Immunoglobulin A Nephropathy
Conditions
Interventions
Study Sites
• Sri Jayewardenepura General Hospital
• National Hospital of Sri Lanka
• National Hospital, Kandy
• Kurunegala Teaching Hospital
• Karapitiya Teaching Hospital
Randomization: Subjects w
2.0 g/g), screening estimated glomerular filtration rate (eGFR
30 - 44 mL/min versus >45 mL/min), and sodium-glucose cotransporter-2 inhibitor (SGLT2i) use at the time of randomization (yes or no).
Approximately 450 subjects will be randomized with equal allocat
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Eligibility
Inclusion criteria
Inclusion criteria: • Male and female patients >18 years of age. • Biopsy-confirmed IgA Nephropathy (IgAN). (Patients with an eGFR of 30 to 45 mL/min/1.73m2 must have had a kidney biopsy performed within 36 months of the screening visit). • Stable and maximally tolerated dose of ACEI (Angiotensin-converting enzyme inhibitor) and/or ARB (Angiotensin receptor blocker) for at least 3 months prior to screening. Patients who are on a stable dose of SGLT2i may participate if treatment was initiated >3 months prior to screening. Patients who are unable to take an ACEI or ARB may participate if their overall management conforms with standards of care and other protocol requirements. • Screening urine protein/creatinine ratio (uPCR) >0.75 g/g or urine protein >1.0 g/day • eGFR >30 mL/min/1.73 m2, (for the exploratory cohort* only: eGFR 20- <30 mL/min/1.73 m2), calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. *The Exploratory cohort is up to 20 subjects with IgAN and an eGFR of 20 to 30 mL/min/1.73 m2. These subjects will also randomized with equal allocation (1:1) to sibeprenlimab or placebo in this cohort.
Exclusion criteria
Exclusion criteria: • Secondary forms of IgAN or IgA vasculitis. • Coexisting chronic kidney disease other than IgAN. • Kidney biopsy findings in addition to IgAN including those of diabetic nephropathy, membranous nephropathy, or lupus nephritis. Hypertensive vascular changes are acceptable. • Kidney biopsy MEST (Mesangial cellularity, endocapillary proliferation, segmental sclerosis, tubular atrophy) or MEST-C (MEST-Crescents) score of T2 or C2 (Oxford IgAN classification). If MEST-scoring was not performed, the presence of > 50% tubulo-interstitial fibrosis, or crescents in > 25% of glomeruli is exclusionary. This does not apply to the exploratory cohort*. • Nephrotic syndrome • Serum IgG < 600 mg/dL at screening. • Chronic systemic immunosuppression, including glucocorticoids, within 16 weeks of randomization • Participation in another interventional clinical trial and receipt of another investigational drug within 30 days prior to the administration of IMP or 5 half-lives from last investigational drug administration, whichever is longer. • Chronic infectious disease, or acute infectious disease at time of screening. • Type 1 diabetes, or poorly controlled Type 2 diabetes • Uncontrolled hypertension *The Exploratory cohort is up to 20 subjects with IgAN and an eGFR of 20 to 30 mL/min/1.73 m2. These subjects will also randomized with equal allocation (1:1) to sibeprenlimab or placebo in this cohort.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Urinary protein to creatinine ratio (uPCR) in a 24-hour collection [At 9 months] | — |
Secondary
| Measure | Time frame |
|---|---|
| Annualized rate of change from baseline (slope) of eGFR. [[ Over 24 months] ] Proportion of subjects achieving urine total protein 25% reduction from baseline. [ [ At 12 months]] Annualized slope of eGFR. [[Over 12 months]] | — |
Countries
Argentina,Australia,Brazil,Canada,China,Czech Republic,France,Germany,Hong Kong,India,Israel,Italy,Japan,Korea, Republic of,Malaysia,Netherlands,Philippines,Poland,Portugal,Singapore,Spain,Sri Lanka,T
Contacts
Public ContactDr. Chula Herath
Consultant Nephrologist
Outcome results
None listed