Inclusion Criteria:
- - Ages 18-75 years (Inclusive).
- - Able to provide written informed consent.
- - Men or women (not nursing or pregnant) who have active RA, defined as symptoms of RA
prior to screening and have satisfied the ACR/EULAR 2010 criteria for the
classification of RA prior to signing the informed consent.
- - Subjects must have a CDAI > 10.0 at screening and have at least 3 tender and at least
3 swollen joints (excluding distal interphalangeal) at screening and at Day 1, based
on the DAS28 joint count.
- - Subjects may be able to be on hydroxychloroquine, methotrexate, and leflunomide.
Sulfasalazine use is not permitted.
- - Subjects may have received targeted synthetic DMARDs such as tofacitinib, baricitinib,
and investigational therapies for RA if they have been washed out for 1 month prior to
screening.
- - Subjects receiving oral corticosteroids must be on a stable dose and at the equivalent
of ≤10 mg prednisone daily for at least 4 weeks.
Subjects may not receive an IM, IV or
IA administration of a corticosteroid within 4 weeks prior to screening visit or
initiation of therapy.
- - All male and female subjects who are biologically capable of having children must
agree to use a medically acceptable method of birth control for the duration of the
study.
All female subjects who are biologically capable of having children must have a
negative pregnancy test result before administration of study drug. Any pregnancy that
occurs in the female partner of a male subject in the trial must be reported if it
occurs at any time during the study.
- - Refrain from receiving any type of vaccinations during the study period (to include
but not limited to influenza, COVID, shingles, tetanus, hepatitis, pneumonia, HPV,
DPT, MMR, and polio).
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).
- - 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.
