Immunoglobulin A Nephropathy
Conditions
Keywords
IgAN, Sibeprenlimab, VIS649
Brief summary
To Evaluate the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Subjects with Primary Immunoglobulin A Nephropathy
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sibeprenlimab 400 mg administered SC Q 4 weeks compared to placebo in patients with IgAN. The primary objective is to compare the relative change from baseline in the urinary protein to creatinine ratio (uPCR) in 24-hour urine collections, after 9 months of treatment. The key secondary objective is to compare the annualized rate of change from baseline (slope) of estimated glomerular filtration rate (eGFR) after approximately 24 months of treatment. There will be one main cohort comprised of approximately 450 subjects with source-verified biopsy-confirmed IgAN and eGFR ≥ 30 mL/min/1.73 m\^2. An additional exploratory cohort will be comprised of up to 20 subjects with source-verified biopsy confirmed IgAN and eGFR of 20 to \< 29 mL/min/1.73 m\^2.
Interventions
DRUGSibeprenlimab 400 mg
Solution for Injection
DRUGPlacebo
Placebo s.c. q 4 weeks
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female patients ≥ 18 years of age . * Biopsy-confirmed 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 and/or ARB 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 2021 CKD-EPI equation
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 or MEST-C 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 protocol provides additional information about these and other inclusion and
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 (slope) of eGFR | Over 24 months |
| Mean change of eGFR from baseline | Over 24 months |
| Progression to composite kidney failure (CKF) | Time from the randomization date to first occurrence of CKF |
| Percentage of participants with Progression to CKF | Over 24 months |
| Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations | Up to Week 112 |
| Number of Participants With Adverse Events (AEs) | Up to Week 112 |
| Number of Participants With Potentially Clinically Significant Changes in Laboratory Tests | Up to Week 112 |
| Number of Participants With Potentially Clinically Significant Changes in Vital Signs | Up to Week 112 |
| Number of Participants With Potentially Clinically Significant Changes in Physical Examinations | Up to Week 112 |
| Number of Participants With Injection Site Reactions | Up to Week 112 |
| Evaluation of serum ADA | Up to Week 112 |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Croatia, Czechia, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, Malaysia, Netherlands, Philippines, Poland, Portugal, Singapore, South Korea, Spain, Sri Lanka, Taiwan, Thailand, United Kingdom, United States, Vietnam
Outcome results
None listed