study of the safety and efficacy of oms721 in patients with immunoglobulin a (iga) nephropathy

Conditions: IgA Nephropathy

Summary: the primary objective of this study is to evaluate the effect of oms721 on 24-hour urine protein excretion (upe) in iga nephropathy (igan) patients with high baseline proteinuria (high-risk proteinuria group; 24-hour upe ≥ 2 g/day) assessed at 36 weeks from baseline.

this is a phase 3, double-blind, randomized, placebo-controlled, study in patients aged 18 years and above with a biopsy-confirmed diagnosis of igan and with 24-hour upe that is \> 1 g/day. the purpose of this study is to evaluate the efficacy and safety of narsoplimab (oms721) compared to placebo on proteinuria and whether narsoplimab has the ability to slow disease progression in primary igan patients. the primary objective of the study is to evaluate proteinuria reduction as assessed by 24-hour upe at 36 weeks from baseline. the trial will continue beyond 36 weeks in a blinded fashion to provide confirmatory evidence of long-term efficacy based on the annualized slope of egfr over 24 months. the trial will enroll approximately 450 patients with 225 patients per arm, all having biopsy-proven igan with egfr≥30 ml/min/1.73m2 and 24 hour upe \>1g/day. the study duration for each patient is expected to last approximately 112 weeks.

Eligibility criteria:
inclusion criteria: * age 18 years or older at the onset of screening * biopsy confirmed diagnosis of igan within 8 years prior to screening * proteinuria of \> 1 g/day within 6 months prior to screening or upcr \> 0.75 by spot urine at screening * mean of two proteinuria measurements \> 1 g/day at baseline * estimated glomerular filtration rate of ≥ 30 ml/min/1.73 m² at screening and baseline exclusion criteria: * treatment with immunosuppressants (e.g., azathioprine or cyclophosphamide), or cytotoxic drugs, for iga within 8 weeks prior to screening. treatment with immunosuppressants or cytotoxic drugs for igan is not allowed during the run-in period. treatment with immunosuppressants are allowed if such treatment is for indications other than igan. * treatment with eculizumab within 8 weeks prior to screening. treatment with eculizumab is not allowed during the run-in period. * treatment with systemic corticosteroids within 8 weeks prior to screening. treatment with systemic corticosteroids is not allowed during the run-in period. * uncontrolled bp, a systolic bp of \> 150 mmhg and a diastolic bp of \> 100 mmhg at rest despite the combination of two or more anti-hypertensives including aceis, arbs, or direct renin inhibitors at screening and baseline * female patients who are pregnant, breast feeding, or planning to become pregnant up through 12 weeks after the last dose of study drug, including possible retreatments. males who are planning to father children up through 12 weeks after the last dose of study drug, including possible retreatments * clinical or biological evidence of type 1 diabetes mellitus (dm), or poorly controlled dm with hemoglobin a1c \> 7.5 or with evidence of diabetic nephropathy on biopsy, systemic lupus erythematosus, iga vasculitis (henoch-schonlein purpura), secondary igan, or other renal disease during screening and run-in * history of renal transplantation * have a known hypersensitivity to any constituent of the investigational product * rapidly progressive glomerulonephritis * significant abnormalities in clinical laboratory values * history of human immunodeficiency virus (hiv), evidence of immune suppression, active hcv infection (patients with positive anti-hcv antibody but a non-detected hcv rna pcr can enroll), hbv infection (patients with positive hbsag are excluded. for patients with isolated positive anti-hbc antibody, hbv dna test by pcr must be non-detectable to enroll). * diagnosis of a malignancy except for adequately treated and cured basal or squamous cell skin cancer, curatively treated in situ disease, or other cancer from which the patient has been disease-free for ≥ 5 years * have received any other investigational drug or device or experimental procedures and/or treatments within 30 days of the screening visit (sv) * initiation or change in dosing of sodium glucose co-transporter 2 inhibitors (sglt2i) during screening and run-in periods. however, a stable dose regimen established at least 8 weeks prior to screening is acceptable * treatment with tarpeyo™ (budesonide) or other approved treatments for igan within 6 months prior to screening. treatment with tarpeyo is not allowed during screening and run-in periods * treatment with kerendia® (finerenone) within 6 months prior to screening. treatment with kerendia is not allowed during screening and run-in periods * initiation of treatment with filspari™ (sparsentan), a dual endothelin angiotensin receptor antagonist (deara) or similar medication within three months prior to screening. a stable dose initiated at minimum 3 months before screening is acceptable and will take the place of acei/arb as background therapy

Keywords: iga nephropathy igan proteinuria chronic kidney disease igan autoantibodies egfr egfr slope upe narsoplimab