Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis (StopRA)

Inclusion Criteria:

Subjects who meet all of the following criteria are eligible for enrollment into the study:

• Able and willing to give written informed consent and comply with requirements of the study;
• Age ≥18 years-old at the Screening Visit; and
• Elevation of autoantibody anti-cyclic citrullinated peptide-3 (anti-CCP3) defined by result of anti-CCP3 ≥40 units, at Screening.

Exclusion Criteria:

Subjects who meet any of the following criteria are ineligible to participate in the study:

• Evidence of significant retinal disease that, in the opinion of the examiner, would make identification of potential future retinal toxicity from hydroxychloroquine difficult to evaluate;

• A medical history of inflammatory arthritis (IA) of any type and/or rheumatic disease and immunologic disease(s) that may be associated with IA . These diseases include but are not limited to:

  • rheumatoid arthritis (RA);
  • systemic lupus erythematosus (SLE);
  • seronegative spondyloarthropathies;
  • inflammatory bowel disease;
  • Sjögren's syndrome;
  • polymyalgia rheumatic; or
  • vasculitis.

Note: Crystalline arthropathies are not exclusionary.

• A medical history of:

  • congestive heart failure or functional status of New York Heart Association (NYHA) Class III or higher at the Screening Visit;
  • cardiomyopathy or significant cardiac conduction disorders;
  • chronic liver disease;
  • psoriasis (due to potential for increased risk for flare of skin disease);
  • porphyria;

  • and/or serologic evidence during Screening Visit of chronic infections including, but not limited to, human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV);

    ---Exception: hepatitis C antibody positive subjects are eligible with documentation of:

    • receipt of HCV treatment AND
    • a negative hepatitis C viral load test post-treatment.
  • malignancy within the last 5 years, except for treated basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ cervical cancer Grade I; or
  • alcohol or substance abuse within 1 year of treatment randomization.
• Prior or current systemic treatment with disease modifying anti-rheumatic agents, immunomodulatory agents, or glucocorticoids for IA, other rheumatic diseases, or other immunologic diseases;
• Tetracycline class antibiotic use for autoimmune conditions, taken within 12 months prior to Screening;
• Systemic corticosteroid use for non-IA conditions taken 28 days prior to Screening;
• More than 3 local corticosteroid injections, including but not limited to intra-articular, epidural, and intrabursal injections, during the 3 months prior to randomization;
• A history of a chronic condition that, in the opinion of the investigator, is highly likely to require therapy with systemic corticosteroids (oral or intravenous) within the study period, including but not limited to severe asthma and severe crystalline arthropathy;
• Women who are pregnant, breastfeeding or desire to become pregnant and/or breast feed within the duration of the 12-month treatment phase of the study;
• Women of childbearing potential who are not using or who do not agree to use adequate birth control measures (for example, total abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization, Depo-Provera, or hormonal implants) during the treatment phase of the study;
• An ideal or actual body weight ≤ 24.4 kg (e.g., ≤53 lbs) at Screening Visit;

• Any of the following laboratory abnormalities at the Screening Visit:

  • Serum Creatinine Clearance < 50ml/min (as calculated by the Cockcroft-Gault formula: Creatinine clearance (CrCl)= (140-age) X (Weight in kg) X (0.85 if female) / (72 X Creatinine));
  • Alanine Aminotransferase (ALT) > 2 times the upper limit of normal (ULN);
  • Aspartate Aminotransferase (AST) > 2x the upper limit of normal (ULN);
  • INR ≥ 1.25 if not currently taking anticoagulation therapy;
  • Total white blood count (WBC) < 3.0 x 10^9/L;
  • Platelet count ≤ 150 x10^9/L;
  • Hemoglobin < 11.5g/dL;
  • Absolute Neutrophil Count (ANC) < 2.0 x 10^9/L;

• Evidence of significant retinal disease upon eye examination during the screening period that in the opinion of the examiner would make identification of potential future retinal toxicity from HCQ difficult to evaluate:

  -- Retinal exam results may be applied to evaluations of subject eligibility for up to 6 months after the initial retinal exam.

• When, in the opinion of the study physician, the subject is not a good study candidate.