CRx-102 Osteoarthritis Multicenter Evaluation Trial

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy of CRx-102 in Subjects With Symptomatic Knee Osteoarthritis and Optional One-Year Extension

CRx-102 is a synergistic combination drug candidate containing the cardiovascular drug dipyridamole and a very low dose of the glucocorticoid prednisolone. CRx-102 is believed to work through a novel mechanism of action in which dipyridamole selectively amplifies the anti-inflammatory and immunomodulatory activities of the glucocorticoid without replicating the dose-dependent adverse effects.

CRx-102 has been associated with clinical benefit in proof of concept studies in subjects with hand OA and RA. This is the first study to explore the efficacy of CRx-102 in knee OA. It is considered a dose-finding study and will also compare the potential benefits of CRx-102 treatment to both prednisolone administered alone and to placebo in this indication.

Inclusion Criteria:

• Subject must voluntarily give written informed consent
• Subject must be ≥ 40 years of age
• Knee pain for at least 6 months requiring NSAIDs or Coxibs for analgesia on the majority of days (≥ 15 days) during the preceding month
• WOMAC pain score when walking on a flat surface (question #1) between 30-80 mm at Screening with at least a 10 mm increase following NSAID or Coxib discontinuation during the Screening period
• Radiographic evidence of knee OA (Kellgren-Lawrence grade 2 or 3)
• Functional class I, II, or III according to the American Rheumatism Association
• Subject willing to take a multivitamin or the equivalent of at least 400 IU vitamin D and the equivalent of at least 1000 mg of elemental calcium daily

Exclusion Criteria:

• Predominant patellofemoral disease or clinically significant trauma to index knee
• History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, osteoporotic and/or other major disease
• History of malignancy within the past 10 years (except for excised or treated basal cell or fewer than 3 squamous cell skin carcinomas)
• History of lymphoma or chronic leukemia
• Moles or lesions that are currently undiagnosed, but are suspicious for malignancy
• Surgery within the previous 3 months (except for minor dental, and/or cosmetic procedures)
• History of drug or alcohol abuse (as defined by the Investigator)
• History of bleeding disorder
• History of GI bleeding within 5 years of Screening
• History of severe migraines or headaches
• History of glaucoma
• Visually compromising cataract
• Active diabetic retinopathy
• History of osteoporotic fracture
• History of opportunistic infection
• Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 months prior to Screening
• Fever or symptomatic viral or bacterial infection within 2 weeks prior to Screening
• Positive for hepatitis C (HCV) antibody
• Positive for hepatitis B surface antigen (HBsAg)
• Known positive history for human immunodeficiency virus (HIV) antibody
• Surgery on the index knee within 1 year of Screening
• History of hypersensitivity to steroids or dipyridamole
• Treatment with oral, intramuscular, or intravenous glucocorticoids within 6 weeks prior to Screening; intra-articular glucocorticoids within 10 weeks prior to Screening; inhaled glucocorticoid is permitted
• Treatment with injectable hyaluronic acid within 3 months of Screening
• Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 30 days prior to Screening
• Treatment with NSAIDs (oral or topical), Coxibs or topical capsaicin
• Treatment with anticoagulants including: dipyridamole, warfarin, clopidogrel, ticlopidine, or ASA > 81 mg per day
• Treatment with any concomitant medications that have not been at a stable dose for at least 28 days prior to Screening
• Treatment for osteoporosis such as bisphosphonates (e.g., Fosamax®, Actonel®), or teriparatide (e.g., Forteo®), or calcitonin (e.g., Miacalcin, Calcimar) must be at stable dosages for at least 3 months prior to Screening
• ALT or AST laboratory values >1.5 X the ULN
• HgbA1c value of >7.0%
• Current enrollment in any other study with investigational drug or device
• Female subject who is pregnant or lactating
• Unwilling or unable to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's return for follow-up visits on schedule
• Other unspecified reasons that, in the opinion of the Investigator or sponsor make the subject unsuitable for enrollment