Dose Finding Study of Bone Morphogenetic Protein 7 (BMP-7) in Subjects With Osteoarthritis (OA) of the Knee

Study Overview
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Brief Summary
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The objectives of the study are to evaluate the safety and efficacy of intraarticular BMP-7 for the treatment of osteoarthritis of the knee.

Official Title
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A Phase 2, Double Blind, Randomized, Placebo-Controlled, Proof of Concept, Dose Finding Study of Intraarticular Bone Morphogenetic Protein (BMP-7) in Subjects With Osteoarthritis (OA) of the Knee

Conditions
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Osteoarthritis of the Knee

Intervention / Treatment
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* Drug: Bone morphogenetic protein 7
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory with a diagnosis of OA of the knee with symptoms for at least 6 months and pain on the majority of days in the last 30 days. Symptoms must include knee joint pain. A male or female adult age >40 years female subjects of childbearing potential must have a negative serum pregnancy test during screening and a negative urine pregnancy test on the day of injection Radiographic evidence of at least one tibiofemoral osteophyte and Osteoarthritis Research Society International (OARSI) Atlas joint space narrowing grade of 1 or 2 in the index knee WOMAC pain score of >8 at screening and baseline Able to comply with the study and give informed consent Able to read, write and understand English Exclusion Criteria: A requirement for treatment with opioids for pain relief. Unwilling to abstain from NSAIDs and/or other analgesic medications for 48 hours and acetaminophen for 24 hours prior to pain assessments during the study. Subjects taking low dose aspirin for cardiovascular health may remain on their stable dose throughout the study. Using a handicap assistance device (i.e., cane, walker) >50% of the time. Undergoing new physical therapy or participating in a weight loss or exercise program that has not been stable for at least 3 months prior to screening visit 1 and will not remain stable during their participation in the study. History of arthroscopic or open surgery to the index knee in the past 12 months or planned surgery during study. History of joint replacement surgery (index knee). Received corticosteroid, short acting hyaluronic acid, or other intraarticular injections of the index knee within 3 months of screening and/or not willing to abstain from treatments for the duration of the study Received long acting hyaluronic acid injection of the index knee within 6 months of screening and/or not willing to abstain from treatments for the duration of the study. History in the past 10 years of reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis, amyloidosis or fibromyalgia. Clinical signs and symptoms of active knee infection or radiographic evidence of crystal disease other than chondrocalcinosis (i.e., gout and CPPD). A history of abnormal laboratory results ≥2.5 x ULN indicative of any significant medical disease, which in the opinion of the investigator, would preclude the subjects participation in the study Any of the following abnormal laboratory results during screening: ALT and AST ≥2.5x ULN Hemoglobin <11.5 g/dL (Female) or <13.2 g/dL (Male) WBC <3500 cells/mm3 Lymphocyte count ≤1000 cells/mm3 Serum creatinine ≥1.5 x ULN Platelet count below the central laboratory lower limit of normal. History of malignancy in the past ten years (<10 years), with the exception of resected basal cell, squamous cell of the skin, resected cervical atypia or carcinoma in situ. Significant hip pain, ipsilateral to the index knee that may interfere with assessments of index knee pain Skin breakdown at the knee where the injection would take place A known or clinically suspected infection with human immunodeficiency virus (HIV), or hepatitis C or B viruses Participated within 3 months or will participate concurrently in another investigational drug or vaccine study A history of drug or alcohol dependence or abuse in the past 3 years Previous treatment with BMP-7 or any bone morphogenetic protein A female with reproductive capability who is unwilling to use birth control for the duration of the study and/or intends to conceive within 12 months of dosing. Other serious, non-malignant, significant, acute or chronic medical or psychiatric illness that, in the judgment of the investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study.

Ages Eligible for Study
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Minimum Age: 40 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>0.03 mg/ml BMP-7, single intraarticular knee injection | Drug: Bone morphogenetic protein 7<br>* Comparison of different doses of the drug via single intraarticular knee injection<br>|
| Active Comparator: Arm 2<br>0.1 mg/ml BMP-7, single intraarticular knee injection | Drug: Bone morphogenetic protein 7<br>* Comparison of different doses of the drug via single intraarticular knee injection<br>|
| Active Comparator: Arm 3<br>0.3 mg/ml BMP-7, single intraarticular knee injection | Drug: Bone morphogenetic protein 7<br>* Comparison of different doses of the drug via single intraarticular knee injection<br>|
| Placebo Comparator: Arm 4<br>1 ml placebo, single intraarticular knee injection (control) | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain subscale. |  | Baseline, and at 24 weeks |