Clinical Study for the Treatment of Adhesive Capsulitis of the Shoulder
Condition: Adhesive Capsulitis; Frozen Shoulder
MeSH terms: Bursitis
Intervention: Collagenase Clostridium Histolyticum; Placebo
Intervention description: Treatment of Adhesive Capsulitis; Placebo injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 322.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Adhesive Capsulitis; Frozen Shoulder; Shoulder Range of Motion limitation; Shoulder Pain

Summary:

      The objectives of this study are to assess the safety, effectiveness, and immunogenicity of
      AA4500 in the treatment of adhesive capsulitis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Unilateral idiopathic adhesive capsulitis of one shoulder for at least 3 months but
             not more than 12 months (Frozen Stage)

          -  Normal range of motion in the contralateral shoulder

          -  Restricted active range of motion (AROM) in the affected shoulder defined as: a
             deficit of at least 60 degrees in total AROM in the affected shoulder as compared with
             the total AROM in the contralateral shoulder and a deficit of at least 30 degrees in
             AROM in at least one of the following planes as compared with the contralateral
             shoulder:

               -  Forward flexion

               -  Abduction

               -  External rotation with the elbow up to 90 degrees abduction

               -  Internal rotation with the elbow up to 90 degrees abduction

        Exclusion Criteria:

          -  Has received treatment for adhesive capsulitis or is planning to receive treatment for
             adhesive capsulitis at any time during the study including but not limited to:

               -  physical therapy or acupuncture within 2 weeks before the first injection of
                  study drug

               -  intra-articular or intrabursal injection(s) of lidocaine; suprascapular nerve
                  blocks; corticosteroids, electroanalgesic and/or thermoanalgesic modalities
                  within 1 month before the screening visit

               -  intra-articular or intrabursal injection(s) of sodium hyaluronate and/or
                  glenohumeral distension arthrography within 3 months before the screening visit

               -  surgical intervention (including shoulder manipulation under anesthesia) at any
                  time

          -  Has any of the following conditions, as determined by investigator to be potentially
             confounding to the evaluation of safety and efficacy:

               -  Adhesive capsulitis as a result of traumatic injury (ie, direct injury to the
                  shoulder such as fracture of the humerus or clavicle immediately preceding the
                  onset of this episode of adhesive capsulitis). Traumatic events in the past that
                  are not temporally related to the onset of this episode of adhesive capsulitis
                  would not necessarily exclude a subject from participating in the study.

               -  Active subacromial impingement in the affected shoulder

               -  Calcified tendonitis in the affected shoulder

               -  Glenohumeral joint arthritis in the affected shoulder

               -  Arthrosis of the affected shoulder

               -  Chondrolysis of the affected shoulder

               -  Subscapularis tendon rupture of the affected shoulder

               -  Other rotator cuff injuries of the affected shoulder

               -  Uncontrolled hypertension

               -  Uncontrolled diabetes

               -  Uncontrolled thyroid disease

               -  History of thrombosis or post-thrombosis syndrome

               -  Physical impairment that would preclude performing the protocol defined exercises

               -  Active infection in area to be treated

               -  Clinically significant neurological disease

               -  Bleeding disorder

               -  Chronic use of anticoagulation medications and the subject cannot be cleared
                  medically to stop taking medication for 7 days prior to each injection. Less than
                  or equal to 150 mg aspirin is allowed during the study.

               -  Known active hepatitis A, B, or C

               -  Other significant medical condition (eg, morbid obesity, cervical disc disease),
                  which in the investigator's opinion would make the subject unsuitable for
                  enrollment in the study

          -  Has received oral or intravenous steroids for any reason within 3 weeks before the
             screening visit

          -  Has received an investigational drug or treatment within 30 days before the first dose
             of study drug.

          -  Has a known allergy to collagenase or any other excipient of AA4500 or any other
             procedural medication.

          -  Has, at any time, received collagenase for the treatment of adhesive capsulitis.

          -  Is unable to undergo an x-ray or MRI (contraindication) evaluation of the affected
             shoulder.

          -  Is planning to be treated with commercial XIAFLEX at any time during the study.