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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Dupuytren's Contracture

Intervention / Treatment
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* Biological: collagenase clostridium histolyticum
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AA4500 0.58 mg<br> | Biological: collagenase clostridium histolyticum<br>* 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.<br>* Other names: AA4500;|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Improvement After the Last Injection | Clinical Improvement is defined as >= 50% reduction from baseline in degree of contracture within 30 days of the injection. | Baseline; within 30 days after the 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 the last injection | 
| Change From Baseline Range of Motion After the Last Injection | Change in degree of motion measured as last available post-injection range of motion - baseline range of motion. | 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 | 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 contracture within 30 days of the first injectionor greater of baseline contracture within 30 days of the injection. | Baseline; within 30 days after the first injection | 
| Percent Reduction From Baseline Contracture After the First Injection | Percent change in degree of contracture measured as 100* (baseline contracture - last available post-injection contracture)/baseline contracture. | Baseline, within 30 days after the first injection | 
| Change From Baseline Range of Motion After the First Injection | Change in degree of motion measured as last available post-injection range of motion - baseline range of motion. | Baseline; within 30 days after the first injection |