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

Study Overview
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Brief Summary
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This was a Phase 3, 9-month, open-label study conducted in the United States. Subjects with a diagnosis of advanced Dupuytren's disease 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 evaluation and injection were enrolled. 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.

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

Conditions
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Advanced Dupuytren's Disease

Intervention / Treatment
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* Biological: collagenase clostridium histolyticum


Participation Criteria
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Eligibility Criteria
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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 one or two injections of AA4500 for the treatment of advanced Dupuytren's disease in Auxilium Studies AUX-CC-851, AUX-CC-853, or AUX-CC-855. Were judged to be in good health. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AA4500 0.58 mg<br> | Biological: collagenase clostridium histolyticum<br>* Up to five injections of AA4500 into cord(s) of the affected hand(s). Each injection was separated by at least 30 days.<br>* Other names: AA4500;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Contracture to 5° or Less | The Primary Outcome Measure is the percentage of joints that were successfully treated where successfully treated was defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection | Within 30 days after the last injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Improvement After the Last Injection | Clinical Improvement is defined as >=50% percent reduction from baseline in 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 measured as 100*(baseline contracture -last available post-injection contracture)/baseline contracture) | Baseline, within 30 days after last injection | 
| Change From Baseline Range of Motion After the Last Injection | Change in degree of range of motion measured as last available post-injection range of motion - baseline range of motion. | Baseline, 30 days after last injection | 
| Time to Reach Clinical Success | Clinical success is defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection, displayed in post-injection timepoint categories. | First evaluation visit on which clinical success is achieved through the Day 30 evaluation | 
| Clinical Success After the First Injection | Clinical Success is defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection. | Within 30 days after first injection | 
| Clinical Improvement After the First Injection | Clinical Improvement is defined as >=50% reduction from baseline in the degree of contracture within 30 days after the first injection | Baseline; within 30 days after first injection | 
| Percent Reduction From Baseline Contracture After the First Injection | Percent change in degree of contracture is measured as 100* (baseline contracture- last available post-injection contracture)/baseline contracture. | Baseline; within 30 days after first injection | 
| Change From Baseline Range of Motion After the First Injection | Change in degree of range of motion measured as last available post-injection range of motion-baseline range of motion. | Baseline; within 30 days after first injection |