A Study of BION-1301 in Adults With IgA Nephropathy

Study Overview
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Brief Summary
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Safety and Efficacy of BION-1301 in Adults with IgA Nephropathy

Detailed Description
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Approximately 272 patients with eGFR ≥ 30 mL/min/1.73m2 and with biopsy-proven IgAN will be randomized to receive 600mg Q2W BION-1301 or a matched placebo for 104 weeks. An additional exploratory cohort, not included in the primary analysis, will be comprised of approximately 20 subjects (10 subjects per arm) with biopsy-confirmed IgAN and eGFR of ≥ 20 to < 30 mL/min/1.73 m2. The primary objective of the study is to evaluate the effect of BION-1301 versus placebo on proteinuria in adults with IgA nephropathy. Subjects will have assessments of safety and efficacy for 2.5 years (up to 134 weeks). To facilitate study participation over this time period, where allowed by local regulations, options for remote study visits using telemedicine and home health may be offered.

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled Study of BION-1301 in Adults With IgA Nephropathy (The BEYOND Study)

Conditions
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IgA Nephropathy, Immunoglobulin A Nephropathy

Intervention / Treatment
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* Drug: BION-1301
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects aged ≥ 18 years at the time of signing the informed consent form (ICF) prior to initiation of any study specific activities/procedures. Biopsy-proven IgAN within the past 10 years that is not due to secondary causes. A pseudonymized copy of the report must be available for review. If biopsy report within 10 years is not available, re-biopsy may be permitted upon discussion with the Medical Monitor. eGFR ≥ 30 mL/min/1.73m2 at Screening based on the 2021 CKD-EPI equation (for the exploratory cohort only: eGFR of ≥20 to < 30 mL/min/1.73 m2). Total urine protein ≥ 1.0 g/day and UPCR ≥ 0.7 g/g, as measured from an adequate 24hour urine collection at Screening by a central laboratory. Stable on a maximally tolerated dose of ACEi/ARB for at least 12 weeks prior to Screening or intolerant to ACEi/ARB; may also be on a stable and well tolerated dose of SGLT2i and/or ERAs/MRAs for at least 12 weeks prior to Screening for the treatment of IgAN. Body mass index (BMI) between 18 and 40 kg/m2. Screening weight of at least 50 kg. Men and women of childbearing potential must agree to follow protocol-specified contraception guidance from Screening through approximately 5 half-lives after the final dose of study drug. Provide written informed consent and be willing to comply with study visits and procedures. Exclusion Criteria: Secondary forms of IgAN as determined by the Investigator, in the setting of systemic disorders, infections, autoimmune disorders or neoplasias. Diagnosis of IgA Vasculitis or current or history of nephrotic syndrome Average blood pressure (BP) > 150/90 mm Hg (systolic/diastolic). Clinical suspicion of IgAN with rapidly progressive glomerulonephritis (RPGN) based on KDIGO guidelines (KDIGO, 2021) Chronic Kidney Disease, either clinically suspected or based on biopsy, resulting from any condition or another glomerulopathy/podocytopathy other than IgAN. History of Type 1 Diabetes. Subjects with Type 2 diabetes are excluded if any of the following are present: Screening HbA1c of > 8%. Evidence of diabetic changes on kidney biopsy, performed for any reason. History of diabetic microvascular/macrovascular disease. Unstable anti-diabetic regimen Prior exposure to any antibody directed against APRIL. History of a previous severe allergic reaction including a history of severe hypersensitivity reaction to any monoclonal antibody. Received an investigational new drug within 28 days or 5 half-lives, whichever is longer, prior to Screening. Received systemic corticosteroid therapy including budesonide (Tarpeyo/Kinpeygo) for >14 days within 12 weeks prior to Screening. Use of systemic immunosuppressant medications Current severe infection requiring antimicrobials or history of recurrent, severe, infections as determined by the Investigator. Positive serology test for HIV or hepatitis infection. Received a live vaccination within 12 weeks prior to Screening or plan to have a live vaccination within 6 months after the last dose of study drug. Pregnancy or breastfeeding or intent to become pregnant or to donate sperm during the study period and until 24 weeks after last dose. Participation in another interventional trial with an investigational agent/device is prohibited during the course of this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BION-1301<br>600mg subcutaneous administration every 2 weeks for 104 weeks | Drug: BION-1301<br>* BION-1301 Pre-Filled Syringe (PFS) 600mg subcutaneous administration every 2 weeks for 104 weeks.<br>* Other names: Zigakibart;|
| Placebo Comparator: Placebo<br>subcutaneous administration every 2 weeks for 104 weeks | Drug: Placebo<br>* Placebo - PFS subcutaneous administration every 2 weeks for 104 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in proteinuria | The change in urine protein: creatinine ratio (UPCR) from baseline to Week 40. | 40 weeks or approximately 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in eGFR | The change in eGFR from baseline to Week 104. | 104 weeks or approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Diseases, Kidney Diseases, Chronic, Urological Diseases, Glomerulonephritis, Glomerular Disease, Glomerulonephritis, IGA, Glomerulopathy, Immunoglobulin Disease