Multicenter Active RA Study

Official Title: “A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Superiority of CRx-102 Over Each of Its Components When Given to Subjects With Active Rheumatoid Arthritis (RA)”

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.

In this trial, CRx-102 will be given to subjects with active RA as an add-on therapy to existing stable doses of DMARDs including MTX, sulfasalazine, hydroxychloroquine, leflunomide or azathioprine. MTX in combination with other DMARDs (e.g., sulfasalazine or hydroxychloroquine) will be permitted to reflect the current standard of care practices within rheumatology.

Intervention(s) in this Clinical Trial

• Drug: CRx-102
  • prednisolone + dipyridamole
• Drug: prednisolone
  • prednisolone (2.7 mg)
• Drug: dipyridamole
  • dipyridamole (180 mg or 360 mg)
• Drug: placebo
  • placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Crx-102 (Dose 1)
• Experimental: 2
  • Crx-102 (Dose 2)
• Active Comparator: 3
  • prednisolone
• Active Comparator: 4
  • dipyridamole
• Placebo Comparator: 5
  • placebo

Primary Measures

• To assess the superiority of CRx-102 compared to prednisolone and dipyridamole using ACR 20 calculated from Baseline to Day 98 in subjects with active RA
  • Time Frame: 98 Days
    Safety Issue?: No

Secondary Measures

• To assess the efficacy of CRx-102 compared to placebo using ACR 20 calculated from baseline to Day 98
  • Time Frame: 98 Days
    Safety Issue?: No

Inclusion Criteria:

• Subject must voluntarily give written informed consent
• Subject must be ≥ 18 years of age
• Subject must have RA (ACR criteria)
• Subject must have at least 4 swollen joints and at least 6 tender joints at screening and baseline (28 joint count)
• Subject must have a CRP > ULN at screening
• Subject must have been on DMARD or DMARD combination (e.g. MTX + hydroxychloroquine) for at least 3 months and be on a stable dose of DMARD(s) for at least 6 weeks prior to screening.
• For MTX subjects: MTX ≥ 7.5 mg weekly (po/sc/im) and willing to take folic acid or follinic acid supplementation
• Subject willing to take concomitant multivitamin or the equivalent of 400 I.U.
• vitamin D and the equivalent of 1000 mg of elemental calcium daily

Exclusion Criteria:

• History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease
• Wheelchair or bed bound
• History of osteoporotic fracture
• History of malignancy within the past 10 years. However, subjects with a history of treated or excised basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate
• 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 cosmetic)
• History of drug or alcohol abuse (as defined by the Investigator)
• History of bleeding disorder
• History of gastrointestinal bleeding within 5 years of screening
• History of severe migraines or headaches
• History of glaucoma
• Active diabetic retinopathy
• Visually compromising cataract
• History of opportunistic infection within the previous 12 months
• Active TB
• 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 HCV antibody
• Positive for HBsAg
• Known positive HIV antibody
• Has a history of hypersensitivity to glucocorticoids and/or dipyridamole
• Treatment with oral, intra-articular, intramuscular, or intravenous glucocorticoids within 6 weeks prior to screening; inhaled glucocorticoid is permitted
• Treatment with any TNFα biologic, anakinra or abatacept within 2 months prior to screening
• Treatment with rituximab
• Treatment with another investigational drug 3 months prior to screening
• Treatment with anticoagulants including: dipyridamole, warfarin, clopidogrel, ticlopidine; Acetylsalicylic acid > 150 mg per day
• Treatment with any concomitant medications that have not been at a stable dose for at least 28 days prior to screening
• ALT or AST laboratory values that exceed 1.5 x ULN
• HgbA1C value of > 7.0%
• Current enrollment in any other study with investigational drug or device
• Female subject who is pregnant or lactating or of child bearing potential and not using acceptable methods of contraception (birth control pills, barriers or abstinence)
• 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Zalicus Industry

Overall Clinical Trial Officials and Contacts

Theresa Podrebarac, MD Study Director Zalicus  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00551707

Study ID Number: CRx-102-007

ClinicalTrials.gov Identifier: NCT00551707

Health Authority: United States: Food and Drug Administration