Administration of Two Injections for Multiple Dupuytren's Contractures

Study Overview
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Brief Summary
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The objectives of this study are to assess the safety and efficacy of concurrent administration of two injections of AA4500 into the same hand of subjects with multiple Dupuytren's contractures caused by palpable cords.

Detailed Description
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Methodology/Study Design: This is an open-label, study in men and women with multiple Dupuytren's contractures. Approximately 60 subjects who have at least two Dupuytren's contractures caused by palpable cords in the same hand will be enrolled. After all pre-injection procedures are completed on Day 1, eligible men and women will receive two concurrent injections of AA4500 0.58 mg into the same hand. On Day 2, a finger extension procedure to facilitate cord disruption will be performed in those subjects who do not have spontaneous disruption of their cord(s). Follow-up visits for the evaluation of safety and efficacy will be on Day 8, Day 30, and Day 60. Upon completion of the Day 60 follow-up visit, subjects who require further treatment will have the option to receive three additional open-label treatments according to the XIAFLEX package insert (Appendix C). Subjects may receive up to a total of five injections and individual cords may receive up to a total of three injections.

Official Title
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An Open-label Study to Assess the Safety and Efficacy of Concurrent Administration of Two Injections of AA4500 0.58 mg Into the Same Hand of Subjects With Multiple Dupuytren's Contractures

Conditions
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Dupuytren's Contracture

Intervention / Treatment
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* Biological: AA4500 collagenase clostridium histolyticum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent Be a man or woman ≥ 18 years of age Have a diagnosis of Dupuytren's disease and have at least 2 fixed-flexion contractures on the same hand that are ≥ 20º in PIP and/or MP joints in fingers, other than the thumbs, which are caused by palpable cords suitable for treatment Have a positive table top test defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top Either be using an accepted method of birth control (ie, surgical sterilization; intra uterine contraceptive device; oral contraceptive; diaphragm or condom in combination with contraceptive cream, or jelly or foam) and have negative pregnancy testing before administration of AA4500, if a female of childbearing potential, or be a postmenopausal female (no menses for at least 1 year or hysterectomy) Not have any clinically significant medical history or condition(s) that would, in the opinion of the investigator, substantially increase the risk associated with the subject's participation in the protocol or compromise the scientific objectives of the study Be able to comply with the study visit schedule as specified in the protocol Exclusion Criteria: Received surgery (fasciectomy or surgical fasciotomy) and/or needle aponeurotomy/fasciotomy on the selected joints to be treated within 90 days before the first injection of AA4500 Has a chronic muscular, neurological, or neuromuscular disorder that affects the hands Has a known systemic allergy to collagenase or any other excipient of AA4500 Has received any collagenase treatments (eg, Santyl® ointment and/or XIAFLEX/XIAPEX) within 30 days before injection of AA4500 Is currently receiving or plans to receive anticoagulant medication or has received anticoagulant medication (except for ≤ 150 mg aspirin daily and over-the-counter nonsteroidal anti-inflammatory drugs [NSAIDs]) within 7 days before injection of AA4500) Has a known recent history of stroke, bleeding, or other medical condition, which in the investigator's opinion would make the subject unsuitable for enrollment in the study Is known to be immunocompromised or human immunodeficiency virus (HIV) positive Has a history of illicit drug abuse or alcoholism within the year before injection of AA4500 Received an investigational drug within 30 days before injection of AA4500 Is a pregnant or lactating female Has any clinically significant medical history or condition(s), including conditions that affect the hands, that would, in the opinion of the investigator, substantially increase the risk associated with the subject's participation in the protocol or compromise the scientific objectives of the study Has jewelry on the hand to be treated that cannot be removed

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<br>AA4500 collagenase clostridium histolyticum | Biological: AA4500 collagenase clostridium histolyticum<br>* 2 concurrent injections (0.58 mg) into 2 cords on the same hand<br>* Other names: Xiapex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Total Fixed Flexion | Total fixed flexion is defined as the sum of the fixed flexion contractures of the two joints receiving treatment. Change in fixed-flexion contracture is measured in degrees where a decrease of 100% would correspond to a reduction in contracture to 0 degrees | 30 days after last injection | 
| Change in Total Range of Motion | The total range of motion is the sum of the range of motion measurements of the two treated joints. Range of motion is defined as difference between full flexion angle and full extension angle expressed in degrees. | 30 days after last injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Satisfaction With Treatment | At the Day 60 follow-up visit, each subject will be asked to rate his/her satisfaction with treatment as follows: Very Satisfied Quite Satisfied Neither Satisfied nor Dissatisfied Quite Dissatisfied Very Dissatisfied | 60 days after last injection | 
| Investigator Assessment of Improvement With Treatment | At the Day 60 follow-up visit, the investigator will determine the degree of improvement in the severity of the subject's treated finger(s) compared with screening as follows: Very Much Improved Much improved Minimally Improved No Change Minimally Worse Much Worse Very Much Worse | 60 days after last injection | 
| Clinical Success by Joint Type | Clinical success is defined as a reduction in fixed flexion contracture to 5° or less 30 days after injection of AA4500. | 30 days after injection |