Trial Outcomes & Findings for CD40L Antagonism in Rheumatoid Arthritis (RA) (NCT NCT05306353)

Two participants signed an informed consent form but screen failed during the screening process. No participants were randomized prior to trial termination.

CD40L Antagonism in Rheumatoid Arthritis (RA)

Defined by a Simplified Disease Activity Index (SDAI) \<= 11 Participants who escalate their disease-modifying therapy or take any prohibited medications for treatment of RA prior to Week 16 are considered to have failed the primary endpoint. The primary analysis will compare the primary endpoint between the two blinded study arms: VIB4920 with TNFi and VIB4920 placebo with TNFi study arms

Defined by Simplified Disease Activity Index (SDAI) \<= 3.3

Defined by Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) \<= 3.2

Defined by Simplified Disease Activity Index (SDAI) \<= 3.3. Participants who escalate their disease-modifying therapy or take prohibited medications for treatment of their RA prior to week 16 are considered to have failed this secondary endpoint

Defined by Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) \< 2.6. Participants who escalate their disease-modifying therapy or take prohibited medications for treatment of their Rheumatoid Arthritis (RA) prior to week 16 are considered to have failed this secondary endpoint

Defined by SDAI \<= 11; for participants who fail to achieve low disease activity or remission prior to escalating their disease-modifying therapy or taking a prohibited medication for treatment of RA, we will assume low disease activity and remission is not achievable.

Defined by Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) \<= 3.2; for participants who fail to achieve low disease activity or remission prior to escalating their disease-modifying therapy or taking a prohibited medication for treatment of RA, we will assume low disease activity and remission is not achievable.

Defined by Simplified Disease Activity Index (SDAI) \<= 3.3; for participants who fail to achieve low disease activity or remission prior to escalating their disease-modifying therapy or taking a prohibited medication for treatment of RA, we will assume low disease activity and remission is not achievable.

Defined by Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) \< 2.6; for participants who fail to achieve low disease activity or remission prior to escalating their disease-modifying therapy or taking a prohibited medication for treatment of RA, we will assume low disease activity and remission is not achievable.

Defined by Simplified Disease Activity Index (SDAI) \> 11 for the subset of individuals achieving low disease activity by the SDAI criteria. Participants who escalate their disease-modifying therapy or take prohibited medications for treatment of their RA will be considered to have lost the low disease activity or remission response

Defined by Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) \> 3.2 for the subset of individuals achieving low disease activity by the DAS28-CRP criteria. Participants who escalate their disease-modifying therapy or take prohibited medications for treatment of their RA will be considered to have lost the low disease activity or remission response

Defined by Simplified Disease Activity Index (SDAI) \> 3.3 for the subset of individuals achieving remission by the SDAI criteria. Participants who escalate their disease-modifying therapy or take prohibited medications for treatment of their RA will be considered to have lost the low disease activity or remission response

Defined by DAS28-CRP \>= 2.6 for the subset of individuals achieving remission by the DAS28-CRP criteria. Participants who escalate their disease-modifying therapy or take prohibited medications for treatment of their RA will be considered to have lost the low disease activity or remission response

Liver chemistry abnormalities will be graded using protocol specific criteria, defined relative to the upper limit of normal (ULN): * Aspartate aminotransferase \[AST\] increased: Grade 2: \> 3.0x ULN - 5.0x ULN, Grade 3: \> 5.0x ULN - 20.0x ULN, Grade 4: \> 20.0x ULN * Alanine aminotransferase \[ALT\] increased: Grade 2: \> 3.0x ULN - 5.0x ULN, Grade 3: \> 5.0x ULN - 20.0x ULN, Grade 4: \> 20.0x ULN * Alkaline phosphatase \[ALP\] increased: Grade 2: \> 2.5x ULN - 5.0x ULN, Grade 3: \> 5.0x ULN - 20.0x ULN, Grade 4: \> 20.0x ULN * Blood bilirubin increased: Grade 2: \> 1.5x ULN - 3.0x ULN, Grade 3: \> 3.0x ULN - 10.0x ULN, Grade 4: \> 10.0x ULN All other AEs will be graded according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

An adverse event or suspected adverse reaction is considered "serious" if, in the view of either the investigator or Sponsor (DAIT/NIAID), it results in any of the following outcomes (21 CFR 312.32(a)): 1. Death. 2. A life-threatening event: An AE or SAR is considered "life-threatening" if, in the view of either the investigator or Sponsor (DAIT/NIAID), its occurrence places the participant at immediate risk of death. It does not include an AE or SAR that, had it occurred in a more severe form, might have caused death. 3. Inpatient hospitalization or prolongation of existing hospitalization. 4. Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. 5. Congenital anomaly or birth defect.

The following are considered Adverse Events of Special Interest (AESI): * Anaphylaxis and grade 3 or higher hypersensitivity reactions * Grade 3 or higher infusion reactions * AST or ALT \>3xULN with serum total bilirubin \> 2xULN (Hy's Law) * Grade 3 or higher infection * Opportunistic infections including but not limited to reactivation of latent viral infections, invasive fungal infections, and TB * Malignant neoplasm * Immune complex disease