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

NCT00528606 | Completed Phase 3 Results

• 1 other identifier: AUX-CC-857
• Study Type: interventional
• Target: 308
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Dupuytren's Contracture

Outcome Measures

Primary Outcomes (1)

• Clinical Success (Reduction in Contracture to 5° or Less) of the Primary Joint After the Last Injection

  The Primary Outcome Measure for patients treated with AA4500 is the percentage of joints that were successfully treated where "successfully treated" was defined as reduction in contracture to within 0-5° of normal within 30 days of injection. The Primary Outcome Measure for placebo treated patients is the percentage of joints that were successfully treated where "successfully treated" was defined as reduction in contracture to within 0-5° of normal within 30 days of injection.

  Within 30 days after the last injection

Secondary Outcomes (8)

• Clinical Improvement After the Last Injection

  Baseline; within 30 days after the last injection

• Percent Reduction From Baseline Contracture After the Last Injection

  Baseline; within 30 days after the last injection

• Change From Baseline Range of Motion After the Last Injection

  Baselin; within 30 days after the last injection

• Time to First Achieve Success After the Last Injection

  Last evaluation visit on which clinical success is achieved through the Day 30 evaluation

• Clinical Success (Reduction in Contracture to 5° or Less) After the First Injection

  Within 30 days after first injection

Study Arms (2)

AA4500 0.58 mg

EXPERIMENTAL

Biological: collagenase clostridium histolyticum

Placebo

PLACEBO COMPARATOR

Biological: Placebo

Interventions

collagenase clostridium histolyticum BIOLOGICAL

Subjects could have received up to three injections of AA4500 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.

Also known as: XIAFLEX®, AA4500

AA4500 0.58 mg

Placebo BIOLOGICAL

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Endo Pharmaceuticals: lead

Study Sites (15)

100 UCLA Medical Plaza, Suite 305

Los Angeles, California, 90095, United States

Location

Hand Surgery Clinic

Palo Alto, California, 94304, United States

Location

Hand Surgery Associates, PC

Denver, Colorado, 80210, United States

Location

The Hand and Upper Extremity Center of Georgia, P.C.

Atlanta, Georgia, 30342, United States

Location

Rockford Orthopedic Associates, Ltd.

Rockford, Illinois, 61107, United States

Location

The Indiana Hand Center

Indianapolis, Indiana, 46260, United States

Location

Brigham and Women's Hospital, Department of Orthopedic Surgery

Boston, Massachusetts, 02115, United States

Location

Newton-Wellesley Hospital

Newton, Massachusetts, 02462, United States

Location

TRIA Orthopaedic Center

Minneapolis, Minnesota, 55431, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

SUNY Stony Brook - Department of Orthopedics

Stony Brook, New York, 11794, United States

Location

Health Research Institute

Oklahoma City, Oklahoma, 73109, United States

Location

Hand Microsurgery & Reconstructive Orthopaedics

Erie, Pennsylvania, 16550, United States

Location

University Orthopedics Center

State College, Pennsylvania, 16801, United States

Location

Department of Orthopaedics, Brown University, Rhode Island Hospital

Providence, Rhode Island, 02905, United States

Location

Related Publications (2)

• 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. doi: 10.1007/BF03256918.

  PMID: 21967070 DERIVED

• 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. doi: 10.1056/NEJMoa0810866.

  PMID: 19726771 DERIVED

Related Links

• XIAFLEX Prescribing Information

MeSH Terms

Conditions

Dupuytren Contracture

Interventions

Microbial Collagenase

Condition Hierarchy (Ancestors)

Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Contracture; Muscular Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Collagenases; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases

Results Point of Contact

• Title: Clinical Trial Coordinator
• Organization: Endo Pharmaceuticals, Inc.

clinicalsite.inquiries@endo.com

Study Officials

• Veronica Urdaneta, MD

  Endo Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2007
• First Posted: September 12, 2007
• Study Start: August 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: December 2, 2017
• Results First Posted: October 22, 2010

Record last verified: 2017-10

Locations

US (15)