication intervention of the treated joint between the 2 time points.	Day 365

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): October 1, 2013
• Study Completion (ACTUAL): October 1, 2013

Study Registration Dates

• First Submitted: December 17, 2011
• First Submitted That Met QC Criteria: December 21, 2011
• First Posted (ESTIMATE): December 23, 2011

Study Record Updates

• Last Update Posted (ACTUAL): October 5, 2017
• Last Update Submitted That Met QC Criteria: September 7, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Dupuytren's disease; XIAFLEX; XIAPEX; contracture
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Joint Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Muscular Diseases; Neoplasms, Connective Tissue; Neoplasms, Fibrous Tissue; Fibroma; Contracture; Dupuytren Contracture
• Other Study ID Numbers: AUX-CC-862