Non-US Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease (CORD-II)

This study has been completed.
Sponsor:
Information provided by:
Auxilium Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00533273
First received: September 20, 2007
Last updated: November 16, 2010
Last verified: November 2010
  Purpose

This 12-month study had two phases: a 90-day double-blind, randomized, placebo-controlled phase and a nine-month open-label extension phase. Before treatment, eligible subjects were stratified by the primary joint type (30 metacarpophalangeal [MP] joints and 30 proximal interphalangeal [PIP] joints) and by severity of the primary joint contracture (ie, up to 50° or >50° for MP joints and up to 40° or >40° for PIP joints) and then randomized in a 2:1 ratio to either AA4500 0.58 mg or placebo. Upon completion of the double-blind phase (ie, 90-day evaluation after the first injection), all subjects were eligible to enter the open-label extension phase of the study in which they were followed for an additional nine months. Subjects who required further treatment because they either did not achieve reduction in contracture to 5° or less, the cord affecting the primary joint received placebo, another cord received less than three injections of AA4500, or they had untreated cords that were affecting other joints had the option to receive up to five additional injections of AA4500 0.58 mg in the open-label extension phase, with individual cords receiving up to three injections of AA4500.

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.


Condition Intervention Phase
Advanced Dupuytren's Disease
Biological: collagenase clostridium histolyticum
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Advanced Dupuytren's Disease Followed by an Open-Label Extension Phase

Resource links provided by NLM:


Further study details as provided by Auxilium Pharmaceuticals:

Primary Outcome Measures:
  • Reduction in Contracture to 5° or Less of the Primary Joint [ Time Frame: Within 30 days after the last injection ] [ Designated as safety issue: No ]

    The Primary Outcome Measure for patients treated with AA4500 is the percentage of 45 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 21 joints that were successfully treated where "successfully treated" was defined as reduction in contracture to 5° or less.



Secondary Outcome Measures:
  • Clinical Improvement After the Last Injection [ Time Frame: 30 days after last treatment to the primary joint ] [ Designated as safety issue: No ]
  • Percent Reduction From Baseline Contracture After the Last Injection [ Time Frame: 30 days after last treatment to the primary joint ] [ Designated as safety issue: No ]
  • Change From Baseline Range of Motion After the Last Injection [ Time Frame: 30 days after last treatment to the primary joint ] [ Designated as safety issue: No ]
  • Time to First Achieve and Maintain Clinical Success After the Last Injection [ Time Frame: First evaluation visit on which clinical success is achieved and maintained through the Day 30 evaluation of the primary joint ] [ Designated as safety issue: No ]
  • Clinical Success After the First Injection [ Time Frame: 30 days after first treatment to the primary joint ] [ Designated as safety issue: No ]
  • Clinical Improvement After the First Injection [ Time Frame: 30 days after first treatment to the primary joint ] [ Designated as safety issue: No ]
  • Percent Reduction From Baseline Contracture After the First Injection [ Time Frame: 30 days after first treatment to the primary joint ] [ Designated as safety issue: No ]
  • Change From Baseline Range of Motion After the First Injection [ Time Frame: 30 days after first treatment to the primary joint ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: August 2007
Study Completion Date: January 2009
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AA4500 0.58 mg Biological: collagenase clostridium histolyticum
Subjects could have received up to three injections of AA4500 0.58 mg/placebo into the cord of the affected hand in the double-blind phase. In the open-label extension phase, subjects could have received up to five additional injections of AA4500, with each injection separated by at least 30 days. Individual joints could have received up to a maximum of three AA4500 injections.
Other Names:
  • XIAFLEX®
  • AA4500
Placebo Comparator: Placebo Biological: collagenase clostridium histolyticum
Subjects could have received up to three injections of AA4500 0.58 mg/placebo into the cord of the affected hand in the double-blind phase. In the open-label extension phase, subjects could have received up to five additional injections of AA4500, with each injection separated by at least 30 days. Individual joints could have received up to a maximum of three AA4500 injections.
Other Names:
  • XIAFLEX®
  • AA4500

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 naive to AA4500 treatment
  • Were judged to be in good health, based upon the results of a medical history, physical examination, and safety laboratory profile.

Exclusion Criteria:

  • Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands.
  • Had received a treatment for advanced Dupuytren's disease, including surgery (fasciectomy or surgical fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon on the selected primary joint within 90 days before the first dose of study drug.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00533273

Locations
Australia, Queensland
Rivercity Research
Auchenflower, Queensland, Australia, 4067
Brisbane Hand & Upper Limb Clinic
Brisbane, Queensland, Australia, 4000
Caboolture Clinical Research Centre
Caboolture, Queensland, Australia, 4510
Peninsula Clinical Research Centre
Kippa Ring, Queensland, Australia, 4019
Australia, Tasmania
Menzies Reserarch Institute
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Emeritus Research
Malvern, Victoria, Australia, 3144
Australia, Western Australia
Royal Perth Hospital
Shenton Park, Western Australia, Australia, 6007
Sponsors and Collaborators
Auxilium Pharmaceuticals
Investigators
Study Director: John Rodzvilla, MD Auxilium Pharmaceuticals, Inc
  More Information

Additional Information:
No publications provided

Responsible Party: John Rodzvilla/ Vice President, Medical Development, Auxilium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00533273     History of Changes
Other Study ID Numbers: AUX CC 859
Study First Received: September 20, 2007
Results First Received: September 24, 2010
Last Updated: November 16, 2010
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration

Additional relevant MeSH terms:
Dupuytren Contracture
Connective Tissue Diseases
Contracture
Muscular Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on October 20, 2014