Clinical trial NCT02006719: Clinical Study for the Treatment of Adhesive Capsulitis of the Shoulder
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adhesive Capsulitis
Frozen Shoulder
Keywords: Adhesive Capsulitis
Frozen Shoulder
Shoulder Range of Motion limitation
Shoulder Pain
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-12-10
Enrollment: 322
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline to Day 95 in Active Forward Flexion
timeFrame: Baseline, day 95
Secondary outcomes:
measure: Change From Baseline to Day 95 in Adapted American Shoulder and Elbow Surgeons (ASES) Function Subscale
timeFrame: Baseline, day 95
measure: Change From Baseline to Day 95 in Pain With Movement Using 11-point Numeric Rating Scale (NRS)
timeFrame: Baseline, day 95
measure: Change From Baseline to Day 95 in Active Abduction
timeFrame: Baseline, day 95
measure: Change From Baseline to Day 95 in Passive Forward Flexion
timeFrame: Baseline, day 95
measure: Change From Baseline to Day 95 in Passive Abduction
timeFrame: Baseline, day 95
measure: Change From Baseline to Day 95 in Active Internal Rotation
timeFrame: Baseline, day 95
measure: Change From Baseline to Day 95 in Active External Rotation
timeFrame: Baseline, day 95
measure: Change From Baseline to Day 95 in Passive Internal Rotation
timeFrame: Baseline, day 95
measure: Change From Baseline to Day 95 in Passive External Rotation
timeFrame: Baseline, day 95
measure: Change From Baseline to Day 95 in Adapted ASES Pain Subscale
timeFrame: Baseline, day 95
measure: Subject Satisfaction With Treatment at Day 95
timeFrame: Day 95
measure: Investigator Assessment of Improvement With Treatment at Day 95
timeFrame: Day 95
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Orthopaedic Center-Research
state: Alabama
city: Mobile
country: United States
facility: Coastal Clinical Research
state: Alabama
city: Phoenix
country: United States
facility: Arizona Research Center, Inc.
state: Arizona
city: Carlsbad
country: United States
facility: Advance Med Clinical Research
state: California
city: El Cajon
country: United States
facility: Triwest Research Associates
state: California
city: Encinitas
country: United States
facility: Core Orthopedic Medical Center
state: California
city: Murrieta
country: United States
facility: Temecula Rheumatology & Internal Medicine
state: California
city: Santa Clarita
country: United States
facility: Clearview Medical Research
state: California
city: Englewood
country: United States
facility: Colorado Orthopedic Consultants, PC
state: Colorado
city: DeLand
country: United States
facility: Florida Research Associates
state: Florida
city: Fort Lauderdale
country: United States
facility: Shrock Orthopedic Research, LLC
state: Florida
city: Orlando
country: United States
facility: Jewett Orthopedic Clinic
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Marietta
country: United States
facility: Non-Surgical Orthopedics, P.C. / Georgia Institute for Clinical Research, LLC
state: Georgia
city: Boise
country: United States
facility: Injury Care Medical Center
state: Idaho
city: Rockford
country: United States
facility: Rockford Orthopedic Associates
state: Illinois
city: Rockford
country: United States
facility: Rockford Orthopedics Associates
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hand to Shoulder Center
state: Indiana
city: Wichita
country: United States
facility: PRN of Kansas
state: Kansas
city: Lexington
country: United States
facility: Central Kentucky Research Associates
state: Kentucky
city: Gretna
country: United States
facility: Bone and Joint Clinic
state: Louisiana
city: Metairie
country: United States
facility: MedPharmics, LLC
state: Louisiana
city: Wheaton
country: United States
facility: Arthritis and Rheumatism Associates, PC
state: Maryland
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Las Vegas
country: United States
facility: Nevada Orthopedic & Spine Center
state: Nevada
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center (SUNY)
state: New York
city: Durham
country: United States
facility: Triangle Orthopedic Associates, PA
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Bend
country: United States
facility: The Neuromusculoskeletal Center of the Cascades d.b.a. The Center
state: Oregon
city: Altoona
country: United States
facility: Blair Orthopedic Associates, Inc.
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Penn Orthopaedics
state: Pennsylvania
city: Bedford
country: United States
facility: Texas Orthopedic Specialist
state: Texas
city: Houston
country: United States
facility: Centex Studies
state: Texas
city: Arlington
country: United States
facility: Commonwealth Orthopaedics & Rehabilitation
state: Virginia
city: Danville
country: United States
facility: Danville Orthopedic Clinic, Inc.
state: Virginia
city: Richmond
country: Australia
facility: Sports Medicine Professionals
state: Victoria
city: NSW
country: Australia
facility: Hunter Clinical Research
city: NSW
country: Australia
facility: Royal Prince Alfred
city: NSW
country: Australia
facility: St George Hospital
city: Queensland
country: Australia
facility: Peninsula Private Hospital
city: Queensland
country: Australia
facility: QPharm
city: Tasmania
country: Australia
facility: Menzies Research Institute
city: VIC
country: Australia
facility: Emeritus Research
city: VIC
country: Australia
facility: Epworth Hospital
city: VIC
country: Australia
facility: Repatriation Hospital
city: WA
country: Australia
facility: Hand and Upper Limb Centre
Study officials:
affiliation: Endo Pharmaceuticals
name: Neil H Schusterman, MD FACP
role: STUDY_DIRECTOR
References: