AA4500 for the Treatment of Adhesive Capsulitis of the Shoulder

NCT ID: NCT01483963

Last Updated: 2017-10-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-30

Study Completion Date

2013-02-28

Brief Summary

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

Detailed Description

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This study is a Phase 2a, open-label, dose-ranging study of the safety and effectiveness 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 30 days before injection of study drug.

Approximately 50 adult women and men are to be enrolled in this study. Following screening and determination of study eligibility, Assignment to Cohorts 1-4 is sequential. Subjects assigned to Cohorts 1 through 4 may receive up to 3 injections of AA4500 according to cohort assignment. Each injection will be separated by a minimum of 21 days. Subjects assigned to Cohort 5 will receive home shoulder exercises only, while subjects assigned to Cohorts 1-4 will receive AA4500 and home shoulder exercises. Subjects in Cohort 5 will be offered physical therapy sessions for a period of 2 months following completion of the study.

Dosing will range from 0.29 mg to 0.58 mg with varying volumes.

Conditions

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Adhesive Capsulitis Frozen Shoulder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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AA4500 0.29 mg/1 mL

Up to three injections

Group Type EXPERIMENTAL

AA4500 0.29 mg/1 mL

Intervention Type BIOLOGICAL

treatment of adhesive capsulitis

Shoulder exercises

Intervention Type OTHER

Home shoulder exercises, minimum of 3 times per day

AA4500 0.58 mg/2 mL

Up to three injections

Group Type EXPERIMENTAL

AA4500 0.58 mg/2 mL

Intervention Type BIOLOGICAL

treatment of adhesive capsulitis

Shoulder exercises

Intervention Type OTHER

Home shoulder exercises, minimum of 3 times per day

AA4500 0.58 mg/1 mL

Up to three injections

Group Type EXPERIMENTAL

AA4500 0.58 mg/1 mL

Intervention Type BIOLOGICAL

treatment of adhesive capsulitis

Shoulder exercises

Intervention Type OTHER

Home shoulder exercises, minimum of 3 times per day

AA4500 0.58 mg/0.5 mL

Up to three injections

Group Type EXPERIMENTAL

AA4500 0.58 mg/0.5 mL

Intervention Type BIOLOGICAL

treatment of adhesive capsulitis

Shoulder exercises

Intervention Type OTHER

Home shoulder exercises, minimum of 3 times per day

Shoulder exercises

Home shoulder exercises for 64 days

Group Type OTHER

Shoulder exercises

Intervention Type OTHER

Home shoulder exercises, minimum of 3 times per day

Interventions

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AA4500 0.29 mg/1 mL

treatment of adhesive capsulitis

Intervention Type BIOLOGICAL

AA4500 0.58 mg/2 mL

treatment of adhesive capsulitis

Intervention Type BIOLOGICAL

AA4500 0.58 mg/1 mL

treatment of adhesive capsulitis

Intervention Type BIOLOGICAL

AA4500 0.58 mg/0.5 mL

treatment of adhesive capsulitis

Intervention Type BIOLOGICAL

Shoulder exercises

Home shoulder exercises, minimum of 3 times per day

Intervention Type OTHER

Other Intervention Names

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collagenase clostridium histolyticum XIAFLEX XIAPEX collagenase clostridium histolyticum XIAFLEX XIAPEX collagenase clostridium histolyticum XIAFLEX XIAPEX collagenase clostridium histolyticum XIAFLEX XIAPEX

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Endo Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Neil H Shusterman, MD FACP

Role: STUDY_DIRECTOR

Endo Pharmaceuticals

Locations

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Alabama Orthopaedic Center - Research

Birmingham, Alabama, United States

Site Status

HOPE Research Institute

Phoenix, Arizona, United States

Site Status

Tucson Orthopaedic Institute

Tucson, Arizona, United States

Site Status

OrthoArkansas

Little Rock, Arkansas, United States

Site Status

CORE Orthopaedic Medical Center

Encinitas, California, United States

Site Status

Triwest Research Associates

La Mesa, California, United States

Site Status

Advent Clinical Research

Pinellas Park, Florida, United States

Site Status

Rockford Orthopedic Associates

Rockford, Illinois, United States

Site Status

The Indiana Hand to Shoulder Center

Indianapolis, Indiana, United States

Site Status

Stony Brook University Medical Center

Stony Brook, New York, United States

Site Status

David R. Mandel, MD, Inc.

Cleveland, Ohio, United States

Site Status

Health Research Institute

Oklahoma City, Oklahoma, United States

Site Status

Blair Orthopedic Associates, Inc.

Altoona, Pennsylvania, United States

Site Status

Alpha Clinical Research, LLC

Clarksville, Tennessee, United States

Site Status

Basin Orthopedic Surgical Specialists

Odessa, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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AUX-CC-870

Identifier Type: -

Identifier Source: org_study_id