Study of Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients

Inclusion Criteria:

• Male and female patients ≥ 18 years of age with an eGFR level and biopsy-confirmedIgA nephropathy as follows:

• For patients eGFR* ≥ 45ml/min/1.73m2, a qualifying biopsy performed within the last 5 years is required.

• For patients with eGFR* 30 to <45ml/min/1.73m2, a qualifying biopsy performed within 2 years with < 50% tubulointerstitial fibrosis is required.

• For patients with eGFR* 20 to <30ml/min/1.73m2, a qualifying biopsy performed at anytime.

In all cases, if a historical biopsy is not available, one may be performed during screening. *eGFR calculated using the CKD-EPI formula (or modified MDRD formula according to specific ethnic groups and local practice guidelines)

• Proteinuria due to primary diagnosis of IgA nephropathy as assessed at screening byUPCR ≥1 g/g (113 mg/mmol) sampled from FMV or 24h urine collection, as well as atthe completion of the run-in period by UPCR ≥1 g/g (113 mg/mmol) calculated as the (geometric) mean of two 24h urine collections obtained within 14 days of each otherat baseline.

• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection isrequired prior to the start of study treatment. If the patient has not beenpreviously vaccinated, or if a booster is required, vaccine should be givenaccording to local regulations at least 2 weeks prior to first study drugadministration. If study treatment has to start earlier than 2 weeks postvaccination, prophylactic antibiotic treatment should be initiated.

• If not previously vaccinated, vaccination against Haemophilus influenzae infectionsshould be given, if available and according to local regulations, at least 2 weeksprior to first study drug administration.

• All patients must have been on supportive care including stable dose regimen of ACEior ARB at either the locally approved maximal daily dose or the maximally tolerateddose (per investigators' judgment) for approximately 90 days before first study drugadministration. In addition, if patients are taking diuretics, otherantihypertensive medication, or other background medication for IgAN, the dosesshould also be stabilized for approximately 90 days prior to the first dosing ofstudy treatment.

Exclusion Criteria:

• Any secondary IgAN as defined by the investigator; secondary IgAN can be associatedwith cirrhosis, celiac disease, Human Immunodeficiency Virus (HIV) infection,dermatitis herpetiformis, seronegative arthritis, small-cell carcinoma, lymphoma,disseminated tuberculosis, bronchiolitis obliterans, and inflammatory bowel disease,familial mediterranean fever, etc.

• Sitting office SBP >140 mmHg or DBP >90 mmHg at the randomization visit

• Patients previously treated with immunosuppressive or other immunomodulatory agentssuch as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab,canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS),cyclosporine, tacrolimus, sirolimus, everolimus, or systemic corticosteroidsexposure (>7.5 mg/d prednisone/prednisolone equivalent) within 90 days (or 180 daysfor rituximab) prior to first study drug administration. Participants previously orcurrently treated with oral budesonide. Participants treated with endothelin (receptor) antagonists within 90 days prior to first study drug administration.

• Prior use of iptacopan (LNP023) or prior enrollment in any other LNP023 clinicaltrial where study drug was taken, including matching placebo

• History of recurrent invasive infections caused by encapsulated organisms, such asmeningococcus and pneumococcus.

• Active systemic bacterial, viral (including COVID-19) or fungal infection within 14days prior to study drug administration.

Other protocol-defined inclusion/exclusion criteria may apply.