Summary

Eligibility
for people ages 18-70 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion

Description

Summary

Patients with moderately-to-highly active Rheumatoid arthritis receive a 12-week VIB4920 treatment with Tumor necrosis factor alpha inhibitor (TNFi) compared to background disease-modifying (RA) therapy with TNFi and without the addition of VIB4920. The primary objective is to determine if the addition of a 12-week course of treatment with VIB4920 to a TNFi in patients with RA who have had an inadequate response to a TNFi results in improved clinical disease control.

Official Title

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

Details

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 (etanercept or adalimumab) for at least 12 weeks. Study participation is divided into two phases: the study drug administration period (from week 0 to week 12) and the post-administration observation period (from week 12 to week 40). Participants will be randomized into one of the following three study arms to assess the efficacy of adding VIB4920 to background disease modifying RA therapy including TNFi and replacing TNFi with VIB4920, as well as the safety of this combination of biologic agents compared to either agent alone.

Keywords

Rheumatoid Arthritis VIB4920 TNFi Arthritis Arthritis, Rheumatoid VIB4920 with TNFi VIB4920 without TNFi

Eligibility

You can join if…

Open to people ages 18-70

  1. Participant or legally authorized representative must be able to understand and provide informed consent
  2. Adult 18-70 years of age
  3. Diagnosed with RA by fulfilling the ACR/EULAR 2010 Classification Criteria for Rheumatoid Arthritis (RA) >= 6 months prior to screening
  4. Documented positive test for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibody (ACPA)
  5. Simplified Disease Activity Index (SDAI) >= 17
  6. At least 4 tender and 4 swollen joints by a 44 joint count
  7. Tumor necrosis factor alpha inhibitor (TNFi) therapy:
  8. Current treatment with etanercept 50 mg SC weekly or adalimumab 40 mg SC every other week for at least 12 weeks
  9. Willing to continue or discontinue treatment with their current TNFi at the same dose depending upon study arm assignment
  10. If treated with leflunomide, sulfasalazine, or hydroxychloroquine, must be taking a stable dose for at least 12 weeks
  11. 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:
  12. Holding methotrexate for 1 week after each dose of a 2 dose SARS-CoV-2 vaccine
  13. Holding methotrexate for 2 weeks after a single dose SARS-CoV-2 vaccine
  14. Holding methotrexate for 1 or 2 weeks after influenza vaccination
  15. . Received at least 3 doses of any combination of the Moderna or Pfizer COVID-19 vaccine, or 1 dose of the Janssen COVID-19 vaccine followed by a dose of either the Pfizer or Moderna COVID-19 vaccine, unless the participant had a significant adverse reaction to COVID-19 vaccination. Participants who have had a significant adverse reaction to COVID-19 vaccination must have received at a minimum 2 doses of any combination of the Moderna or Pfizer COVID-19 vaccine, or 1 dose of the Janssen COVID-19 vaccine followed by a dose of either the Pfizer or Moderna COVID-19 vaccine. The last COVID-19 vaccine dose must have been administered at least 14 days prior to the initiation of study drug (Visit 0).
  16. . All participants who engage in sexual activity that could lead to pregnancy must agree to use abstinence or an US Food and Drug Administration (FDA) approved contraception for the duration of the study to prevent pregnancy

You CAN'T join if...

