Inclusion Criteria:
- - Diagnosis of RA and meeting the 2010 American College of Rheumatology/European League
Against Rheumatism classification criteria for RA.
- - Patients between the ages of 18 and 64 years, inclusive, at the Screening Visit.
- - Female patient must be not pregnant, not breast feeding and one of the following
conditions need to apply:
1.
Of non-childbearing potential based on documented surgical treatment or
post-menopausal, meaning patient had spontaneous amenorrhea for at least 12
months without alternate medical cause prior to Screening Visit and follicle
stimulating hormone (FSH) > 40 U/mL at the Screening Visit.
2. Of childbearing potential and using a highly effective method of contraception
and agrees to remain on a highly effective method from the time of signing the
informed consent form (ICF) until 21 days after the last dose.
- - Male patient must agree to stay abstinent or must use together with his female
partner(s) a form of highly effective contraceptive (failure rate of < 1% per year)
from the time of signing the ICF until up to 3 months after the last dose of the study
drug.
- - Nonsmokers (or other nicotine use) as determined by history and by negative urine
cotinine concentration at the Screening Visit and at Admission.
- - Body mass index (BMI) between 18.5 and 32.0 kg/m2, inclusive, at the Screening Visit.
- - Patient is required to have completed a COVID-19 vaccine regimen within no more than 5
months prior to screening to be eligible for the study.
- - Permitted concomitant medications for any reason, must be on a stable dose.
- - Permitted medications include: anti-malarials; nonsteroidal anti-inflammatory drugs
including selective cyclooxygenase-2 inhibitors at approved dosage, and low dose oral
corticosteroids; methotrexate concomitantly with folic acid or folinic acid.
Exclusion Criteria:
- - Female patients who are breastfeeding or have a positive urine pregnancy test.
- - Patients who are unable to eat the prescribed meals during the stay at the site;
vegetarian or vegan.
- - Patient has a history of significant drug allergy.
- - Patient has used a study drug, any prohibited medication(s), over-the-counter (OTC)
medications, vitamins, dietary and herbal supplements.
- - Patient has a history of active suicidal ideation, or any psychiatric disorders that
will affect the patient's ability to participate in the study.
- - Patient has a current or recent history of uncontrolled, clinically significant
infectious, hematological, renal, endocrine, pulmonary, gastrointestinal,
cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
- - Patient with any of the laboratory abnormalities as per reference.
- - Patient has a history of alcohol and/or drug abuse within 24 weeks.
- - Patient has positive results for drug testing and breath alcohol test.
- - Regular consumption of alcohol within 6 months prior to the Screening Visit.
- - Patient has positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis B
core (HBc) antibodies, hepatitis C virus (HCV) antibody, and/or human immunodeficiency
virus (HIV) antibody at Screening Visit.
- - Patient has QT interval corrected for heart rate (QTc) using Fridericia's correction
(QTcF) > 450 ms for males or QTcF > 470 ms for females either at the Screening Visit
or Admission, based on safety 12-lead electrocardiogram (ECG).
Patient has Screening
or Admission ECG with second- or third-degree atrioventricular block, bundle branch
block, arrhythmia (but not sinus arrhythmia or supraventricular premature beats), or
illegible QT interval.
- - Patient has history or evidence of cardiopathy, acute coronary syndrome, hypertrophic
cardiomyopathy, myocarditis or QT prolongation syndrome.
- - Patient is unwilling to abstain from drinks and foods containing alcohol, grapefruit,
or caffeine.
- - Patient has donated blood or experienced acute blood loss (including plasmapheresis)
of greater than 500 mL within 90 days prior to the first dose of study drug.
- - Patients with a known immunodeficiency disorder.
Have a history of a major organ
transplant or hematopoietic stem cell/marrow transplant.
- - Patients with infections requiring treatment or hospitalization within 14 days prior
to the Screening Visit, parenteral antimicrobial therapy within 60 days prior to the
Screening Visit, infected joint prosthesis; history of herpes zoster, active herpes
simplex, or herpes simplex on suppressive therapy.
- - Patient has a chronic hepatic disease or hepatic impairment.
- - Patient has a history of Mycobacterium tuberculosis or positive interferon gamma
release assay for tuberculosis (IGRA-TB) or abnormal chest X-ray (for positive IGRA-TB
patients).
- - Patient has a history of any lymphoproliferative disorder.
- - Patient has a history of COVID-19 unless fully recovered with no sequelae for 14 days.
- - Patient who had a severe course of COVID-19 (extracorporeal membrane oxygenation,
mechanically ventilated).
- - Patient who has recent exposure to someone who has COVID-19 symptoms or positive test
result.
- - Patient who has a positive reverse transcription polymerase chain reaction (RT-PCR)
test for SARS-CoV-2.
- - Patient who has clinical signs and symptoms consistent with SARS-CoV-2 infection.
- - Patients may not receive any live/attenuated vaccine from 30 days prior to the
Screening Visit until Day 14 Follow-up Visit.
- - COVID-19 vaccine should not be given 1 week prior to the Screening Visit.
- - Patients with malignancy or history of malignancy except adequately treated or excised
non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in
situ.
Previous treatment with total lymphoid irradiation.
- - History of recurrent inflammatory joint disease other than RA or history of any other
autoimmune rheumatic diseases other than Sjogren's syndrome.
- - Major surgery within 30 days prior to the Screening Visit or patients with planned
surgery.
- - Patients who have an abnormal chest X-ray for interstitial lung disease (ILD) and/or
patients with history of ILD.
- - History of fainting or family history of sudden death.
- - Patient has any disorder that would interfere with the absorption, distribution,
metabolism or excretion of study drug.
- - Patient has a history of deep vein thrombosis and/or pulmonary embolism.
- - Patient has poor venous access.
