Safety, Efficacy and Tolerability of Ianalumab Versus Placebo, Combination With SoC Therapy, in Participants With Active Lupus Nephritis

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

• Adult male and female participants aged 18 years or older at the time of screening

• Weigh at least 35 kg at screening

• Have a confirmed clinical diagnosis of SLE according to European League AgainstRheumatism/American College of Rheumatology (EULAR/ACR) Systemic Lupus Erythematosus (SLE) classification criteria

• Have a positive anti-nuclear antibody (ANA) test result; ANA titer ≥ 1:80 atscreening visit based on central or local laboratory result

• Active LN at screening, as defined by meeting the 3 following criteria:

• Renal biopsy within 6 months prior to screening period indicating ISN/RPS class IIIor IV active glomerulonephritis with or without co-existing class V features, orpure class V membranous LN. If no biopsy was performed within 6 months prior toscreening period, a biopsy will need to be performed during the screening periodafter having met all other inclusion/exclusion criteria.

• UPCR ≥ 1.0 g/g on 24h urine collection at Screening

• eGFR ≥ 25mL/min/1.73 m2. Participants with eGFR < 30 mL/min/1.73 m2 require renalbiopsy during the screening period showing sclerosis in ≤ 50% of glomeruli

• Newly diagnosed participants as well as pre-treated LN participants (includingrefractory cases) can be included, as long as they are currently on, or willing toinitiate SoC induction therapy for LN using MPA

• Induction therapy, as defined by treatment including both high dosecorticosteroids and MPA, should be initiated prior to or on day ofrandomization

• Anti-malarial treatment at stable dosing prior to randomization is stronglyrecommended, in the absence of contraindications

• Participants on azathioprine treatment at Screening must be switched to MPAprior to randomization

• Receipt of at least one dose of pulse methylprednisolone i.v. (250 - 1000 mg per dayup to 3000 mg cumulative dose) or equivalent for treatment of current episode ofactive LN within 60 days prior randomization. Participant who cannot take the pulsei.v. corticosteroid therapy should directly start on 0.8-1.0 mg/day (max 80mg/day)oral predniso(lo)ne.

• Able to communicate well with the Investigator to understand and comply with therequirements of the study

Exclusion Criteria:

Participants meeting any of the following criteria are not eligible for inclusion in this study:

• Severe renal impairment as defined by i.) presence of oliguria (defined as adocumented urine volume <400 mL/24 hrs) or ii.) End-Stage Renal Disease (ESRD)requiring dialysis or transplantation

• Sclerosis in > 50% of glomeruli on renal biopsy

• Use of other investigational drugs within 5 half-lives of enrollment, or within 30days or until the expected pharmacodynamic effect has returned to baseline. Use ofcertain Traditional Chinese Medicines

• Prior use of ianalumab (ever); or prior use other B cell depleting therapy within 36weeks prior to randomization or if therapy was administered < 36 weeks prior torandomization, B cell count less than the lower limit of normal or patient's ownbaseline value prior to having received an earlier B cell-depleting therapy

• Prior treatment with any of the following within 12 weeks prior to randomization

• Belimumab, telitacicept, abatacept, TNF-α mAb, immunoglobulins (i.v./s.c.)plasmapheresis

• Any other immuno-suppressants (i.v. or oral cyclophosphamide, calcineurininhibitors, JAK inhibitors or other kinase inhibitors)

• Thalidomide treatment and/or methotrexate

• Combination of DMARDs

• Imidazole derivative (e.g., azathioprine, mizoribine) must be discontinued prior tostarting treatment with MPA

• Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within 12 weeks prior to randomization

• History of major organ transplant or hematopoietic stem cell/bone marrow transplantor are due to receive transplantation

• Any one of the following laboratory values at screening:

• Hemoglobin levels < 8.0 g/dL (< 5 mmol/L), or < 7.0 g/dL (< 4.3 mmol/L) ifrelated to participant's SLE such as in active hemolytic anaemia

• Platelet count < 25 x 1000/µL

• Absolute neutrophil count (ANC) < 0.8 x 1000/µL

• Active viral, bacterial or other infections requiring intravenous or intramusculartreatment for clinically significant infection or history of recurrent clinicallysignificant infection which in the opinion of the investigator will place theparticipant at risk for participation.

• History of known intolerance/hypersensitivity to MPA, oral corticosteroids, or anycomponent of the study drug(s) or its excipients

• Receipt of live/attenuated vaccine within a 4-week period prior to randomization

• History of primary or secondary immunodeficiency, including a positive HIV testresult

• History of malignancy of any organ system (other than localized basal cell carcinomaor squamous cell carcinoma of the skin or or in-situ cervical cancer), treated oruntreated, within the past 5 years, regardless of whether there is evidence of localrecurrence or metastases

• Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes),psychiatric or additional physical condition that the Investigator feels mayjeopardize the participants in case of participation in this study

• Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). Positive serology forhepatitis B surface antigen (HBsAg) excludes the participant

• Evidence of active tuberculosis (TB) infection (after anti-TB treatment,participants with history of TB may become eligible according to national localguidelines)

• Pregnant or nursing (lactating) women

• Women of child-bearing potential, defined as all women physiologically capable ofbecoming pregnant, unless they are using highly effective methods of contraceptionduring dosing and for 6 months after stopping of investigational medication

• Sexually active male participants, who do not agree to use barrier protection duringintercourse with women of child-bearing potential while taking study treatment

Other protocol -defined Inclusion/Exclusion may apply.