R-2487 in Patients With Rheumatoid Arthritis

Exclusion Criteria

• •Pregnancy (females, unless surgically sterile or at least two years post- menopausal must have a negative serum pregnancy test within 14 days prior to receiving the study drug and a negative urine pregnancy test on Study Day 0 before receiving the study drug).
• •Nursing mothers.
• •Subjects with autoimmune disease other than RA \[e.g., psoriasis, systemic lupus erythematosus (SLE), vasculitis, seronegative spondylarthritis, Inflammatory Bowel Disease, Sjogren's syndrome\] or currently active fibromyalgia.
• •Subjects should not receive any of the following medications:
• •Rituximab within 12 months prior to Day 1,
• •Abatacept within 3 months prior to Day 1,
• •Infliximab, Adalimumab, Certolizumab, Tocilizumab, Cyclosporine, or
• •Mycophenolate mofetil within 2 months prior to Day 1, or
• •Etanercept, Anakinra, Immunoglobulin, or blood products within 28 days prior to Day 1
• •Prior immunotherapy, including systemic corticosteroids, such prednisone, biologics, Janus kinase (JAK) inhibitors (such as tofacitinib, baricitinib or upadacitinib), ozanimod, or investigational therapy must have completed at least 5 half-lives or 30 days, whichever is longer, prior to Day 0, unless otherwise specified. In the case of cell-depleting therapies, such as B or T cell depletion, cell counts must have recovered to acceptable or baseline levels (use of licensed agents for indications not listed in the package insert is permitted).
• •Prior history of or current inflammatory joint disease other than RA (such as psoriatic arthritis, gout, reactive arthritis, Lyme disease).
• •Subjects at risk for tuberculosis (TB) defined as follows: Current clinical, radiographic or laboratory evidence of active TB. Chest x-rays (posterior, anterior and lateral) obtained within the 3 months prior to obtaining written informed consent will be permitted but the images must be available and reviewed by the investigator. TB testing (IFN-gamma release assay or PPD) performed in the past month prior to Screening will be accepted; however, a copy of the report must be placed in the subject binder.
• •A history of active TB.
• •Subjects with a positive TB screening test indicative of latent TB including subjects currently being treated for latent tuberculosis infection (LTBI) will not be eligible for the study.
• •Subjects with recent acute infection defined as:
• •Any acute infection within 60 days prior to randomization that required hospitalization or treatment with parenteral antibiotics,
• •Any acute infection within 30 days prior to randomization that required oral antimicrobial or antiviral therapy,
• •Subjects with history of chronic or recurrent bacterial infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis etc.),
• •Subjects with any history of infection of a joint prosthesis or artificial joint,
• •Subjects who have a history of systemic fungal infections (such as histoplasmosis, blastomycosis, or coccidiomycosis),
• •Subjects with history of recurrent herpes zoster (more than 1 episode) or disseminated (more than 1 dermatome) herpes zoster or disseminated herpes simplex, or ophthalmic zoster will be excluded,
• •Symptoms of herpes zoster or herpes simplex must have resolved more than 60 days prior to screening,
• •Subjects with history of primary immunodeficiency.
• •Subjects with history of Human Immunodeficiency Virus (HIV) infection or who tested positive for HIV.
• •Evidence of infection with hepatitis B virus (HBV), hepatitis C virus (C), human immunodeficiency virus (HIV)-1 or HIV-2, or active infection with hepatitis A, as determined by results of testing at screening.
• •Subjects who have a present malignancy or previous malignancy within the last 5 years prior to screening (except documented history of cured non- metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Subjects who had a screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations.
• •Current clinical findings of a history of a demyelinating disorder.
• •New York Heart Association (NYHA) Class III or IV heart failure.
• •Subjects who have undergone a major surgical procedure within the 60 days prior to enrollment.
• •Subjects for whom 5 or more joints cannot be assessed for tenderness or swelling (i.e. due to surgery, fusion, amputation, etc.).
• •Current clinical findings of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, endocrine, neurological, or cerebral disease with laboratory values as following:
• •Hemoglobin level \< 9.0 g/dL,
• •Absolute white blood cell (WBC) count of \<3.0×109/L (\<3000/mm3), or absolute neutrophil count of \<1.2×109/L (\<1200/mm3), or absolute lymphocyte count of \<0.8×109/L (\<800/mm3),
• •Thrombocytopenia, defined by platelet count \<100×109/L (\<100,000/mm3),
• •Chronic kidney disease defined as Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m2, based on the age-appropriate calculation,
• •Proteinuria ≥3+,
• •Total bilirubin (T-bili), aspartate aminotransferase (AST), alanine aminotransferase (ALT) more than 1.5 times upper limit of normal (ULN)
• •Previously diagnosed hepatic cirrhosis (Child Pugh A or higher) or previously diagnosed significant liver fibrosis (\> F3).
• •Any form of vaccination in the last 30 days, to include but not limited to influenza, COVID, shingles, tetanus, hepatitis, pneumonia, HPV, DPT, MMR, and polio.