Immunoglobulin A(IgA) Nephropathy
Conditions
Interventions
VIS649 or placebo will be administered as a single, monthly IV infusion for 12 monthly doses.
Sponsors
Nishioka Tsuyoshi
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant is a male or female >= 18 years of age at the time of signing the informed consent. 2. Participant has biopsy-confirmed IgAN. 3. Participant has medical records showing they have been on stable and maximally tolerated doses of either ACEI or ARB, as per local SOC and applicable guidelines, for at least 3 months preceding screening. Participants should optimally be on at least 50% of the maximum recommended dose of these agents; however, if a participant is on their maximally tolerated dose (and this is = 0.75 g/g measured from a 24-hour urine (or an intended 24 hour urine sample) or 24-hour urine protein >= 1.0 g/d, as measured from 24 hour urine collection (or an intended 24 hour urine sample). - The proteinuria should be assessed when the participant is considered to be in a steady state with no recent heavy exercise, fever, or other potential issues that could impact the result. Re-testing may be allowed if it is determined that the participant was not in steady state after consultation with the medical monitor. 5. Participant has eGFR >= 45 mL/min/1.73 m2, calculated using the CKD-EPI formula. - Retesting may be allowed if it is determined that the participant was not in steady state after consultation with the medical monitor. - Participants with eGFR >= 30 mL/min/1.73 m2 and = 50% tubulo-interstitial fibrosis (T2 if using MEST-C score) or crescents in > 25% of glomeruli (C2 if using MEST-C score).The eGFR should be measured when the participant is considered to be in a steady state without recent changes in volume status, medications that could impact the result (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], aminoglycosides, co-trimoxazole), or changes in dietary protein intake. 6. Participants serum Ig values must meet the following criteria: - IgG: >= 700 mg/dL - IgM: >= 37 mg/dL - IgA: >= 70 mg/dL 7. Female participants of childbearing potential must have a negative serum pregnancy test prior to the first dose. 8. Participant is willing to adhere to contraceptive requirements. 9. Participant or a legally authorized representative is able to understand the purpose and risks of the study and is willing to give voluntary written informed consent as described.
Exclusion criteria
Exclusion criteria: 1. Participant has secondary forms of IgAN as defined by the treating physician (eg, Henoch Schonlein purpura (IgA vasculitis), infection-associated IgAN, or IgAN associated with hepatic cirrhosis). 2. Participant has co-existing CKD, other than IgAN. 3. Participant has evidence of additional pathological findings in the kidney biopsy (eg, diabetic kidney disease, membranous nephropathy, or lupus nephritis). However, hypertensive vascular changes are acceptable. 4. Participant has kidney biopsy MEST or MEST-C score of T2 or C2 from the Oxford IgAN classification schema. If MEST-scoring was not performed, the presence of > 50% tubulo interstitial fibrosis or crescents in > 25% of glomeruli is exclusionary. 5. Participant has nephrotic syndrome, defined for this purpose as 24-hour urine protein > 3.5 g with concurrent hypoalbuminemia (serum albumin 350 mg/dL), and edema. Participants with isolated nephrotic range proteinuria (>3.5 g/d) will be eligible. 6. Participant has received a solid organ transplant, including kidney. 7. Participant has received bone marrow or hematologic stem cell transplantation. 8. Participant is currently receiving systemic immunosuppression (excluding topical, ophthalmic, per rectum, or inhaled corticosteroids). 9. Participant has received treatment with systemic corticosteroid therapy (excluding topical, ophthalmic, per rectum, or inhaled corticosteroids) within 16 weeks of initial screening. 10. Participant has received treatment with a systemic immunosuppressive agent (e.g., mycophenolate mofetil, azathioprine, calcineurin inhibitors, cyclophosphamide/cytotoxic agents) within 16 weeks of initial screening. 11. Participant has any chronic infectious disease (eg, chronic urinary tract infection; chronic sinusitis; bronchiectasis; active pulmonary or systemic tuberculosis; chronic viral hepatitis, such as hepatitis C or hepatitis B; or human immunodeficiency virus infection). See Section 4.1 Study Design for further details. 12. Participant has acute infectious disease at the time of screening. Participants may be rescreened following resolution of acute infection (such as urinary tract infection or respiratory tract infection), provided there is no evidence of an immunosuppressive condition that predisposed the participant to this infection. 13. Participant has Type 1 diabetes. 14. Participant has uncontrolled Type 2 diabetes, as evidenced by a screening hemoglobin A1c value > 8%. 15. Participant has uncontrolled BP (> 140 mm Hg systolic or > 90 mm Hg diastolic), Systolic and diastolic BP should be assessed while the participant is seated or supine for at least 5 minutes in a quiet room without distractions. BP should be measured with a completely automated device. At least 3 readings should be taken and average values from these 3 readings should be calculated. 16. Participant has a history of chronic autoimmune neurodegenerative disorder such as multiple sclerosis. 17. Participant has a known allergy or intolerance to any component of the study intervention. 18. Participant is breastfeeding. 19. Participant has poorly compensated or controlled ischemic heart disease or cardiomyopathy, as judged by the Investigator. 20. Participant has chronic obstructive pulmonary disease (COPD) or asthma that has required systemic steroid therapy during the prior year. If COPD is present, severity must not exceed Global Initiative for Chronic Obstructive Lung Disease 1 (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety: - AEs graded by severity, clinical laboratory tests, vital sign measurements, and physical examinations Efficacy: - Change from baseline in uPCR (measured on natural log scale from 24-hour urine collection or the intended 24-hour urine collection) at Month 12 (ie, approximately 30 days after the 12th dose is administered) | — |
Countries
Australia, Canada, Hong Kong, India, Japan, Malaysia, Philippines, Singapore, South Korea, Spain, Sri Lanka, Taiwan, Thailand, The United States, United Kingdom
Contacts
Public ContactTsuyoshi Nishioka
Fortrea Japan K.K.
Outcome results
None listed