AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Dupuytren's Contracture - Full Text View

Sponsor:	Auxilium Pharmaceuticals
Information provided by:	Auxilium Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00528606

Purpose

This was a Phase 3, double-blind, randomized, placebo-controlled study conducted in the United States. Subjects with a diagnosis of Dupuytren's contracture 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 injection were randomized 2:1 to receive AA4500 0.58 mg or placebo.

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
Dupuytren's Contracture	Biological: collagenase clostridium histolyticum Biological: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) 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 Dupuytren's Contracture

Resource links provided by NLM:

Drug Information available for: Collagenase

U.S. FDA Resources

Further study details as provided by Auxilium Pharmaceuticals:

Primary Outcome Measures:

Clinical Success (Reduction in Contracture to 5° or Less) of the Primary Joint After the Last Injection [ 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 203 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 103 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:	308
Study Start Date:	August 2007
Study Completion Date:	October 2008
Primary Completion Date:	April 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/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
Placebo Comparator: Placebo	Biological: Placebo Subjects could have received up to three injections of 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.

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 Dupuytren's contracture, 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 that had never been treated with AA4500.
Had a positive "table top test," defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top.
Judged to be in good health.

Exclusion Criteria:

Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands.
Had received a treatment for Dupuytren's contracture, 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00528606

Locations

United States, California
100 UCLA Medical Plaza, Suite 305
Los Angeles, California, United States, 90095
Hand Surgery Clinic
Palo Alto, California, United States, 94304
United States, Colorado
Hand Surgery Associates, PC
Denver, Colorado, United States, 80210
United States, Georgia
The Hand and Upper Extremity Center of Georgia, P.C.
Atlanta, Georgia, United States, 30342
United States, Illinois
Rockford Orthopedic Associates, Ltd.
Rockford, Illinois, United States, 61107
United States, Indiana
The Indiana Hand Center
Indianapolis, Indiana, United States, 46260
United States, Massachusetts
Brigham and Women's Hospital, Department of Orthopedic Surgery
Boston, Massachusetts, United States, 02115
Newton-Wellesley Hospital
Newton, Massachusetts, United States, 02462
United States, Minnesota
TRIA Orthopaedic Center
Minneapolis, Minnesota, United States, 55431
United States, New York
Hospital for Special Surgery
New York, New York, United States, 10021
SUNY Stony Brook - Department of Orthopedics
Stony Brook, New York, United States, 11794
United States, Oklahoma
Health Research Institute
Oklahoma city, Oklahoma, United States, 73109
United States, Pennsylvania
Hand Microsurgery & Reconstructive Orthopaedics
Erie, Pennsylvania, United States, 16550
University Orthopedics Center
State College, Pennsylvania, United States, 16801
United States, Rhode Island
Department of Orthopaedics, Brown University, Rhode Island Hospital
Providence, Rhode Island, United States, 02905

Sponsors and Collaborators

Auxilium Pharmaceuticals

Investigators

Study Director:

John Rodzvilla, MD

Auxilium Pharmaceuticals, Inc

More Information

Additional Information:

XIAFLEX Medication Guide This link exits the ClinicalTrials.gov site

XIAFLEX Prescribing Information This link exits the ClinicalTrials.gov site

No publications provided by Auxilium Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Witthaut J, Bushmakin AG, Gerber RA, Cappelleri JC, Le Graverand-Gastineau MP. Determining clinically important changes in range of motion in patients with Dupuytren's Contracture: secondary analysis of the randomized, double-blind, placebo-controlled CORD I study. Clin Drug Investig. 2011 Nov 1;31(11):791-8.

Hurst LC, Badalamente MA, Hentz VR, Hotchkiss RN, Kaplan FT, Meals RA, Smith TM, Rodzvilla J; CORD I Study Group. Injectable collagenase clostridium histolyticum for Dupuytren's contracture. N Engl J Med. 2009 Sep 3;361(10):968-79.

Responsible Party:	John Rodzvilla/ Vice President, Medical Development, Auxilium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00528606 History of Changes
Other Study ID Numbers:	AUX-CC-857
Study First Received:	September 11, 2007
Results First Received:	September 24, 2010
Last Updated:	January 18, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Contracture
Dupuytren Contracture
Joint Diseases

Musculoskeletal Diseases
Muscular Diseases
Connective Tissue Diseases

ClinicalTrials.gov processed this record on February 09, 2012