TERMINATED

CD40L Antagonism in Rheumatoid Arthritis (RA)

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Combining a CD40L-Binding Protein (VIB4920) With a TNF-alpha Inhibitor for the Treatment of Inadequately Controlled Rheumatoid Arthritis (ITN092AI)

Quick Facts

Study Start:2023-07-25

Study Completion:2025-07-28

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:TERMINATED

Study ID

NCT05306353

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Participant or legally authorized representative must be able to understand and provide informed consent 2. Adults ≥ 18 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	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. Treatment with other biologic therapy (i.e., not targeting TNF-α), including abatacept, tocilizumab, or sarilumab within the previous 12 weeks 3. Treatment with a JAK inhibitor within the previous 12 weeks 4. Concurrent use of methotrexate and leflunomide in combination 5. Prednisone \> 10 mg a day or equivalent glucocorticoid use within the previous 4 weeks 6. Intramuscular, intra-articular, or intravenous glucocorticoids within the previous 4 weeks 7. 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: 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

Inclusion Criteria

Exclusion Criteria

1. Participant or legally authorized representative must be able to understand and provide informed consent
2. Adults ≥ 18 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

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. Treatment with other biologic therapy (i.e., not targeting TNF-α), including abatacept, tocilizumab, or sarilumab within the previous 12 weeks
3. Treatment with a JAK inhibitor within the previous 12 weeks
4. Concurrent use of methotrexate and leflunomide in combination
5. Prednisone \> 10 mg a day or equivalent glucocorticoid use within the previous 4 weeks
6. Intramuscular, intra-articular, or intravenous glucocorticoids within the previous 4 weeks
7. 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:
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

Contacts and Locations

Principal Investigator

Eugene William St. Clair

STUDY_CHAIR

Duke University Medical Center: Division of Rheumatology and Immunology

Study Locations (Sites)

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

San Francisco, California, 94110

United States

University of Colorado School of Medicine: Division of Rheumatology

Aurora, Colorado, 80045

United States

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

Boston, Massachusetts, 02215

United States

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

Ann Arbor, Michigan, 48109

United States

Duke University Medical Center: Division of Rheumatology and Immunology

Durham, North Carolina, 27710

United States

Collaborators and Investigators

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Eugene William St. Clair, STUDY_CHAIR, Duke University Medical Center: Division of Rheumatology and Immunology

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-07-25

Study Completion Date2025-07-28

Study Record Updates

Study Start Date2023-07-25

Study Completion Date2025-07-28

Terms related to this study

Keywords Provided by Researchers

Rheumatoid arthritis
VIB4920
TNFi

Additional Relevant MeSH Terms

Rheumatoid Arthritis