A Phase 1, Double-Blind, Randomized, Single Dose Escalation Safety Study of Intra-articular OP-1 in Subjects With Osteoarthritis of the Knee (Knee OA)
The purpose of this research study is to investigate the safety and tolerability of OP-1 when it is injected into the knee joint of patients who have osteoarthritis on the knee.
Osteoarthritis of the Knee
Drug: Intra-articular Injection of OP-1 to affected knee
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
|Official Title:||A Phase 1, Double-Blind, Randomized, Single Dose Escalation Safety Study of Intra-articular Osteogenic Protein-1 OP-1 in Subjects With Osteoarthritis of the Knee|
- Determine safety and tolerability as well as dose limiting toxicity (DLT) and maximal tolerated dose (MTD) of intraarticular OP-1
- Determine the proportion of patients with 20%, 50%, and 70% improvement in the Western Ontario and McMaster (WOMAC) pain, and function subscales at 4, 8, 12, and 24 weeks.
- Determine the change from baseline to 4, 8, 12, and 24 weeks in the pain, other symptoms, function in daily living, function in sports and recreation and knee related quality of life subscales of the Knee and Osteoarthritis Outcome Score (KOOS) survey.
- Determine the change from baseline to 4, 8, 12, and 24 weeks in the patient's global assessment and disease status and physician's global assessment and disease status using the 100-mm visual-analogue scale (VAS).
- Quality of life measured by the Short Form (SF)-36 at baseline and 4, 8,12 and 24 weeks
- Amount of rescue medications required at 4, 8, 12 and 24 weeks
- Knee cartilege and surrounding saft tissue changes by magnetic resonance imaging (MRI) of the index knee and proteoglycan content by delayed gadolinium enhanced MRI of cartilage (dGEMRIC)
- Analysis of efficacy data using the Outcome Measures in Arthritis Clinical Trials -Osteoarthritis Research Society (OMERACT-OARSI) Responder Index
- Blood levels of OP-1
|Study Start Date:||March 2007|
|Study Completion Date:||November 2008|
Subjects with OA will be recruited and informed consent obtained. During a screening period lasting 1 to 28 days, subjects will undergo medical and arthritis history, physical examination, collection of concomitant medications, KOOS (which contains the WOMAC questionnaire), SF-36 and global 100 mm VAS assessments, have samples obtained for urinalysis, hematology, chemistry, immunology and serum and plasma for future biomarker testing, ECG, bilateral knee x-rays and MRI of the index knee at selected sites. Subjects who meet all of the inclusion criteria and none of the exclusion criteria will be randomized into the first cohort of 8 subjects to receive either 1.0 mL lactose (placebo) (2 subjects) or 1.0 mL OP-1 (6 subjects) intraarticularly using ultrasound or fluoroscopy guidance in an outpatient setting on day 1. Each cohort will consist of 8 treated patients, with treatment allocation in a 3:1 active-to-lactose (placebo) ratio. After an observation period of at least one hour, subjects will be released and contacted via telephone on Day 2 to query for AEs and concomitant medications. Additional follow-up visits will be done on days 7, 14, 28, 56, 84 and 168 (weeks 1, 2, 4, 8, 12 and 24) and safety and efficacy parameters evaluated according to the Schedule of Events. When a minimum of 4 weeks have elapsed since the last patient of the current cohort has been treated, all safety data will be collected and reviewed by the Principal Investigators and the Sponsor. The safety review will be conducted to ensure the demonstrated safety profile of OP-1 is acceptable for the treated patients. Only after the current dose level has been judged to be safe will dose escalation to the next dosing cohort occur.
|United States, Massachusetts|
|Boston University Medical Center|
|Boston, Massachusetts, United States, 02118-2526|
|Tufts-New England Medical Center|
|Boston, Massachusetts, United States, 02111|
|United States, North Carolina|
|University of orth Carolina School of Medicine|
|Chapel Hill, North Carolina, United States, 27599-7280|