Clinical Study for the Treatment of Adhesive Capsulitis of the Shoulder

Phase 2

Completed

Conditions: Frozen Shoulder
Adhesive Capsulitis

Interventions: Biological: Collagenase Clostridium Histolyticum
Other: Placebo

Registration Number: NCT02006719

Lead Sponsor: Endo Pharmaceuticals

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

Detailed Description: Study is a Phase 2b, double-blind, placebo-controlled study of the safety and efficacy of AA4500 for the treatment of adhesive capsulitis of the shoulder. To be eligible for treatment, a subject must have unilateral idiopathic adhesive capsulitis of the shoulder with restricted range of motion in the affected shoulder for at least 3 months but not more than 12 months. Subjects will be screened for study eligibility within 28 days before injection of study drug.

Approximately 300 adult women and men are to be enrolled in this study. Following screening and determination of study eligibility, subjects will be randomized 3:1 to receive 0.58 mg of AA4500 or placebo. Subjects will receive up to 3 injections of study drug. Each injection will be separated by a minimum of 21 days. Subjects will also be instructed in home shoulder exercises after the first injection.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 322

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Collagenase Clostridium Histolyticum	Collagenase Clostridium Histolyticum	Up to 3 injections of .58 mg/1 mL of collagenase clostridium histolyticum (CCH), minimum of 21 days apart and home shoulder exercise.
Placebo	Placebo	Up to 3 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Day 95 in Active Forward Flexion	Baseline, day 95	Active range of motion (AROM) measurement using a goniometer to assess forward flexion in the affected shoulder

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Day 95 in Adapted American Shoulder and Elbow Surgeons (ASES) Function Subscale	Baseline, day 95	Function subscale score ranging from 0-50, with 0 being most dysfunctional, derived from participant assessment of ability to do 10 activities with affected shoulder/arm where 0=unable to do to, 1=very difficult to do, 2=somewhat difficult, and 3=not difficult, and calculated as (cumulative total score for the 10 activity items) × (5/3); adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation (United States adapted version).
Change From Baseline to Day 95 in Pain With Movement Using 11-point Numeric Rating Scale (NRS)	Baseline, day 95	Participant assessment of pain in response to "How bad is the pain upon movement of your affected shoulder at its worst in the last 24 hours?" using an 11-point NRS where 0=no pain at all and 10=pain as bad as it can be.
Change From Baseline to Day 95 in Active Abduction	Baseline, day 95	AROM measurement using a goniometer to assess abduction in the affected shoulder
Change From Baseline to Day 95 in Passive Forward Flexion	Baseline, day 95	Passive range of motion (PROM) measurement using a goniometer to assess forward flexion in the affected shoulder
Change From Baseline to Day 95 in Passive Abduction	Baseline, day 95	PROM measurement using a goniometer to assess abduction in the affected shoulder
Change From Baseline to Day 95 in Active Internal Rotation	Baseline, day 95	AROM measurement using a goniometer to assess internal rotation in the affected shoulder
Change From Baseline to Day 95 in Active External Rotation	Baseline, day 95	AROM measurement using a goniometer to assess external rotation in the affected shoulder
Change From Baseline to Day 95 in Passive Internal Rotation	Baseline, day 95	PROM measurement using a goniometer to assess internal rotation in the affected shoulder
Change From Baseline to Day 95 in Passive External Rotation	Baseline, day 95	PROM measurement using a goniometer to assess external rotation in the affected shoulder
Change From Baseline to Day 95 in Adapted ASES Pain Subscale	Baseline, day 95	Pain subscale score ranging from 0-50, with 0 being greatest pain, derived from participant overall assessment of pain in response to "How bad is the pain in your affected shoulder today?" using an 11-point NRS where 0=no pain at all and 10=pain as bad as it can be and calculated as (10 - NRS score) x 5; adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation
Subject Satisfaction With Treatment at Day 95	Day 95	Participant assessment of satisfaction with treatment rated as very satisfied, quite satisfied, neither satisfied nor dissatisfied, quite dissatisfied, or very dissatisfied.
Investigator Assessment of Improvement With Treatment at Day 95	Day 95	Investigator assessment of degree of improvement in severity of the participant's treated shoulder compared with screening rated as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.

Trial Locations

Locations (46): Injury Care Medical Center
🇺🇸
Boise, Idaho, United States
Great Falls Clinic
🇺🇸
Great Falls, Montana, United States
Non-Surgical Orthopedics, P.C. / Georgia Institute for Clinical Research, LLC
🇺🇸
Marietta, Georgia, United States
Centex Studies
🇺🇸
Houston, Texas, United States
Nevada Orthopedic & Spine Center
🇺🇸
Las Vegas, Nevada, United States
Temecula Rheumatology & Internal Medicine
🇺🇸
Murrieta, California, United States
Rockford Orthopedic Associates
🇺🇸
Rockford, Illinois, United States
Stony Brook University Medical Center (SUNY)
🇺🇸
Stony Brook, New York, United States
Repatriation Hospital
🇦🇺
VIC, Australia
Hand and Upper Limb Centre
🇦🇺
WA, Australia
Advance Med Clinical Research
🇺🇸
Carlsbad, California, United States
The Neuromusculoskeletal Center of the Cascades d.b.a. The Center
🇺🇸
Bend, Oregon, United States
Danville Orthopedic Clinic, Inc.
🇺🇸
Danville, Virginia, United States
Coastal Clinical Research
🇺🇸
Mobile, Alabama, United States
Wake Research Associates
🇺🇸
Raleigh, North Carolina, United States
PRN of Kansas
🇺🇸
Wichita, Kansas, United States
Clearview Medical Research
🇺🇸
Santa Clarita, California, United States
Florida Research Associates
🇺🇸
DeLand, Florida, United States
Bone and Joint Clinic
🇺🇸
Gretna, Louisiana, United States
Triwest Research Associates
🇺🇸
El Cajon, California, United States
Rockford Orthopedics Associates
🇺🇸
Rockford, Illinois, United States
Sports Medicine Professionals
🇦🇺
Richmond, Victoria, Australia
Shrock Orthopedic Research, LLC
🇺🇸
Fort Lauderdale, Florida, United States
Indiana Hand to Shoulder Center
🇺🇸
Indianapolis, Indiana, United States
Central Kentucky Research Associates
🇺🇸
Lexington, Kentucky, United States
Blair Orthopedic Associates, Inc.
🇺🇸
Altoona, Pennsylvania, United States
Royal Prince Alfred
🇦🇺
NSW, Australia
St George Hospital
🇦🇺
NSW, Australia
Peninsula Private Hospital
🇦🇺
Queensland, Australia
QPharm
🇦🇺
Queensland, Australia
Hunter Clinical Research
🇦🇺
NSW, Australia
Emeritus Research
🇦🇺
VIC, Australia
Epworth Hospital
🇦🇺
VIC, Australia
Alabama Orthopaedic Center-Research
🇺🇸
Birmingham, Alabama, United States
Menzies Research Institute
🇦🇺
Tasmania, Australia
Arthritis and Rheumatism Associates, PC
🇺🇸
Wheaton, Maryland, United States
Arizona Research Center, Inc.
🇺🇸
Phoenix, Arizona, United States
Core Orthopedic Medical Center
🇺🇸
Encinitas, California, United States
Colorado Orthopedic Consultants, PC
🇺🇸
Englewood, Colorado, United States
Clinical Research of West Florida
🇺🇸
Tampa, Florida, United States
Triangle Orthopedic Associates, PA
🇺🇸
Durham, North Carolina, United States
Jewett Orthopedic Clinic
🇺🇸
Orlando, Florida, United States
Commonwealth Orthopaedics & Rehabilitation
🇺🇸
Arlington, Virginia, United States
MedPharmics, LLC
🇺🇸
Metairie, Louisiana, United States
Texas Orthopedic Specialist
🇺🇸
Bedford, Texas, United States
University of Pennsylvania Penn Orthopaedics
🇺🇸
Philadelphia, Pennsylvania, United States