A Study of Zigakibart in Adults With IgA Nephropathy

Inclusion Criteria:

• Male and female participants aged ≥ 18 years at the time of signing the informedconsent form (ICF) prior to initiation of any study specific activities/procedures.

• Biopsy-proven IgAN diagnosed within the past 10 years prior to Screening, that, inthe opinion of the Investigator, is not due to secondary causes. A pseudonymizedcopy of the report must be available for review by the Sponsor or designee prior torandomization. If biopsy report within 10 years is not available, re-biopsy may bepermitted 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 anadequate 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 toScreening unless intolerant to ACEi and ARB. May also be on a stable and welltolerated dose of sodium glucose cotransporter-2 inhibitors (SGLT2i), endothelinreceptor antagonists (ERAs) and/or mineralocorticoid receptor antagonists (MRAs) forat least 12 weeks prior to Screening for the treatment of IgAN. Subjects areexpected to stay on a stable dose of ACEi, ARB, SGLT2i, ERAs, and/or MRAs for theduration of the study.

• Screening weight of 45 to 150 kg.

• Men and women of childbearing potential (WOCBP; per Clinical Trials Facilitation andCoordination Group [CTFG] 2020) must agree to follow protocol-specifiedcontraception guidance from Screening through approximately 5 half-lives (24 weeks)after the final dose of study drug. Use of hormonal contraceptive agents must havebeen initiated > 1 month prior to first dose of study drug.

• Provide written informed consent and be willing to comply with study visits andprocedures.

Exclusion Criteria:

• Secondary forms of IgAN as determined by the Investigator, in the setting ofsystemic disorders, infections, autoimmune disorders or neoplasias.

• Diagnosis of IgA Vasculitis.

• Current or history of nephrotic syndrome.

• Average blood pressure > 150/90 mm Hg (systolic/diastolic) from 3 readings obtainedat the initial Screening visit. If blood pressure is too high, the 3 readings may berepeated once within the Screening period if clinically appropriate as per theInvestigator.

• Clinical suspicion of IgAN with rapidly progressive glomerulonephritis (RPGN) basedon KDIGO guidelines

• Chronic Kidney Disease, either clinically suspected or based on biopsy, resultingfrom any condition or another glomerulopathy/podocytopathy other than IgAN.

• History of Type 1 Diabetes.

• Participants with Type 2 diabetes are excluded if any of the following are present:

• Screening HbA1c (glycated hemoglobin) of > 8%.

• Evidence of diabetic changes on kidney biopsy, performed for any reason.

• History of diabetic microvascular disease (retinopathy, neuropathy,nephropathy) and/or macrovascular disease (atherosclerotic heart disease,peripheral vascular disease, cerebrovascular disease).

• Unstable anti-diabetic regimen:

• Prior exposure to any therapy directed against APRIL.

• History of a previous severe allergic reaction with generalized urticaria,angioedema, or anaphylaxis, including a history of allergy or hypersensitivity toany component of BION-1301, or history of severe hypersensitivity reaction to anymonoclonal antibody.

• Received an investigational new drug within 28 days or 5 half-lives, whichever islonger, 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.

• Any confirmed or suspected immunosuppressive or immune-deficient state, includingbut not limited to common variable immunodeficiency (CVID), HIV infection orasplenia, history of bone marrow or organ transplantation with exception of cornealtransplants.

• Current severe infection requiring antimicrobials or history of recurrent, severe,infections as determined by the Investigator.

• Positive serology test for hepatitis A virus IgM antibodies (anti-HAV IgM),hepatitis B surface antigen (HBsAg), detectable hepatitis B virus (HBV) DNA,hepatitis C virus (HCV) antibodies (participants who completed treatment and arepersistently antibody be allowed), or antibodies to HIV-1 and/or HIV-2 at Screening.

• Received a live vaccination within 12 weeks prior to Screening or plan to have alive vaccination within 6 months after the last dose of study drug.

• History of malignancy unless cancer free for at least 5 years or non-melanoma skincancer that was completely resected. A participant with curatively treated cervicalcarcinoma in situ is eligible for the study. Participants with low-risk prostatecancer (i.e., Gleason score < 7 and prostate specific antigen < 10 ng/mL) areallowed.

• Pregnancy or breastfeeding or intent to become pregnant or to donate sperm duringthe study period and until 24 weeks after last dose.

• History or evidence of any other clinically significant disorder, condition,disease, or laboratory finding that, in the Investigator's assessment, would placethe participant at unacceptable risk, limit compliance with study requirements, orconfound interpretation of study results.

• IgG levels < 6 g/L at Screening.

• Participation in another interventional trial with an investigational agent/deviceis prohibited during the course of this study.