Atacicept in subjects with IgA Nephropathy: a Phase 2b/3, Multi-part, randomized, double-blinded, placebo- controlled trial

INTERVENTION: Study sites: The National Hospital of Sri Lanka, Colombo North Teaching Hospital, Kandy National Hospital, Jaffna Teaching Hospital, Kurunegala Teaching Hospital. Intervention: The study is comprised of Parts A, B, C, and D. Parts C and D are the Phase 3 portion of the study. Sri Lanka is only participating in parts C and D of the study. For Part C of the study, subjects will be randomized 1:1 to receive once weekly subcutaneous (SC) injections of Atacicept 150 mg or placebo for 104 weeks. Subjects who complete the 104‐week double‐blind treatment period will be eligible for a 52‐week open‐label extension (Part D) in which subjects will be given 150 mg atacicept once weekly SC injections. This will be followed by a 26‐week safety follow‐up period. The matched placebo product contains trehalose and sodium acetate as a buffer. An interactive web response system (IWRS) will be used to randomize a subject to study drug assignment. Once a subject meets the eligibility criteria, the subject will be randomly assigned to the treatment assignment. During Part C, this study will be double blinded for all subjects and investigators. Study drugs (atacicept or placebo) will not be distinguishable from each other. Each kit will be labeled by the manufacturer with a unique kit number; labeling will not indicate whether the medication is atacicept or placebo. Blinded treatment kit numbers will be obtained. through the IWRS. Subjects in Atacicept and placebo groups will continue to receive stable background standard of care during this trial. The administration will be done subcutaneously using a pre‐filled syringe. Only the participants or their family members/caregivers who receive appropriate training will be allowed to administer the medication. CONDITION: IgA Nephropathy PRIMARY OUTCOME: Change from baseline in urine protein to creatinine ratio (UPCR). ; UPCR based on 24‐hour urine collection.; [Baseline, 36 Weeks]; SECONDARY OUTCOME: Annualized rate of change in estimated glomerular filtration rate (eGFR) [Baseline, Week 52, 104]; Serum galactose deficient IgA1 (Gd‐IgA1) levels [Baseline, Weeks 36, 52, and 104]; Composite kidney failure endpoint defined as experiencing at least one of the following during the study:; • At least a 30% reduction in eGFR sustained for at least 30 days; • eGFR <15 mL/min/1.73m2 sustained for at least 30 days; • Chronic dialysis =30 days; • Kidney transplantation; • Death from kidney failure; [Over 104 weeks]; INCLUSION CRITERIA: • Male or female of greater than or equal to 18 years of age. • Total urine protein excretion greater than 1.0 g per 24‐hour or urine protein to creatinine ratio (UPCR) greater than 1.0 mg/mg based on a 24‐hour urine sample during the Screening Period Diagnosis of IgAN as demonstrated by renal biopsy conducted within 10 years. • eGFR greater than or equal to 30 mL/min/1.73 m2, as per the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation. • On a stable prescribed regimen of RAASi for at least 12 weeks that is at the maximum labelled or tolerated dose at Screening. • Systolic blood pressure less than or equal to 150 mmHg and diastolic blood pressure less than or equal to 90 mmHg.