Rheumatoid ArthritisPhase 2CONTROL-RANCT05306353
CD40L Antagonism in Rheumatoid Arthritis (RA)
A Phase 2 study testing VIB4920 with TNFi and VIB4920 without TNFi in people with Rheumatoid Arthritis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- VIB4920 with TNFi and VIB4920 without TNFi
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 5 sitesUnited States
- Study dates
- 25 Jul 2023to 28 Jul 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
- Arterial or deep venous thromboembolism including pulmonary embolism in the prior two years
- Infection:
- 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
- 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
- History of a primary immunodeficiency disorder
- Vaccination with a live vaccine within the past 30 days
- Women who are pregnant or breast-feeding
- White Blood Cell (WBC) count < 3.0 x 103/μl
- Absolute neutrophil count < 1.5 x 103/μl
- Hemoglobin < 9 g/dL
- Platelet count < 100 x 103/μl
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2x the upper limit of normal (ULN)
- 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
- 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
- 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)
- 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
- Inability to comply with study and follow-up procedures
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology
Ann Arbor, Michigan, 48109
University of Colorado School of Medicine: Division of Rheumatology
Aurora, Colorado, 80045
Brigham & Women's Hospital: Department of Medicine, Rheumatology, Immunology
Boston, Massachusetts, 02215
Duke University Medical Center: Division of Rheumatology and Immunology
Durham, North Carolina, 27710
University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center
San Francisco, California, 94110
About this study
Official title: Combining a CD40L-Binding Protein (VIB4920) With a TNF-alpha Inhibitor for the Treatment of Inadequately Controlled Rheumatoid Arthritis (ITN092AI)
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.
Read the detailed description
This study is a phase 2, multi-site, prospective, randomized, placebo-controlled, three-arm [two arms double-blinded, one arm evaluator-blinded (participant is aware of his/her treatment status, but evaluator is not)] trial of VIB4920 in 104 adults with seropositive Rheumatoid arthritis (RA) in the United States. Individuals will be eligible if they have moderate or high disease activity (Simplified Disease Activity Index [SDAI] ≥ 17) despite treatment with a TNFi for at least 12 weeks. All FDA-approved TNFi (including biosimilars) administered subcutaneously utilizing FDA-approved dosing regimens are permitted.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Placebo for VIB4920, VIB4920 with TNFi, VIB4920 without TNFi
- Keywords
- Rheumatoid arthritis, VIB4920, TNFi
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo for VIB4920Drug
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 with TNFiDrug
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 without TNFiDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: 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 Receives: Drug: VIB4920 without TNFi |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Week 16
Secondary outcomes (27)
Proportion of Participants Who Achieve Sustained Remission
Defined by Simplified Disease Activity Index (SDAI) <= 3.3
Measured: Week 16 to Week 40
Proportion of Participants Achieving Low Disease Activity by Disease Activity Score-28 for Rheumatoid Arthritis With CRP (DAS28-CRP)
Defined by Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) <= 3.2
Measured: Week 16
Proportion of Participants Achieving Remission Defined by SDAI
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
Measured: Week 16
Proportion of Participants Achieving Remission Defined by DAS28-CRP
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
Measured: Week 16
The Proportion of Participants Achieving an ACR20 Response
Measured: Week 16
The Proportion of Participants Achieving an ACR50 Response
Measured: Week 16
The Proportion of Participants Achieving an ACR70 Response
Measured: Week 16
The Proportion of Participants Achieving an ACR20 Response
Measured: Week 40
The Proportion of Participants Achieving an ACR50 Response
Measured: Week 40
The Proportion of Participants Achieving an ACR 70 Response
Measured: Week 40
Time to First Occurrence of Low Disease Activity as Defined by SDAI
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.
Measured: Week 0 to Week 40
Time to First Occurrence of Low Disease Activity as Defined by DAS28-CRP
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.
Measured: Week 0 to Week 40
Time to First Occurrence of Remission as Defined by SDAI
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.
Measured: Week 0 to Week 40
Time to First Occurrence of Remission as Defined by DAS28-CRP
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.
Measured: Week 0 to Week 40
Time to Loss of Low Disease Activity Defined by SDAI
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
Measured: Week 16
Time to Loss of Low Disease Activity Defined by DAS28-CRP
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
Measured: Week 16
Time to Loss of Remission Defined by SDAI
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
Measured: Week 16
Time to Loss of Remission Defined by DAS28-CRP
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
Measured: Week 16
Longitudinal Trends in Simplified Disease Activity Index (SDAI)
Measured: Week 0 to Week 40
Longitudinal Trends in Disease Activity Score-28 for Rheumatoid Arthritis With CRP (DAS28-CRP)
Measured: Week 0 to Week 40
Change in the Health Assessment Questionnaire - Disability Index (HAQ-DI)
Measured: Week 0 to 16
Change in the Health Assessment Questionnaire - Disability Index (HAQ-DI)
Measured: Week 0 to 40
Change in Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Profile Scores
Measured: Week 0 to Week 40
Change in Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Profile Scores
Measured: Week 0 to 16
Incidence of Grade 2 or Higher Adverse Events (AEs)
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.
Measured: Week 0 to Week 40
Incidence of Serious Adverse Events
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)):
- Death.
- 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.
- Inpatient hospitalization or prolongation of existing hospitalization.
- Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions.
- Congenital anomaly or birth defect.
