Non-US Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease
Condition: Advanced Dupuytren's Disease
MeSH terms: Dupuytren Contracture
Intervention: collagenase clostridium histolyticum
Intervention description: Subjects could have received up to three injections of AA4500 0.58 mg/placebo into the cord of the affected hand in the double-blind phase. In the open-label extension phase, subjects could have received up to five additional injections of AA4500, with each injection separated by at least 30 days. Individual joints could have received up to a maximum of three AA4500 injections.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This 12-month study had two phases: a 90-day double-blind, randomized, placebo-controlled
      phase and a nine-month open-label extension phase. Before treatment, eligible subjects were
      stratified by the primary joint type (30 metacarpophalangeal [MP] joints and 30 proximal
      interphalangeal [PIP] joints) and by severity of the primary joint contracture (ie, up to 50°
      or >50° for MP joints and up to 40° or >40° for PIP joints) and then randomized in a 2:1
      ratio to either AA4500 0.58 mg or placebo. Upon completion of the double-blind phase (ie,
      90-day evaluation after the first injection), all subjects were eligible to enter the
      open-label extension phase of the study in which they were followed for an additional nine
      months. Subjects who required further treatment because they either did not achieve reduction
      in contracture to 5° or less, the cord affecting the primary joint received placebo, another
      cord received less than three injections of AA4500, or they had untreated cords that were
      affecting other joints had the option to receive up to five additional injections of AA4500
      0.58 mg in the open-label extension phase, with individual cords receiving up to three
      injections of AA4500.

      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.
    

Eligibility criteria:

        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 naive to AA4500 treatment

          -  Were judged to be in good health, based upon the results of a medical history,
             physical examination, and safety laboratory profile.

        Exclusion Criteria:

          -  Had a chronic muscular, neurological, or neuromuscular disorder that affected the
             hands.

          -  Had received a treatment for advanced Dupuytren's disease, 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.