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

NCT00533273 | Completed Phase 3 Results

• 1 other identifier: AUX CC 859
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Advanced Dupuytren's Disease

Outcome Measures

Primary Outcomes (1)

• Reduction in Primary Joint Contracture to 5° or Less

  Successfully treated or clinical success in primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.

  Within 30 days after last injection

Secondary Outcomes (17)

• Clinical Improvement in Primary Joint After the Last Injection

  Baseline, Within 30 days after last injection

• Percent Reduction From Baseline Contracture of Primary Joint After the Last Injection

  Baseline, Day 30 after last injection

• Change From Baseline Range of Motion in Primary Joint After the Last Injection

  Baseline, Day 30 after last injection

• Time to Reach Clinical Success in Primary Joint

  Within 30 days after last injection

• Clinical Success in Primary Joint 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: collagenase clostridium histolyticum

Interventions

collagenase clostridium histolyticum BIOLOGICAL

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.

Also known as: XIAFLEX®, AA4500

AA4500 0.58 mg; 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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Endo Pharmaceuticals: lead

Study Sites (7)

Rivercity Research

Auchenflower, Queensland, 4067, Australia

Location

Brisbane Hand & Upper Limb Clinic

Brisbane, Queensland, 4000, Australia

Location

Caboolture Clinical Research Centre

Caboolture, Queensland, 4510, Australia

Location

Peninsula Clinical Research Centre

Kippa-Ring, Queensland, 4019, Australia

Location

Menzies Reserarch Institute

Hobart, Tasmania, 7000, Australia

Location

Emeritus Research

Malvern, Victoria, 3144, Australia

Location

Royal Perth Hospital

Shenton Park, Western Australia, 6007, Australia

Location

Related Links

• XIAFLEX Prescribing Information

MeSH Terms

Interventions

Microbial Collagenase

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2007
• First Posted: September 21, 2007
• Study Start: August 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: December 2, 2017
• Results First Posted: October 22, 2010

Record last verified: 2017-10

Locations

AU (7)