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

A Phase 3, Open-Label Extension Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Advanced Dupuytren's Disease

Study AUX-CC-858 was an open-label continuation of the double-blind Study AUX-CC-857 (NCT00528606). Subjects who complete the Day 90 visit after their initial injection in Study AUX-CC-857 (NCT00528606) entered into Study AUX-CC-858. Subjects who required further treatment in Study AUX-CC-858, either because their treated metacarpophalangeal and/or proximal interphalangeal (PIP) joints did not have a reduction in contracture to 5° or less, the cord affecting that joint received less than three injections of AA4500, or they had other eligible cords that received no treatment in AUX-CC-857 (NCT00528606), had the option to receive up to five injections of AA4500 in this extension study. Subjects requiring further treatment were followed for efficacy and safety on Days 1, 7, and 30 after each injection, with injections separated by four weeks. Follow-up visits for the determination of efficacy and safety were conducted on Day 90, Month 6, and Month 9.

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.

Study Overview

• Status: Completed
• Conditions: Advanced Dupuytren's Disease
• Intervention / Treatment: Biological: AA4500

• Study Type: Interventional
• Enrollment (Actual): 286
• Phase: Phase 3

Contacts and Locations

Study Locations

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

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 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 naïve to AA4500 treatment or had received only one or two injections of AA4500 for the treatment of advanced Dupuytren's disease in AUX-CC-857 ((NCT00528606).
• Were judged to be in good health.
• Must have participated in protocol AUX-CC-857 (NCT00528606).

Exclusion Criteria:

• Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands.
• Had received treatment for advanced Dupuytren's disease within 90 days of enrollment on the joint selected for the initial injection of AA4500, including surgery (fasciectomy or surgical fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AA4500 0.58 mg	Biological: AA4500; Subjects may have received up to five injections of AA4500 0.58 mg into the cords of the affected hand, with each injection separated by at least 30 days. Individual cords may have received up to a maximum of three AA4500 injections.; Other Names: XIAFLEX®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in Contracture to 5° or Less	Successfully treated or clinical success in non-primary joints defined as reduction in contracture to within 0-5° of normal within 30 days of injection.	Within 30 days after last injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Improvement After the Last Injection	Clinical improvement in non-primary joints defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection	Baseline, within 30 days after last injection
Percent Reduction From Baseline Contracture After the Last Injection	Percent change in degree of contracture in non-primary joints measured as 100 * (baseline contracture - last available post-injection contracture)/baseline contracture.	Baseline, Day 30 after last injection
Change From Baseline Range of Motion After the Last Injection	Change in degree of range of motion in non-primary joints measured as last available post-injection range of motion - baseline range of motion	Baseline, Day 30 after last injection
Time to Reach Clinical Success	Clinical success in non-primary joints defined as reduction in contracture to within 0-5° of normal within 30 days of injection, displayed in post injection time point categories	Within 30 days after last injection
Clinical Success After the First Injection	Clinical success in non-primary joints defined as reduction in contracture to within 0-5° of normal within 30 days of injection.	Within 30 days after first injection
Clinical Improvement After the First Injection	Clinical improvement in non-primary joints defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection	Baseline, within 30 days after first injection
Percent Reduction From Baseline Contracture After the First Injection	Percent change in degree of contracture in non-primary joints measured as 100 * (baseline contracture - last available post-injection contracture)/baseline contracture.	Baseline, Day 30 after first injection
Change From Baseline Range of Motion After the First Injection	Change in degree of range of motion in non-primary joints measured as last available post-injection range of motion - baseline range of motion	Baseline, Day 30 after first injection

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: Veronica Urdaneta, MD, Endo Pharmaceuticals

Publications and helpful links

Helpful Links

• XIAFLEX Prescribing Information

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2007
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: September 11, 2007
• First Submitted That Met QC Criteria: September 11, 2007
• First Posted (Estimate): September 12, 2007

Study Record Updates

• Last Update Posted (Actual): December 2, 2017
• Last Update Submitted That Met QC Criteria: October 26, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• 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: AUX-CC-858