IgA Nephropathy, Immunoglobulin A Nephropathy
Conditions
Keywords
Kidney Diseases, Kidney Diseases, Chronic, Urological Diseases, Glomerulonephritis, Glomerular Disease, Glomerulonephritis, IGA, Glomerulopathy, Immunoglobulin Disease
Brief summary
Safety and Efficacy of BION-1301 in Adults with IgA Nephropathy
Detailed description
Approximately 330 participants with eGFR ≥ 30 mL/min/1.73m\^2 and with biopsy-proven IgAN will be randomized to receive 600 mg Q2W BION-1301, Novartis FUB523, or a matched placebo for 104 weeks. An additional exploratory cohort, not included in the primary analysis, will be comprised of approximately 20 participants (10 participants per arm) with biopsy-confirmed IgAN and eGFR of ≥ 20 to \< 30 mL/min/1.73 m\^2. The exploratory cohort will be randomized using the same schema as the primary cohort. The primary objective of the study is to evaluate the effect of BION-1301 versus placebo on eGFR as measured by the change from Baseline in eGFR. Following completion of the 104-week treatment period, subjects may be eligible to enroll in an open-label extension (OLE) study to receive open-label treatment with BION-1301 under a separate protocol. Subjects who do not enroll in the OLE will enter the protocol-specified 24-week safety follow-up period. To facilitate study participation over this time period, other visits may be remote (away from study site) for participants who elect to self-administer the study drug.
Interventions
DRUGBION-1301
BION-1301 Pre-Filled Syringe (PFS) 600mg subcutaneous administration every 2 weeks for 104 weeks.
DRUGPlacebo
Placebo - PFS subcutaneous administration every 2 weeks for 104 weeks.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female participants 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 diagnosed within the past 10 years prior to Screening, that, in the opinion of the Investigator, is not due to secondary causes. A pseudonymized copy of the report must be available for review by the Sponsor or designee prior to randomization. If biopsy report within 10 years is not available, re-biopsy may be permitted upon discussion with the Sponsor. * eGFR ≥ 30 mL/min/1.73m\^2 at Screening based on the 2021 CKD-EPI equation. * Total urine protein ≥ 1.0 g/day or UPCR ≥ 0.7 g/g (700 mg/g), as measured from an adequate 24-hour urine collection at Screening by a central laboratory. * Stable on a maximally tolerated dose of angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin II receptor blockers (ARB) for at least 12 weeks prior to Screening unless intolerant to ACEi and ARB. May also be on a stable and well tolerated dose of sodium glucose cotransporter-2 inhibitors (SGLT2i), endothelin receptor antagonists (ERAs) and/or mineralocorticoid receptor antagonists (MRAs) for at least 12 weeks prior to Screening for the treatment of IgAN. Subjects are expected to stay on a stable dose of ACEi, ARB, SGLT2i, ERAs, and/or MRAs for the duration of the study.
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. * Current or history of nephrotic syndrome. * Received systemic corticosteroid therapy including budesonide (Tarpeyo/Kinpeygo) for \> 14 days within 12 weeks prior to Screening. * Use of systemic immunosuppressant medications. * IgG levels \< 6 g/L at Screening. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in eGFR | Baseline and 104 weeks or approximately 2 years | Change from Baseline to Week 104 in eGFR using the CKD-EPI 2021 creatinine equation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in proteinuria (natural log UPCR) | Baseline and 40 weeks or approximately 9 months | Change in urine protein: creatinine ratio (UPCR) from baseline to week 40 |
| Annualized rate of change in eGFR | 104 weeks or approximately 2 years | Annualized eGFR slope estimated over 104 weeks using the CKD-EPI 2021 creatinine equation |
| Effect of BION-1301 on specific clinical composite endpoints (30% eGFR reduction) | Baseline and Weeks 4, 12, 24, 40, 52, 64, 76, 88, and 104 | Percent of participants meeting the composite endpoint of experiencing at least 1 of the following during the study: * At least 30% reduction in eGFR sustained for at least 30 days * eGFR \< 15 mL/min/1.73m\^2, sustained for at least 30 days * Chronic dialysis, ≥ 30 days * Kidney transplantation * All-cause mortality |
| Effect of BION-1301 on specific clinical composite endpoints (40% eGFR reduction) | Baseline and Weeks 4, 12, 24, 40, 52, 64, 76, 88, and 104 | Percent of participants meeting the composite endpoint of experiencing at least 1 of the following during the study: * At least 40% reduction in eGFR sustained for at least 30 days * eGFR \< 15 mL/min/1.73m\^2, sustained for at least 30 days * Chronic dialysis, ≥ 30 days * Kidney transplantation * All-cause mortality |
| Percent Change in Proteinuria and Total Urine Protein | 40 weeks or approximately 9 months | Percent of participants achieving reduction of proteinuria to \< 1.0 g/day at Week 40 and a ≥ 25% decrease in total urine protein from Baseline |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Croatia, Czechia, France, Germany, Greece, India, Israel, Italy, Japan, Malaysia, Mexico, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed