Clinical Study for the Treatment of Adhesive Capsulitis of the Shoulder

Adhesive Capsulitis Clinical Trial

— AC  

Official title:

A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of AA4500 for the Treatment of Adhesive Capsulitis of the Shoulder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02006719
• Other study ID #: AUX-CC-871
• Status: Completed
• Phase: Phase 2
• First received: December 2, 2013
• Last updated: September 7, 2017
• Start date: November 2013
• Est. completion date: December 2014

Study information

• Verified date: September 2017
• Source: Endo Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 322
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adhesive Capsulitis
• Bursitis
• Frozen Shoulder
• Periarthritis
• Rheumatic Diseases

Intervention

Biological:
• Collagenase Clostridium Histolyticum
Treatment of Adhesive Capsulitis

Other:
• Placebo
Placebo injection

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Endo Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Day 95 in Active Forward Flexion	Active range of motion (AROM) measurement using a goniometer to assess forward flexion in the affected shoulder	Baseline, day 95
Secondary	Change From Baseline to Day 95 in Adapted American Shoulder and Elbow Surgeons (ASES) Function Subscale	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).	Baseline, day 95
Secondary	Change From Baseline to Day 95 in Pain With Movement Using 11-point Numeric Rating Scale (NRS)	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.	Baseline, day 95
Secondary	Change From Baseline to Day 95 in Active Abduction	AROM measurement using a goniometer to assess abduction in the affected shoulder	Baseline, day 95
Secondary	Change From Baseline to Day 95 in Passive Forward Flexion	Passive range of motion (PROM) measurement using a goniometer to assess forward flexion in the affected shoulder	Baseline, day 95
Secondary	Change From Baseline to Day 95 in Passive Abduction	PROM measurement using a goniometer to assess abduction in the affected shoulder	Baseline, day 95
Secondary	Change From Baseline to Day 95 in Active Internal Rotation	AROM measurement using a goniometer to assess internal rotation in the affected shoulder	Baseline, day 95
Secondary	Change From Baseline to Day 95 in Active External Rotation	AROM measurement using a goniometer to assess external rotation in the affected shoulder	Baseline, day 95
Secondary	Change From Baseline to Day 95 in Passive Internal Rotation	PROM measurement using a goniometer to assess internal rotation in the affected shoulder	Baseline, day 95
Secondary	Change From Baseline to Day 95 in Passive External Rotation	PROM measurement using a goniometer to assess external rotation in the affected shoulder	Baseline, day 95
Secondary	Change From Baseline to Day 95 in Adapted ASES Pain Subscale	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	Baseline, day 95
Secondary	Subject Satisfaction With Treatment at Day 95	Participant assessment of satisfaction with treatment rated as very satisfied, quite satisfied, neither satisfied nor dissatisfied, quite dissatisfied, or very dissatisfied.	Day 95
Secondary	Investigator Assessment of Improvement With Treatment at 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.	Day 95