Safety and Efficacy of Two Concurrent Injections of AA4500 in Adult Subjects With Multiple Dupuytren's Contractures
Condition: Dupuytren's Contracture
MeSH terms: Dupuytren Contracture; Contracture
Intervention: XIAFLEX / XIAPEX
Intervention description: injection (0.58 mg after reconstitution with sterile diluent [0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride])
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 715.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: XIAFLEX; XIAPEX; Dupuytren's disease; contracture

Summary:

      The primary objective of this study is to assess the safety of two concurrent injections of
      AA4500 into the same hand in subjects with multiple Dupuytren's contractures with palpable
      cords followed 24 to 72 hours later by a finger extension procedure and compare the rate of
      occurrence of targeted serious adverse events (tendon rupture/ligament injury and
      anaphylaxis) to historical rates of the same in clinical studies and post-marketing
      commercial use.

      The secondary objective is to evaluate the efficacy of two concurrent injections of AA4500.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provide a signed and dated informed consent

          2. Be a man or woman ≥ 18 years of age

          3. 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 cord(s) suitable for treatment

          4. Have a positive "table top test" defined as the inability to simultaneously place the
             affected finger(s) and palm flat against a table top

          5. Have a negative urine pregnancy test at screening and before injection of study drug
             and be using a highly effective (ie, < 1% failure rate) contraception method as judged
             by the investigator (eg, abstinence, intrauterine device [IUD], hormonal
             [estrogen/progestin] contraceptives, or barrier control) for at least one menstrual
             cycle prior to study enrollment and for the duration of the study or be surgically
             sterile (if female of childbearing potential); or be a postmenopausal female (no
             menses for at least 1 year or hysterectomy).

          6. Be able to comply with the study visit schedule as specified in the protocol

        Exclusion Criteria:

        A subject will be excluded from study participation if he/she:

          1. Received surgery (fasciectomy or surgical fasciotomy) and/or needle
             aponeurotomy/fasciotomy on the selected joints to be treated within 6 months before
             administration of study drug

          2. Has a chronic muscular, neurological, or neuromuscular disorder that affects the hands

          3. Has a known systemic allergy to collagenase or any other excipient of AA4500

          4. Has received any collagenase treatments (eg, Santyl® ointment and/or XIAFLEX®/XIAPEX®)
             within 30 days before injection of study drug in the hand selected for treatment

          5. Is currently receiving or plans to receive anticoagulant medication or has received
             anticoagulant medication (except for ≤ 150 mg aspirin daily) within 7 days before
             injection of study drug

          6. 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

          7. Received an investigational drug within 30 days before injection of study drug

          8. Is pregnant or intends on becoming pregnant during the study or is breastfeeding a
             child

          9. 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

         10. Has jewelry on the hand to be treated that cannot be removed