Measured: Week 0 to Week 40
Incidence of Adverse Events of Special Interest (AESI)
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
Measured: Week 0 to Week 40
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2022
- Study start25 Jul 2023
- Primary completion28 Jul 2025
- Study completion28 Jul 2025
Why it stopped: The study is being closed early due to insufficient participant enrollment across study sites.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Responsible party
- Sponsor
- Investigators
- Eugene William St. Clair, Study chair, Duke University Medical Center: Division of Rheumatology and Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05306353
- Sponsor's protocol ID
- DAIT ITN092AI
- Acronym
- CONTROL-RA
- Status last verified
- Jun 2026
- First submitted
- 23 Mar 2022
- Last updated
- 20 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The plan is to share data upon completion of the study in Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining a CD40L-Binding Protein (VIB4920) With a TNF-alpha Inhibitor for the Treatment of Inadequately Controlled Rheumatoid Arthritis (ITN092AI)
- ClinicalTrials.gov ID
- NCT05306353
- Acronym / sponsor ID
- CONTROL-RA / DAIT ITN092AI
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid arthritis, VIB4920, TNFi
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study is being closed early due to insufficient participant enrollment across study sites.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Study start
- 25 Jul 2023 (actual)
- Primary completion
- 28 Jul 2025 (actual)
- Study completion
- 28 Jul 2025 (actual)
- First posted
- 1 Apr 2022 (actual)
- Results
- Posted 20 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study is a phase 2, multi-site, prospective, randomized, placebo-controlled, three-arm [two arms double-blinded, one arm evaluator-blinded (participant is aware of his/her treatment status, but evaluator is not)] trial of VIB4920 in 104 adults with seropositive Rheumatoid arthritis (RA) in the United States. Individuals will be eligible if they have moderate or high disease activity (Simplified Disease Activity Index [SDAI] ≥ 17) despite treatment with a TNFi for at least 12 weeks. All FDA-approved TNFi (including biosimilars) administered subcutaneously utilizing FDA-approved dosing regimens are permitted.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| VIB4920 Placebo with TNFi | Placebo comparator | Drug: Placebo for VIB4920Participants 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. |
| VIB4920 with TNFi | Experimental | Drug: VIB4920 with TNFiParticipants 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 |
| VIB4920 without TNFi | Experimental | Drug: VIB4920 without TNFiParticipants 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (32 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo for VIB492026 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) | Drug | VIB4920 Placebo with TNFi |
| VIB4920 with TNFi52 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) | Drug | VIB4920 with TNFi |
| VIB4920 without TNFiParticipants 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) | Drug | VIB4920 without TNFi |
Primary outcome
Proportion of Participants Achieving Low Disease Activity by Simplified Disease Activity Index (SDAI)
Time frame: Week 16
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
27 secondary outcomes
Proportion of Participants Who Achieve Sustained Remission
Time frame: Week 16 to Week 40
Proportion of Participants Achieving Low Disease Activity by Disease Activity Score-28 for Rheumatoid Arthritis With CRP (DAS28-CRP)
Time frame: Week 16
Proportion of Participants Achieving Remission Defined by SDAI
Time frame: Week 16
Proportion of Participants Achieving Remission Defined by DAS28-CRP
Time frame: Week 16
The Proportion of Participants Achieving an ACR20 Response
Time frame: Week 16
The Proportion of Participants Achieving an ACR50 Response
Time frame: Week 16
The Proportion of Participants Achieving an ACR70 Response
Time frame: Week 16
The Proportion of Participants Achieving an ACR20 Response
Time frame: Week 40
The Proportion of Participants Achieving an ACR50 Response
Time frame: Week 40
The Proportion of Participants Achieving an ACR 70 Response
Time frame: Week 40
Time to First Occurrence of Low Disease Activity as Defined by SDAI
Time frame: Week 0 to Week 40
Time to First Occurrence of Low Disease Activity as Defined by DAS28-CRP
Time frame: Week 0 to Week 40
Time to First Occurrence of Remission as Defined by SDAI
Time frame: Week 0 to Week 40
Time to First Occurrence of Remission as Defined by DAS28-CRP
Time frame: Week 0 to Week 40
Time to Loss of Low Disease Activity Defined by SDAI
Time frame: Week 16
Time to Loss of Low Disease Activity Defined by DAS28-CRP
Time frame: Week 16
Time to Loss of Remission Defined by SDAI
Time frame: Week 16
Time to Loss of Remission Defined by DAS28-CRP
Time frame: Week 16
Longitudinal Trends in Simplified Disease Activity Index (SDAI)
Time frame: Week 0 to Week 40
Longitudinal Trends in Disease Activity Score-28 for Rheumatoid Arthritis With CRP (DAS28-CRP)
Time frame: Week 0 to Week 40
Change in the Health Assessment Questionnaire - Disability Index (HAQ-DI)
Time frame: Week 0 to 16
Change in the Health Assessment Questionnaire - Disability Index (HAQ-DI)
Time frame: Week 0 to 40
Change in Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Profile Scores
Time frame: Week 0 to Week 40
Change in Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Profile Scores
Time frame: Week 0 to 16
Incidence of Grade 2 or Higher Adverse Events (AEs)
Time frame: Week 0 to Week 40
Incidence of Serious Adverse Events
Time frame: Week 0 to Week 40
Incidence of Adverse Events of Special Interest (AESI)
Time frame: Week 0 to Week 40
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Immune Tolerance Network (ITN)Link provided by the sponsor.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
- Division of Allergy, Immunology, and Transplantation (DAIT)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. The plan is to share data upon completion of the study in Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eugene William St. Clair study chair
Duke University Medical Center: Division of Rheumatology and Immunology
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VIB4920 with TNFi and VIB4920 without TNFi in people with Rheumatoid Arthritis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Achieving Low Disease Activity by Simplified Disease Activity Index (SDAI) (time frame: Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2026.