CD40L Antagonism in Rheumatoid Arthritis (RA)

NCT05306353 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: DAIT ITN092AI
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 5

Brief Summary

The primary objective is to determine if the addition of a 12-week course of treatment with VIB4920 to TNFi treatment will result in improved clinical disease control in patients with RA who have had an inadequate response to a TNFi.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; VIB4920; TNFi

Outcome Measures

Primary Outcomes (1)

• Proportion of participants achieving low disease activity by Simplified Disease Activity Index (SDAI)

  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

  Week 16

Secondary Outcomes (27)

• Proportion of participants who achieve sustained remission

  Week 16 to Week 40

• Proportion of participants achieving low disease activity by Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP)

  Week 16

• Proportion of participants achieving remission defined by SDAI

  Week 16

• Proportion of participants achieving remission defined by DAS28-CRP

  Week 16

• The proportion of participants achieving an ACR20 response

  Week 16

Study Arms (3)

VIB4920 Placebo with TNFi

PLACEBO COMPARATOR

Participants will receive VIB4920 placebo in a blinded fashion intravenously at weeks 0, 2, 4, 8, and 12 and continue all background disease-modifying RA therapy, including the TNFi, through the study period VIB4920 placebo consists of 0.9% normal saline in 250mL bags.

Drug: Placebo for VIB4920

VIB4920 with TNFi

EXPERIMENTAL

Participants will receive VIB4920 in a blinded fashion intravenously at a dose of 1500 mg at weeks 0, 2, 4, 8, and 12 and continue all background disease-modifying RA therapy, including the TNFi, through the study period

Drug: VIB4920 with TNFi

VIB4920 without TNFi

EXPERIMENTAL

Participants will stop TNFi after randomization to this arm, and receive VIB4920 in an evaluator-blinded fashion intravenously at a dose of 1500 mg at weeks 0, 2, 4, 8, and 12 while maintaining all other background disease-modifying RA therapy (e.g., methotrexate, hydroxychloroquine, etc.) through the study period. This arm is evaluator blinded (not aware of treatment status), with the participant aware of treatment status but evaluator is not, due to not using a TNFi placebo for this study

Drug: VIB4920 without TNFi

Interventions

Placebo for VIB4920 DRUG

26 participants will receive VIB4920 placebo administered intravenously at weeks 0, 2, 4, 8, and 12 while continuing background rheumatoid arthritis (RA) therapy including tumor necrosis factor alpha inhibitor (TNFi) (double-blinded)

VIB4920 Placebo with TNFi

VIB4920 with TNFi DRUG

52 participants will receive 1500 mg administered intravenously at weeks 0, 2, 4, 8, and 12 while continuing background rheumatoid arthritis (RA) therapy including Tumor necrosis factor alpha inhibitor (TNFi) (double blinded)

VIB4920 with TNFi

VIB4920 without TNFi DRUG

Participants will receive 1500 mg administered intravenously at weeks 0, 2, 4, 8, and 12 but discontinue necrosis factor alpha inhibitor (TNFi) while continuing all other background rheumatoid arthritis (RA) therapy (evaluator-blinded)

VIB4920 without TNFi

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant or legally authorized representative must be able to understand and provide informed consent
• Adults ≥ 18 years of age
• Diagnosed with RA by fulfilling the ACR/EULAR 2010 Classification Criteria for RA ≥ 6 months prior to screening (Appendix 9)
• Documented positive test for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibody (ACPA)
• SDAI ≥ 17
• At least 4 tender and 4 swollen joints by a 44 joint count (Appendix 5)
• Receiving treatment with an FDA-approved TNFi (including biosimilars) that is dosed subcutaneously at an FDA-approved dosing regimen for at least 12 weeks.
• Willing to continue or discontinue treatment with their current TNFi at the same dose depending upon study arm assignment
• If treated with leflunomide, sulfasalazine, or hydroxychloroquine, must be taking a stable dose for at least 12 weeks
• 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:
• Holding methotrexate after COVID-19 vaccination as per American College of Rheumatology guidance (https://rheumatology.org/)
• Holding methotrexate for 1 or 2 weeks after influenza vaccination
• 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

You may not qualify if:

• Inability or unwillingness to give written informed consent or comply with the study protocol
• 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
• Use of glucocorticoid and/or disease-modifying therapies as specified below:
• Prior treatment with any B cell depleting therapy (e.g., rituximab)
• Treatment with other biologic therapy (i.e., not targeting TNF-α), including abatacept, tocilizumab, or sarilumab within the previous 12 weeks
• Treatment with a JAK inhibitor within the previous 12 weeks
• Concurrent use of methotrexate and leflunomide in combination
• Prednisone \> 10 mg a day or equivalent glucocorticoid use within the previous 4 weeks
• Intramuscular, intra-articular, or intravenous glucocorticoids within the previous 4 weeks
• Other immunomodulatory medications within the previous 12 weeks except for methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine
• 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
• Use of an investigational agent including VIB4920 in the past 30 days or 5 half-lives, whichever is longer
• History of a severe allergy, hypersensitivity reaction, or infusion reaction to any component of the VIB4920 formulation
• History of Felty's syndrome
• History of interstitial lung disease with FVC \< 70% predicted, DLCO \< 70% predicted, or requiring supplemental oxygen

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Immune Tolerance Network (ITN): collaborator

Study Sites (5)

University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center

San Francisco, California, 94110, United States

Location

University of Colorado School of Medicine: Division of Rheumatology

Aurora, Colorado, 80045, United States

Location

Brigham & Women's Hospital: Department of Medicine, Rheumatology, Immunology

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology

Ann Arbor, Michigan, 48109, United States

Location

Duke University Medical Center: Division of Rheumatology and Immunology

Durham, North Carolina, 27710, United States

Location

Related Links

• Immune Tolerance Network (ITN)
• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Eugene William St. Clair

  Duke University Medical Center: Division of Rheumatology and Immunology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: April 1, 2022
• Study Start: July 25, 2023
• Primary Completion: July 28, 2025
• Study Completion: July 28, 2025
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial
• Access Criteria: Open access.

Locations

US (5)