a study to evaluate the efficacy and safety of sefaxersen (ro7434656) in participants with primary immunoglobulin a (iga) nephropathy at high risk of progression

Conditions: Primary IgA Nephropathy

Summary: the purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of sefaxersen (ro7434656), a novel antisense oligonucleotide (aso) therapy in participants with primary iga nephropathy (igan) who are at high risk of progressive kidney disease despite optimized supportive care.


Eligibility criteria:
inclusion criteria: * primary igan, as evidenced by a kidney biopsy performed within 10 years prior to or during screening, without known secondary cause * treatment with maximum tolerated doses of angiotensin-converting enzyme (ace) inhibitors or angiotensin ii receptor blockers (arbs) for at least 90 days immediately prior to screening, except for interruptions due to illness (not greater than 7 consecutive days), unless the potential participant is intolerant to these medications * urine protein-to-creatinine ratio (upcr) ≥ 1 gram per gram (g/g) or urine protein excretion ≥ 1 gram per day (g/day) (with upcr ≥ 0.8 g/g), all measured from a 24-hour urine collection during screening * egfr ≥ 20 ml/min/1.73 m\^2, as calculated by the 2021 chronic kidney disease epidemiology collaboration (ckd-epi) creatinine equation (inker et al. 2021a) * vaccination against neisseria meningitidis, streptococcus pneumoniae and haemophilus influenzae according to national vaccination recommendations * female participants of childbearing potential must use adequate contraception 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 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 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