Collagenase in the Treatment of Dupuytrens Disease

Double-blind, Randomized Placebo Controlled Study of the Relative Safety and Efficacy of Collagenase Therapy in the Treatment of Residual-type Dupuytren's Disease.

The purpose of the study is to determine if collagenase will reduce the degree of contracture in the primary joint in subjects with Dupuytren's disease.

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 and AUX-CC-859) and 7 non-pivotal studies were evaluated.

Study Overview

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

Detailed Description

In a random, placebo controlled, double blind study, collagenase injection therapy will be investigated for it's ability to disrupt the Dupuytren's cord.

Resultant cord disruption may obviate the need for patients to have surgery to correct the finger flexion contractures of Dupuytren's disease.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Hospital and Mediacl Center

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 were at least 18 years of age, of either sex or any race.
• Subjects had residual Dupuytren's disease with a fixed-flexion deformity of the finger(s) of at least 20 degrees or greater, caused by a palpable cord.
• Subjects had a positive "table-top test" defined as the inability to simultaneously place their affected finger(s) and palm flat against a table top.
• Subjects must have been willing to participate in and complete the study, and comply with its procedures by signing an IRB approved written consent form.
• Subjects must have been able to understand and adhere to the visit schedule. They must have been able to follow study procedures and instructions, and have agreed to report concomitant medications and adverse events accurately and consistently.
• Women of childbearing potential must have agreed to use an acceptable method of birth control or must have been surgically sterilized (hysterectomy or tubal ligation). Women of childbearing age had a urine pregnancy test on Day 0 (day of injection) prior to the injection.

Exclusion Criteria

• Women who were nursing or who were pregnant (as evidenced by a positive urine pregnancy test at the time of enrollment).
• Subjects who had participated in an investigational drug trial within 30 days of enrollment in this study.
• Subjects who had received surgery for Dupuytren's disease within 30 days of enrollment in this study.
• Subjects who had a known allergy to AA4500 or any of the inactive ingredients in the AA4500 injection.
• Subjects who had a known allergy to doxycycline.
• Subjects who had a medical condition that would have made them unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Biological: collagenase clostridium histolyticum; Subjects could have received up to three injections of AA4500/placebo into the cord of the affected hand. Each injection was separated by at least 30 days. Individual cords may have received up to a maximum of three injections.; Other Names: XIAFLEX®; AA4500
Experimental: AA4500 0.58 mg	Biological: collagenase clostridium histolyticum; Subjects could have received up to three injections of AA4500/placebo into the cord of the affected hand. Each injection was separated by at least 30 days. Individual cords may have received up to a maximum of three injections.; Other Names: XIAFLEX®; AA4500

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome Measure is Reduction of Flexion Contracture of the Primary Joint.	The Primary Outcome Measure for patients treated with AA4500 is the percentage of 23 joints that were successfully treated where "successfully treated" was defined as reduction in contracture to 5° or less. The Primary Outcome Measure for placebo treated patients is the percentage of 12 joints that were successfully treated where "successfully treated" was defined as reduction in contracture to 5° or less.	30 days after the last injection

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Reduction From Baseline Contracture After the Last Injection	30 days after last treatment to the primary joint
Percent Change From Baseline Range of Motion After the Last Injection	30 days after last treatment to the primary joint
Time to First Achieve and Maintain Clinical Success After the Last Injection	First evaluation visit on which clinical success is achieved and maintained through the Day 30 evaluation of the primary joint
Clinical Success After the First Injection	30 days after first treatment to the primary joint
Percent Reduction From Baseline Contracture After the First Injection	30 days after first treatment to the primary joint
Change From Baseline Range of Motion After the First Injection	30 days after first treatment to the primary joint

Collaborators and Investigators

• Sponsor: Stony Brook University
• Collaborators: Endo Pharmaceuticals; Biospecifics Technologies Corp.
• Investigators: Principal Investigator: Lawrence C Hurst, MD, Stony Brook University

Publications and helpful links

General Publications

• Badalamente MA, Hurst LC, Hentz VR. Collagen as a clinical target: nonoperative treatment of Dupuytren's disease. J Hand Surg Am. 2002 Sep;27(5):788-98. doi: 10.1053/jhsu.2002.35299.

Helpful Links

• XIAFLEX Prescribing Information

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): August 1, 2005
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: November 29, 2005
• First Submitted That Met QC Criteria: November 29, 2005
• First Posted (Estimate): December 1, 2005

Study Record Updates

• Last Update Posted (Estimate): December 9, 2010
• Last Update Submitted That Met QC Criteria: November 5, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Dupuytren's contracture; fixed flexion contracture
• 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: DUPY 303