  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 Rheumatoid Arthritis (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:
  4. Prior treatment with any B cell depleting therapy (e.g., rituximab)
  5. History of treatment with more than two Tumor necrosis factor alpha inhibitors (TNFi), including ongoing treatment with etanercept or adalimumab
  6. Treatment with other biologic therapy (i.e., not targeting TNF-alfa), including abatacept, tocilizumab, or sarilumab within the previous 12 weeks
  7. Treatment with a Janus kinase (JAK) inhibitor within the previous 12 weeks
  8. Concurrent use of methotrexate and leflunomide
  9. Prednisone > 10 mg a day or equivalent glucocorticoid use within the previous 4 weeks
  10. Intramuscular, intra-articular, or intravenous glucocorticoids within the previous 4 weeks
  11. Other immunomodulatory medications within the previous 12 weeks except for methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine
  12. Lack of any subjective or objective clinical response (i.e., complete non-responder) to current TNFi use, in the opinion of the study investigator based on information provided by the patient and referring rheumatologist
  13. Use of an investigational agent including VIB4920 in the past 30 days or 5 half-lives, whichever is longer
  14. History of a severe allergy, hypersensitivity reaction, or infusion reaction to any component of the VIB4920 formulation
  15. History of Felty's syndrome
  16. History of interstitial lung disease with FVC < 70% predicted, DLCO < 70% predicted, or requiring supplemental oxygen
  17. Hypercoagulable state as specified below:
  18. Previous deep venous or arterial thrombosis or thromboembolism, or pulmonary embolism
  19. Known hypercoagulable state (e.g., inherited thrombin III deficiency, protein S deficiency, protein C deficiency, antiphospholipid antibody syndrome, MTHFR mutation)
  20. Risk factors for deep venous or arterial thromboembolism (e.g., immobilization or major surgery within 12 weeks prior to enrollment)
  21. Anti-phospholipid antibodies:
  22. Positive anti-cardiolipin IgG, IgM, or IgA antibodies at a moderate titer or higher (>= 40 U) ii. Positive anti-beta-2-glycoprotein I IgG, IgM, or antibodies at a moderate titer or higher (>= 40 U) iii. Positive lupus anticoagulant test
  23. . Infection:
  24. 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)
  25. Positive Hepatitis C Virus (HCV) serology unless treated with an anti-viral regimen resulting in a sustained virologic response (undetectable viral load 24 weeks after cessation of therapy)
  26. Evidence of Human Immunodeficiency Virus (HIV) infection
  27. Evidence of active tuberculosis, untreated or incompletely treated latent tuberculosis, or recent close contact with a person who has active tuberculosis
  28. Positive QuantiFERON-TB Gold or QuantiFERON-TB Gold Plus test without history of previous treatment for latent TB
  29. Indeterminate QuantiFERON-TB Gold or QuantiFERON-TB Gold Plus test which remains indeterminate on repeat testing, and any of the following:
  30. History of tuberculosis exposure ii. History of travel to an area where tuberculosis is endemic iii. Findings on chest radiograph obtained in the past 3 months suggestive of prior exposure to tuberculosis (e.g., granulomas or apical scarring) iv. Positive purified protein derivative (PPD) skin test for tuberculosis obtained in 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 tuberculosis (TB)
  31. Positive test for acute COVID-19 infection (e.g., PCR test for SARS-CoV-2 or alternative viral test according to CDC guidance)
  32. Symptoms of presumed or documented COVID-19 infection in the past 30 days
  33. More than one episode of herpes zoster in the past 12 months
  34. An opportunistic infection in the past 12 months
  35. 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
  36. History of bronchiectasis with recurrent pulmonary infections
  37. . History of a primary immunodeficiency disorder
  38. . Vaccination with a live vaccine within the past 30 days
  39. . Women who are pregnant or breast-feeding
  40. . White Blood Cell (WBC) count < 3.0 x 103/mcl

  41. . Absolute neutrophil count < 1.5 x 103/mcl

  42. . Hemoglobin < 9 g/dL
  43. . Platelet count < 100 x 103/mcl

  44. . Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥=2x the upper limit of normal (ULN)
  45. . 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
  46. . 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
  47. . 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)
  48. . 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
  49. . Inability to comply with study and follow-up procedures

Locations

  • 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

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Links
Immune Tolerance Network (ITN) National Institute of Allergy and Infectious Diseases (NIAID) Division of Allergy, Immunology, and Transplantation (DAIT)
ID
NCT05306353
Phase
Phase 2 research study
Study Type
Interventional
Last Updated