Inclusion Criteria:
1. Participant or legally authorized representative must be able to understand and
provide informed consent. 2. Adult 18-75 years of age. 3. Diagnosed with RA by fulfilling the ACR/EULAR 2010 Classification Criteria for RA ≥
6 months prior to screening (Appendix 9)
4. Documented positive test for rheumatoid factor (RF) and/or anti-cyclic citrullinated
peptide antibody (ACPA)
5. SDAI ≥ 17. 6. At least 4 tender and 4 swollen joints by a 44 joint count (Appendix 5)
7. Receiving treatment with an FDA-approved TNFi (including biosimilars) that is dosed
subcutaneously at an FDA-approved dosing regimen for at least 12 weeks.
8. Willing to continue or discontinue treatment with their current TNFi at the same
dose depending upon study arm assignment. 9. If treated with leflunomide, sulfasalazine, or hydroxychloroquine, must be taking a
stable dose for at least 12 weeks. 10. If treated with methotrexate, must be taking a stable dose for at least 12 weeks.
The following exceptions are permitted within the 12 weeks prior to screening:
1. Holding methotrexate after COVID-19 vaccination as per American College of
Rheumatology guidance (https://rheumatology.org/)
2. Holding methotrexate for 1 or 2 weeks after influenza vaccination. 11. All participants who engage in sexual activity that could lead to pregnancy must
agree to use abstinence or an FDA-approved contraception for the duration of the
study to prevent pregnancy.
Exclusion Criteria:
1. Inability or unwillingness to give written informed consent or comply with the study
protocol. 2. Prior or ongoing systemic inflammatory or autoimmune disease (other than RA and
secondary Sjögren's syndrome) requiring or potentially requiring other systemic
immunomodulatory therapy during the 40-week study period. 3. Use of glucocorticoid and/or disease-modifying therapies as specified below:
1. Prior treatment with any B cell depleting therapy (e.g., rituximab)
2. History of treatment with more than two TNFi, including the treatment with the
current TNFi. Treatment with an originator (reference product) TNFi (e.g.,
etanercept or adalimumab) and its respective biosimilar would count as a single
TNFi if treatment has been continuous and without interruption by more than 90
days when switching between the orginator TNFi and biosimilar TNFi.
3. Treatment with other biologic therapy (i.e., not targeting TNF-α), including
abatacept, tocilizumab, or sarilumab within the previous 12 weeks. 4. Treatment with a JAK inhibitor within the previous 12 weeks. 5. Concurrent use of methotrexate and leflunomide in combination. 6. Prednisone > 10 mg a day or equivalent glucocorticoid use within the previous 4
weeks. 7. Intramuscular, intra-articular, or intravenous glucocorticoids within the
previous 4 weeks. 8. Other immunomodulatory medications within the previous 12 weeks except for
methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine. 4. Lack of any subjective or objective clinical response (i.e., complete non-responder)
to treatment with the current TNFi, in the opinion of the study investigator based
on available documentation in the medical record and/or history provided by the
patient and/or referring rheumatologist. 5. Use of an investigational agent including VIB4920 in the past 30 days or 5
half-lives, whichever is longer. 6. History of a severe allergy, hypersensitivity reaction, or infusion reaction to any
component of the VIB4920 formulation. 7. History of Felty's syndrome. 8. History of interstitial lung disease with FVC < 70% predicted, DLCO < 70% predicted,
or requiring supplemental oxygen. 9. Arterial or deep venous thromboembolism including pulmonary embolism in the prior
two years. 10. Infection:
a. Evidence of current or prior infection with hepatitis B, as indicated by a
positive test for the hepatitis B surface antigen (HBsAg) or a positive test for the
hepatitis B core antibody (HBcAb) b. Positive HCV serology unless treated with an
anti-viral regimen resulting in a sustained virologic response (undetectable viral
load 24 weeks after cessation of therapy) c. Evidence of HIV infection d. Evidence
of active tuberculosis, untreated or incompletely treated latent tuberculosis, or
recent close contact with a person who has active tuberculosis e. Positive
QuantiFERON-TB Gold, QuantiFERON-TB Gold Plus, or T-SPOT-TB test without history of
previous treatment for active or latent TB f. Indeterminate QuantiFERON-TB Gold,
QuantiFERON-TB Gold Plus, or T-SPOT.TB test which remains indeterminate on repeat
testing, and any of the following additional required screening which indicates an
increased risk of TB infection: i. History of tuberculosis exposure ii. History of
travel to an area where tuberculosis is endemic iii. Findings on chest radiograph
suggestive of prior exposure to tuberculosis (e.g., granulomas or apical scarring)
obtained at screening or within the past 3 months iv. Positive purified protein
derivative (PPD) skin test for tuberculosis obtained in the past 3 months, either
obtained at screening or within the past 3 months v. Prior history of a positive
QuantiFERON-TB Gold, QuantiFERON-TB Gold Plus, T- SPOT.TB, or purified protein
derivative (PPD) test without history of previous treatment for latent TB g.
Symptoms of presumed or documented SARS-CoV-2 infection in the past 30 days h. More
than one episode of herpes zoster in the past 12 months. i. An opportunistic infection in the past 12 months j. Acute or chronic infection,
including current use of suppressive systemic anti-microbial therapy for chronic or
recurrent bacterial or fungal infection, hospitalization for treatment of infection
in the past 60 days, or parenteral anti-microbial (including anti-bacterial,
anti-viral, or anti-fungal agents) use in the past 60 days for infection k. History
of bronchiectasis with recurrent pulmonary infections. 11. History of a primary immunodeficiency disorder. 12. Vaccination with a live vaccine within the past 30 days. 13. Women who are pregnant or breast-feeding. 14. White Blood Cell (WBC) count < 3.0 x 103/μl. 15. Absolute neutrophil count < 1.5 x 103/μl. 16. Hemoglobin < 9 g/dL. 17. Platelet count < 100 x 103/μl. 18. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2x the upper
limit of normal (ULN)
19. History of malignant neoplasm within the last 5 years, except for basal cell or
squamous cell carcinoma of the skin treated with local resection only or carcinoma
in situ of the uterine cervix treated locally. 20. Current, diagnosed mental illness or current, diagnosed or self-reported drug or
alcohol abuse that, in the opinion of the investigator, would interfere with the
participant's ability to comply with study requirements. 21. Any new or uncontrolled condition occurring within the past 12 weeks which, in the
judgment of the investigator, could interfere with participation in the trial (e.g.,
diabetes mellitus with HbA1c ≥ 9.0%, myocardial infarction, or stroke)
22. Past or current medical problems or findings from physical examination or laboratory
testing that are not listed above, which, in the opinion of the investigator, may
pose additional risks from participation in the study, may interfere with the
participant's ability to comply with study requirements, or that may impact the
quality or interpretation of the data obtained from the study. 23. Inability to comply with study and follow-up procedures
