Is Atacicept efficacious and safe when compared to a placebo in reducing proteinuria in adult participants with Ig A Nephropathy (IgAN) and persistent proteinuria despite being on a maximally tolerated dose (MTD) of a Renin–angiotensin system inhibitor (RASi)?

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.

• 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.

• IgAN secondary to another condition (e.g., liver cirrhosis), or other causes of mesangial IgA deposition including IgA vasculitis (i.e., Henoch-Schonlein purpura), systemic lupus erythematosus (SLE), dermatitis herpetiformis, ankylosing spondylitis. • Total urine protein excretion greater than or equal to 5g per 24-hour or urine protein to creatinine ratio (UPCR) greater than or equal to 5 mg/mg based on a 24-hour urine sample during the Screening Period • Evidence of rapidly progressive glomerulonephritis (loss of greater than or equal to 50% of eGFR within 3 months of screening) • Evidence of nephrotic syndrome within 6 months of screening (serum albumin <30g/L in association with UPCR >3.5 mg/mg • Renal or other organ transplantation prior to or expected during the study. • Concomitant chronic renal disease in addition to IgAN • Uncontrolled diabetes, defined as hemoglobin-A1c (HbA1c) >7.5% at screening. • History of tuberculosis (TB), untreated latent TB infection (LTBI), or evidence of active TB determined by a positive Quantiferon test. • Participation in the Phase 2b (Parts A and B) study or any previous treatment with atacicept