Multicenter Study to Evaluate CRx-102 vs. Each of Its Components to Treat Active Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: CRx-102 (2.7/180); prednisolone; dipyridamole; placebo; CRx-102 (2.7/360)
Intervention description: prednisolone 2.7 mg plus dipyridamole 180 mg; prednisolone (2.7 mg); dipyridamole 360 mg; placebo; Prednisolone 2.7 mg plus Dipyridamole 360 mg
Intervention MeSH terms: Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Dipyridamole; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CombinatoRx; CRx-102; Rheumatoid Arthritis; Prednisolone; Dipyridamole; ACR20

Summary:

      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.
    

Eligibility criteria:

        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 > 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

        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 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