Clinical trial NCT01111045: Dose Finding Study of Bone Morphogenetic Protein 7 (BMP-7) in Subjects With Osteoarthritis (OA) of the Knee
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis of the Knee
Lead sponsor: Stryker Biotech
Sponsor class: INDUSTRY
First posted: 2010-04-27
Enrollment: 355
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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:

  1. ALT and AST ≥2.5x ULN
  2. Hemoglobin \<11.5 g/dL (Female) or \<13.2 g/dL (Male)
  3. WBC \<3500 cells/mm3
  4. Lymphocyte count ≤1000 cells/mm3
  5. Serum creatinine ≥1.5 x ULN
  6. 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.

Primary outcomes:
measure: Change from baseline in Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain subscale.
timeFrame: Baseline, and at 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Arizona Arthritis and Rheumatology Research
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Arthritis Center
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center, Center for Aging
state: California
city: Tustin
country: United States
facility: Robin Dore, MD, Inc
state: California
city: Boulder
country: United States
facility: Boulder Medical Center, PC
state: Colorado
city: Boca Raton
country: United States
facility: Rheumatology Associates of S. Florida
state: Florida
city: Palm Harbor
country: United States
facility: The Arthritis Center
state: Florida
city: Stuart
country: United States
facility: Rheumatology Associates
state: Florida
city: Chicago
country: United States
facility: Northwestern Center for Clinical Research
state: Illinois
city: Chicago
country: United States
facility: Apex Medical Research, AMR, Inc
state: Illinois
city: Morton Grove
country: United States
facility: Illinois Bone and Joint Institute
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Medical Center
state: Maryland
city: Cumberland
country: United States
facility: Klein & Associates, MD, PA
state: Maryland
city: Frederick
country: United States
facility: Arthritis and Osteoporosis Center of Maryland
state: Maryland
city: Kansas City
country: United States
facility: The Center for Pharmaceutical Research, PC
state: Missouri
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Mayfield Village
country: United States
facility: David R. Mandel, MD, Inc.
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: West Reading
country: United States
facility: Clinical Research Center of Reading
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Houston
country: United States
facility: Houston Institute for Clinical Research
state: Texas
city: Houston
country: United States
facility: Houston Medical Research Associates
state: Texas
city: Tacoma
country: United States
facility: Tacoma Center for Arthritis Research
state: Washington
Study officials:
References: