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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Open-Label Extension 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: AA4500


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 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.

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: AA4500<br>* 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.<br>* Other names: XIAFLEX®;|

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 | 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 |