AA4500 for the Treatment of Adhesive Capsulitis of the Shoulder
Condition: Adhesive Capsulitis; Frozen Shoulder
MeSH terms: Bursitis
Intervention: AA4500 0.29 mg/1 mL; AA4500 0.58 mg/2 mL; AA4500 0.58 mg/1 mL; AA4500 0.58 mg/0.5 mL; Shoulder exercises
Intervention description: treatment of adhesive capsulitis; treatment of adhesive capsulitis; treatment of adhesive capsulitis; treatment of adhesive capsulitis; Home shoulder exercises, minimum of 3 times per day
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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:

          1. Be a male or female and be greater than or equal to 18 years of age

          2. If a female of childbearing potential, have a negative urine pregnancy test and be
             using an effective contraception method (ie, abstinence, intrauterine device (IUD),
             hormonal (estrogen/progestin) contraceptives, or barrier control) for at least one
             menstrual cycle prior to study enrollment and for one menstrual cycle following end of
             study, or be surgically sterile

          3. Have unilateral idiopathic adhesive capsulitis of one shoulder for at least 3 months
             but not more than 12 months before the screening visit and be in Stage 2 (frozen or
             adhesive stage), as determined by the investigator

          4. Have normal range of motion in the contralateral shoulder, as determined by the
             investigator

          5. Have 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

          6. Voluntarily sign and date an informed consent agreement approved by the Institutional
             Review Board/Independent Ethics Committee (IRB/IEC). The subject must also sign an
             authorization form to allow disclosure of his protected health information (PHI). The
             PHI authorization form and informed consent form may be an integrated form or may be
             separate forms depending on the institution.

          7. Be able to complete and understand the various rating instruments in English.

        Exclusion Criteria:

          1. Is a pregnant or lactating female or female intending to become pregnant during the
             study

          2. Is a male who intends to father a child during the study

          3. 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
                  AA4500

               -  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 within 3 months
                  before the screening visit

               -  glenohumeral distension arthrography and/or surgical intervention (including
                  shoulder manipulation under anesthesia) at any time

          4. Has any of the following conditions, as determined by the investigator:

               -  Adhesive capsulitis as a result of traumatic injury

               -  Pain in the affected shoulder at rest that is greater than or equal to 4 on the
                  11-point pain scale

               -  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

               -  Coagulation disorder, using anticoagulant (except for less than or equal to 150
                  mg aspirin) within 7 days prior to each injection day

               -  Known active hepatitis B or C (history of hepatitis A permitted)

               -  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

          5. Is unwilling or unable to cooperate with the requirements of the study including
             completion of all scheduled study visits.

          6. Has received oral or intravenous steroids for any reason within 3 weeks before the
             screening visit

          7. Has received an investigational drug or treatment within 30 days before the first dose
             of study drug.

          8. Has a known systemic allergy to collagenase or any other excipient of AA4500 or any
             other procedural medication.

          9. Has, at any time, received collagenase for the treatment of adhesive capsulitis.

         10. Is unable to undergo an x-ray or MRI (contraindication) evaluation of the affected
             shoulder.

         11. Is planning to be treated with commercial Xiaflex at any time during the study.