A Study to Evaluate the Efficacy and Safety of Sefaxersen (RO7434656) in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression

Exclusion Criteria

• •Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 12 weeks after the final dose of sefaxersen
• •Histopathologic or other evidence of another autoimmune glomerular disease
• •Presence of ≥ 50% crescents on kidney biopsy, sustained doubling of serum creatinine within 3 months prior to screening, or rapidly progressive glomerulonephritis in the opinion of the investigator
• •History of kidney transplantation
• •Glycated Hemoglobin (HbA1c) ≥ 6.5% or a clinical diagnosis of diabetes mellitus of any type
• •Systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg from the average of two measurements performed at least 1 minute apart during screening
• •Initiation of sodium-glucose cotransporter-2 (SGLT2) inhibitors within 16 weeks prior to screening or during screening
• •Initiation of endothelin receptor antagonists within 90 days prior to screening or during screening
• •Initiation of mineralocorticoid receptor antagonists or non-dihydropyridine calcium channel blockers within 90 days prior to screening or during screening
• •Use of herbal therapies within 90 days prior to or during screening
• •Treatment with investigational therapy within 28 days prior to screening or 5.5 drug-elimination half-lives of that investigational product prior to screening
• •Treatment with an investigational therapy planned during the treatment period
• •Previous treatment with sefaxersen
• •Treatment with oral or intravenous (IV) corticosteroids with a dose equivalent to ≥ 7.5 milligrams per day (mg/day) of prednisone for 7 days or equivalent to ≥ 5 mg/day of prednisone for 14 days within 90 days prior to screening
• •Treatment with corticosteroids with systemic effects during screening
• •Treatment with a systemic calcineurin inhibitor within 2 months prior to screening or during screening
• •Treatment with anti-CD20 therapy within 9 months of screening or during screening
• •Treatment with other systemic immunosuppressive agents within 6 months of randomization including, but not limited to, complement inhibitors, alkylating agents (e.g., cyclophosphamide or chlorambucil), azathioprine, or mycophenolate
• •Planned major procedure or major surgery during screening or the study
• •Substance abuse within 12 months prior to screening or during screening
• •Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study
• •History of malignancy within \< 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• •Usage of Glucagon-like Peptide-1 (GLP-1)-based therapy (i.e., GLP-1 mono-agonists, GLP-1/GIP dual agonists, etc.) within 90 days prior to screening or during screening, or intent to initiate during the study period