A Pharmacokinetic Study of AA4500 (XIAFLEX™, Proposed Name) in Subjects With Dupuytren's Contracture

Study Overview
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Brief Summary
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A Phase 1, open-label, single-dose pharmacokinetic study in subjects with Dupuytren's contracture conducted at one site in the United States. All subjects received a single dose of AA4500 0.58 mg, which was injected directly into the cord affecting either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint. Pharmacokinetic blood samples were collected before dosing, at predetermined time points through the 24 hours after dosing, Day 7, and Day 30. Efficacy and safety assessments were performed up to 30 days after the AA4500 0.58 injection. 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 1, Open-Label Study to Assess the Pharmacokinetics and Safety of a Single Injection of AA4500 0.58 mg in Subjects With Dupuytren's Contracture

Conditions
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Dupuytren's Contracture

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 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. 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 naive to AA4500 treatment. 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 Dupuytren's contracture within 90 days of the AA4500 injection to the MP or PIP selected, 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: Other
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>* Single dose of AA4500 0.58 mg into the cord<br>* Other names: AA4500;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With AUX I and AUX II Detected in Their Blood After a Single Dose of AA4500 | AUX I and AUX II are the constituent protein collagenases of collagenase clostridium histolyticum (AA4500). Plasma concentrations of AUX I and AUX II were assessed through an enzymye-linked-immunoabsorbent assay (ELISA). | Before dosing, at predetermined time points through the 24 hours after dosing, Day 7, and Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Success | Clinical success defined as a reduction in contracture (ie, flexion deformity) to ≤5° of normal as measured by finger goniometry 30 days after an injection. Last observation carried forward (LOCF) after the injection was used if the status at day 30 could not be determined. | 30 days after treatment to the primary joint | 
| Clinical Improvement | Clinical improvement defined as ≥50% reduction from baseline in contracture within 30 days of the injection. LOCF after the injection was used if the status at day 30 could not be determined. | 30 days after treatment to the primary joint | 
| Percent Change From Baseline Contracture | Change from baseline in the degree of fixed-flexion contracture calculated as 100 times (baseline contracture minus last available post-injection contracture measurement) divided by baseline contracture where a positive change indicates a reduction in the degree of contracture. | Baseline, 30 days after treatment to the primary joint | 
| Change From Baseline Range of Motion | Range of motion defined as the difference between the finger extension angle and finger flexion angle expressed in degrees | Baseline, 30 days after treatment to the primary joint | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Assessment of AUX I and/or AUX II in human plasma