Resumen

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 Osteoarthritis (OA) and Rheumatoid Arthritis (RA). In this trial, CRx-102 will be given to subjects with active RA as an add-on therapy to existing stable doses of Disease Modifying Anti-Rheumatic Drugs (DMARDs) including methotrexate (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.

Descripción detallada

The study was discontinued before the enrollment objective was met. Preliminary review of the efficacy dataset revealed that the efficacy dataset was not robust enough to support an extensive formal efficacy analysis as described in the SAP. Therefore, only the CRP values over time and the percent change in C-reactive protein (CRP) values in the As-Treated population were calculated.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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 \> Upper Limit of Normal 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 folinic 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

Criterios de exclusión

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 Tuberculosis (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 Hepatitis C virus (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 tumor necrosis factor-alpha (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
Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) laboratory values that exceed 1.5 x ULN
HbA1C 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

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)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

CRx-102 (2.7/180)

prednisolone

dipyridamole

placebo

CRx-102 (2.7/360)

Ubicaciones

Patrocinadores