A Phase 2a Randomized Placebo-Controlled Double-Blind Multicenter Trial of VIB4920 for Active Lupus Nephritis

Summary of Study Intervention:

The purpose of this study is to evaluate the efficacy of VIB4920 (also named dazodalibep) in achieving a complete renal response in active Lupus Nephritis. Dazodalibep is a fusion protein that targets CD40 ligand (CD40L), a protein in your immune system that affects T cell and B cell activity. Previous studies have shown that blocking CD40L is efficacious in treatment of inflammatory and autoimmune conditions. The results of early clinical studies have shown support for the use of dazodalibep for treatment of autoimmune diseases such as rheumatoid arthritis and Sjogren’s Disease. 

Study participation is voluntary. Approximately 74 patients will be enrolled into this study worldwide, and approximately 2 patients will be from HSS. Study participants who meet the study’s eligibility requirements and are enrolled will be randomized to receive either dazodalibep or placebo in a ratio of 2:1. Treatment will be administered approximately every month via intravenous infusion, with the last dose at Week 24. The total study duration is 60 weeks. Visits should be completed per study schedule until the end of the study. The research staff will provide a schedule of assessments that illustrates when study subjects will be expected to attend study visits.

Inclusion Criteria:

Someone can participate in this study if they meet ALL of the following:

• • Age 18 years or older.
  • Classification of Systemic Lupus Erythematosus (SLE) by any of the following criteria: the 1997 update of the 1982 American College of Rheumatology (ACR) criteria, the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria, or the 2019 European League Against Rheumatism (EULAR)/ACR criteria.
  • UPCR ≥ 1.0 based on a 24-hour urine collection at screening or within 14 days prior to screening
  • Renal biopsy within 24 weeks prior to screening with both of the following:
    • • Class III, Class IV, or Class V in combination with Class III or IV, and
      • Modified NIH Activity Index ≥ 1.

Exclusion Criteria:

Someone cannot participate in this study if they have ANY of the following:

• • Contraindication to treatment with MMF or mycophenolate sodium.
  • Treatment with a biologic agent, except belimumab (Benlysta), or investigational agent within 90 days or 5 half-lives prior to first infusion, whichever is longer.
  • Rituximab or other B cell depleting agent within 6 months prior to the first infusion.
  • Receipt of a live attenuated vaccine within 4 weeks prior to the first infusion.
  • Comorbidities requiring treatment with systemic corticosteroids (i.e. asthma), including those that have required 3 or more courses of systemic corticosteroids within 12 months prior to the first infusion.
  • Current malignancy or history of malignancy, except for adequately treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma in situ > 12 months prior to the first infusion.
  • End Stage Renal Disease (ESRD), defined as estimated Glomerular Filtration Rate (eGFR) < 20 ml/min/1.73m2.
  • History of transplantation.
  • The following risks for thromboembolic events:
    • • Recent or recurrent deep venous thrombosis or arterial thromboembolism.
      • Immobilization or major surgery within 12 weeks prior to the first infusion.
      • History of congenital or inherited deficiency of antithrombin III, protein S, or protein C.
      • History of anti-phospholipid syndrome, according to the 2006 Sapporo classification criteria
  • Any one of the following laboratory abnormalities: (a). Peripheral B cell count < 5/μl; (b). Neutropenia (absolute neutrophil count < 1000/mm3); (c). Anemia (hemoglobin < 8 g/dL); (d). Thrombocytopenia (platelets < 50,000/mm3); (e). Aspartate aminotransferase or alanine aminotransferase ≥ 2x upper limit of normal.
  • Evidence of current or prior tuberculosis infection .
  • Human immunodeficiency virus (HIV) infection.
  • Current or past hepatitis B (HBV) infection, or hepatitis C virus (HCV) infection, except adequately treated HCV with documented sustained virologic response.
  • Active bacterial, viral, fungal, or opportunistic infection.
  • History of significant, recurrent, or chronic infection that may pose additional risks from participating in the study.
  • History of severe psychiatric condition that would interfere with the participant’s ability to comply with the study protocol.
  • Current substance abuse, or history of substance abuse within 12 months of the first infusion.
  • Lack of peripheral venous access.
  • Pregnant or breastfeeding.
  • Unwillingness to use a medically acceptable form of contraception for the duration of the study if female of child-bearing potential or if male with a partner of child-bearing potential.

Contact Information for the Study:

Natasha Zarrin

zarrinn@hss.edu

212.774.2967