A Safety Study Of BMP-655/ACS As An Adjuvant Therapy For Treatment Of Rotator Cuff Tears

Study Overview
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Brief Summary
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Subjects undergoing an open surgical repair for their torn Rotator Cuff (RC) will be consented, screened, and enrolled in the study if they meet all eligibility criteria. At the time of open surgical repair, subjects who are randomized to receive the test article in addition to the Standard of Care (SOC) will be hospitalized and have a single dose of BMP-655/ACS surgically implanted at the site of tendon attachment to bone. Subjects who are randomized to receive SOC alone will receive no test article. Following surgery, subjects will be prescribed a rehabilitation plan. Subjects will then complete 9 follow-up visits beginning 24 hours after surgery and continuing through 52 weeks.

Official Title
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A Phase 1, Randomized, Open-Label, Standard Of Care Control, Dose-Escalating, Multicenter, Safety Study Of BMP-655/ACS As An Adjuvant Therapy For Treatment Of Full-Thickness Rotator Cuff Tears Treated By Means Of An Open Surgical Repair

Conditions
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Rotator Cuff Tear

Intervention / Treatment
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* Biological: BMP-655/ACS+Standard of care or Standard of care
* Biological: BMP-655/ACS+Standard of care or Standard of care
* Biological: BMP-655/ACS+Standard of care or Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese male subjects and surgically sterile or postmenopausal Japanese female subjects between the ages of 25 and 75 years. without tears of the subscapularis or labral pathology requiring surgical repair, as estimated on closed magnetic resonance imaging (MRI) within 3 months before surgery. In the shoulder under study, subjects should be able to achieve a passive range of motion (ROM), which is at least 150 degrees in forward elevation (flexion), abduction, and elevation in the scapular plane (scapular abduction). Subjects should have at least 40 degrees of passive ROM in external rotation. In the contralateral shoulder, subjects should be able to achieve active ROM, which is at least 150 degrees in forward elevation (flexion), abduction, and elevation in the scapular plane (scapular abduction). Subjects should have at least 40 degrees of active ROM in external rotation. Exclusion Criteria: Subjects who have had previous surgical intervention to the shoulder joint under study (eg, shoulder arthroscopy, acromioplasty, previous RCR, fracture). Subjects with stage 3 or 4 fatty infiltration (according to the Goutallier grading scale) of their RC muscles on MRI taken within 3 months prior to surgical repair or subjects with moderate or severe degenerative glenohumeral arthritis (according to the Samilson and Prieto arthrosis grading scale ), avascular necrosis, calcific tendonitis, chondrocalcinosis, hypertrophic osteoarthropathy, or Paget disease of the shoulder under study or any bone abnormalities (eg, HO, previous fracture) as confirmed on a radiograph within 3 months prior to surgical repair. Subjects with rheumatologic conditions (eg, rheumatoid arthritis, ankylosing spondylitis) affecting the shoulder joints, or autoimmune disorders. Subjects treated with more than 3 corticosteroid injections in the shoulder under study within 1 year prior to planned surgery or subjects treated with any corticosteroid injection in the shoulder under study within 3 months prior to planned surgery or subjects currently receiving oral corticosteroids or taking them within the past 3 months. Subjects who are either unwilling or unable (eg, because of claustrophobia or the presence of an automatic cardioverter defibrillator) to undergo examination with closed MRI. Subjects with any other major illness/condition that will substantially increase the risk associated with the subject's participation in and completion of the study.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: BMP-655/ACS+Standard of care or Standard of care<br>* BMP-655/ACS 0.015mg/mL<br>|
| Experimental: 2<br> | Biological: BMP-655/ACS+Standard of care or Standard of care<br>* BMP-655/ACS 0.05mg/mL<br>|
| Experimental: 3<br> | Biological: BMP-655/ACS+Standard of care or Standard of care<br>* BMP-655/ACS 0.15mg/mL or 0.025mg/mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety and tolerability of 3 concentrations of BMP-655/ACS in Japanese subjects with full-thickness RCTs treated by means of an open surgical repair. |  | 12, 26 and 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the feasibility of implanting BMP-655/ACS through an open surgical procedure in Japanese subjects and detect circulating levels of BMP-655 in the blood of Japanese subjects. |  | 52 weeks |