Safety and Efficacy Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease (JOINT-I)

A Phase 3, Open-Label Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Advanced Dupuytren's Disease

This was a Phase 3, 9-month, open-label study conducted in the United States. Subjects with a diagnosis of advanced Dupuytren's disease in a metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint that resulted in a fixed flexion deformity of at least one finger, other than the thumb, that was at least 20° as measured by finger goniometry and was suitable for evaluation and injection were enrolled.

This study was designed to be part of the larger clinical program, for adult patients with Dupuytren's contracture with a palpable cord, where the data from 2 pivotal Placebo-Controlled studies (AUX-CC-857 (NCT00528606) and AUX-CC-859 (NCT00533273)) and 7 non-pivotal studies were evaluated.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85050
      • HOPE Research Institute
    • Tucson, Arizona, United States, 85172
      • Tucson Orthopedic Institute, P.C.
  • California
    • Burbank, California, United States, 91505
      • Providence Clinical Research
  • Illinois
    • Effingham, Illinois, United States, 62401
      • Southern Illinois Hand Center, S.C.
    • Rockford, Illinois, United States, 61107
      • Rockford Orthopedic Associates, Ltd.
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • The Indiana Hand Center
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Pri Via
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • St. Alexius Medical Center
  • Ohio
    • Mayfield, Ohio, United States, 44143
      • David R. Mandel, Inc.
  • Oregon
    • Portland, Oregon, United States, 97225
      • St. Vincent Medical Center
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16550
      • Hamot Center for Clinical Research
  • Tennessee
    • Clarksville, Tennessee, United States, 37043
      • Alpha Clinical Research
  • Texas
    • Houston, Texas, United States, 77034
      • Accurate Clincal Research
    • Houston, Texas, United States, 77004
      • The Rheumatic Disease Clinic of Houston

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:

• Subjects with a diagnosis of advanced Dupuytren's disease, with a fixed flexion deformity of at least one finger, other than the thumb, that had a contracture at least 20°, but not greater than 100° for MP (80° for PIP) joints, caused by a palpable cord.
• Had a positive "table top test," defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top.
• Were naïve to AA4500 treatment or had received one or two injections of AA4500 for the treatment of advanced Dupuytren's disease in Auxilium Studies AUX-CC-851, AUX-CC-853, or AUX-CC-855.
• Were judged to be in good health.

Exclusion Criteria:

• Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands.
• Had received treatment for advanced Dupuytren's disease within 90 days of enrollment on the joint selected for the initial injection of AA4500, including surgery (fasciectomy or surgical fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon.
• Had a known recent history of stroke, bleeding, a disease process that affected the hands, or other medical condition, which in the investigator's opinion, would make the subject unsuitable for enrollment in 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: AA4500 0.58 mg	Biological: collagenase clostridium histolyticum; Up to five injections of AA4500 into cord(s) of the affected hand(s). Each injection was separated by at least 30 days.; Other Names: XIAFLEX®; AA4500

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in Contracture to 5° or Less	The Primary Outcome Measure is the percentage of joints that were successfully treated where "successfully treated" was defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection	Within 30 days after the last injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Improvement After the Last Injection	Clinical Improvement is defined as >=50% percent reduction from baseline in degree of contracture within 30 days after injection.	Baseline; within 30 days after last injection
Percent Reduction From Baseline Contracture After the Last Injection	Percent change in degree of contracture measured as 100*(baseline contracture -last available post-injection contracture)/baseline contracture)	Baseline, within 30 days after last injection
Change From Baseline Range of Motion After the Last Injection	Change in degree of range of motion measured as last available post-injection range of motion - baseline range of motion.	Baseline, 30 days after last injection
Time to Reach Clinical Success	Clinical success is defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection, displayed in post-injection timepoint categories.	First evaluation visit on which clinical success is achieved through the Day 30 evaluation
Clinical Success After the First Injection	Clinical Success is defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection.	Within 30 days after first injection
Clinical Improvement After the First Injection	Clinical Improvement is defined as >=50% reduction from baseline in the degree of contracture within 30 days after the first injection	Baseline; within 30 days after first injection
Percent Reduction From Baseline Contracture After the First Injection	Percent change in degree of contracture is measured as 100* (baseline contracture- last available post-injection contracture)/baseline contracture.	Baseline; within 30 days after first injection
Change From Baseline Range of Motion After the First Injection	Change in degree of range of motion measured as last available post-injection range of motion-baseline range of motion.	Baseline; within 30 days after first injection

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: Veronica Urdaneta, MD, Endo Pharmaceuticals

Publications and helpful links

Helpful Links

• XIAFLEX Prescribing Information

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: September 11, 2007
• First Submitted That Met QC Criteria: September 11, 2007
• First Posted (Estimate): September 12, 2007

Study Record Updates

• Last Update Posted (Actual): December 2, 2017
• Last Update Submitted That Met QC Criteria: October 26, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Musculoskeletal Diseases; Connective Tissue Diseases; Muscular Diseases; Neoplasms, Connective Tissue; Neoplasms, Fibrous Tissue; Fibroma; Contracture; Dupuytren Contracture
• Other Study ID Numbers: AUX-CC-856