A Study to Evaluate the Safety and Efficacy of VIB4920 in Participants With Rheumatoid Arthritis

The purpose of the study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of VIB4920 (formerly MEDI4920) in adult participants with rheumatoid arthritis (RA).

The overall study period will be approximately 337 days. After a screening period of up to 28 days, the participants will be randomized in a 1:1:1:1:1 ratio to receive intravenous dose of VIB4920 and/or placebo in 5 cohorts. Participants are to be followed on their stable background anti-RA therapy at least through 12 weeks (Day 85), at which time rescue therapy may be instituted. All participants will be followed at least through the primary (interim) analysis (Day 113), and those who have not instituted rescue therapy will be followed through Day 309 to determine the duration of clinical response. The primary analysis will be after all participants have completed Day 113, and the final analysis will be after all participants have completed follow-up.

Study with completed results acquired from Horizon in 2024.

Eligibility Criteria:
Principal Inclusion Criteria:

1. Male or female adults, \>= 18 years of age at time of informed consent.
2. Diagnosed with RA according to the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2010 criteria \>= 6 months prior to screening.
3. Disease Activity Score in 28 Joints (DAS 28) using C-reactive Protein (DAS28-CRP) \> 3.2 at screening with \>= 4 tender joint count (TJC) and \>= 4 swollen joint count (SJC) out of the 28 joints assessed for DAS28 present at screening and confirmed present at visit 2 prior to randomization.
4. Positive for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA) at screening, in accordance with criteria at the central laboratory.
5. Treated with methotrexate (MTX), with or without a concomitant conventional disease-modifying anti-rheumatic drug (cDMARD).
6. Agreeing to use of protocol defined contraception methods.

Principal Exclusion Criteria:

1. Prior or current inflammatory joint disease other than RA.
2. Severe interstitial lung disease.
3. Prior receipt of any biologic B-cell-depleting therapy.
4. Receipt of any anti - tumor necrosis factor alpha (TNF-α) biologic agent \< 8 weeks prior to screening.
5. Receipt of any biologic disease-modifying anti-rheumatic drug (bDMARD) with a mechanism of action other than direct TNF-α blockade, \< 12 weeks or \< 5 half-lives of the drug prior to screening.
6. Injectable corticosteroids or treatment with \> 10 mg/day dose of oral prednisolone or equivalent within 4 weeks prior to screening.
7. Previous treatment with anti-cluster of differentiation 40 ligand (CD40L) compounds at any time before randomization.
8. Hepatitis B, hepatitis C, or human immunodeficiency virus infection.
9. Pregnant or lactating or planning to get pregnant during the duration of the study.
10. Evidence of active tuberculosis (TB) or being at high risk for TB.
11. History of more than one episode of herpes zoster in the 12 months prior to screening or any opportunistic infection in the 12 months prior to screening, excluding localized mucocutaneous candidiasis.
12. Receipt of live vaccine or live therapeutic infectious agent within the 4 weeks prior to screening.