Clinical Trial Finder

Inclusion Criteria:

• - Kidney biopsy documentation of International Society of Nephrology (ISN)/Renal Pathology Society (RPS) proliferative nephritis: Class III or IV (with or without concomitant Class V) within the last 6 months prior to screening or performed during screening.

• - Urine Protein to Creatinine Ratio (UPCR) greater than or equal to (>=) 1.0 milligram/milligram (mg/mg) measured twice during screening.

• - Currently receiving prednisone equivalent dose of 1 milligram/kilogram/day (mg/kg/day) or less than or equal to (<=) 60 mg/day whichever is lower, or less.

Must be receiving prednisone equivalent of 10 mg/day or more at screening and randomization. Treated for >= 6 weeks with stable dosing >= 2 weeks prior to first administration of study intervention.

• - If receiving angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blockers (ARB), a stable dose for at least 2 weeks prior to first administration of study intervention.

• - Is recommended to be up-to-date on all age-appropriate vaccinations prior to screening per routine local medical guidelines.

For study participants who received locally-approved (and including emergency use-authorized) coronavirus disease 2019 (COVID-19) vaccines recently prior to study entry, follow applicable local vaccine labelling, guidelines, and standards-of-care for patients receiving immune-targeted therapy when determining an appropriate interval between vaccination and study enrolment.

Exclusion Criteria:

• - Comorbidities (other than Lupus Nephritis, example, asthma, chronic obstructive pulmonary disease) which have required 3 or more courses of systemic glucocorticoids within the previous 12 months.

• - Has other inflammatory diseases that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), psoriatic arthritis (PsA), RA/lupus overlap, psoriasis, Crohn's disease, or active Lyme disease.

• - Has received oral cyclophosphamide within 3 months or intravenous (IV) cyclophosphamide within 6 months prior to first administration of study intervention.

• - Has a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, before screening.

- COVID-19 infection: During the 6 weeks prior to baseline, have had any of the following (a) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (test positive), or (b) suspected SARS-CoV-2 infection (clinical features of COVID-19 without documented test results), or (c) close contact with a person with known or suspected SARS-CoV-2 infection

LN is a heterogeneous autoimmune disease that includes a broad spectrum of clinical forms, ranging from those with lesions confined to the skin (cutaneous lupus erythematosus [CLE]) to others that involve one or more vital internal organs (systemic lupus erythematosus [SLE]). Renal involvement due to SLE is termed LN. Nipocalimab (also referred to as JNJ-80202135 or M281) is a fully human aglycosylated immunoglobulin (Ig) G1 monoclonal antibody designed to selectively bind, saturate, and block the IgG binding site on the endogenous neonatal fragment crystallizable receptor (FcRn). By targeting the IgG binding site on FcRn, nipocalimab is expected to block the binding and, hence, recycling of IgG into circulation, resulting in a decrease in circulating IgG antibody levels, including pathogenic IgG autoantibodies and alloantibodies. The study will consist of a screening period (less than or equal to [<=] 8 Week), double-blind treatment period (52 Week), and a safety follow-up period (6 Week). Safety assessment will include adverse events (AEs), serious adverse events (SAEs), laboratory parameters (hematology and chemistry) and vital signs. The total duration of the main study is up to 66 weeks.

Arms

Placebo Comparator: Group 1: Placebo

Participants will receive placebo intravenously (IV) every two weeks (q2w) from Week 0 through Week 50 along with standard-of-care treatment of mycophenolate mofetil (MMF) or mycophenolic acid (MPA) and glucocorticoid. Participants who will complete the assessments at Week 52 and have achieved complete renal response (CRR) may have the option to participate in the long-term extension (LTE) until unblinding of the study.

Experimental: Group 2: Nipocalimab Dose 1

Participants will receive nipocalimab dose 1 IV q2w from Week 0 through Week 50 along with standard-of-care treatment of MMF or MPA and glucocorticoid. Participants who will complete the assessments at Week 52 and have achieved CRR may have the option to participate in the LTE of the study.

Experimental: Group 3: Nipocalimab Dose 2

Participants will receive nipocalimab dose 2 IV q2w from Week 0 through Week 50 along with standard-of-care treatment of MMF or MPA and glucocorticoid. Participants who will complete the assessments at Week 52 and have achieved CRR may have the option to participate in the LTE of the study.

Interventions

Other: - Placebo

Placebo will be administered intravenously.

Drug: - Nipocalimab

Nipocalimab dose 1 and dose 2 will be administered intravenously.

Drug: - Standard-of-care treatment

Standard-of-care treatment including MMF or MPA and glucocorticoids will be administered intravenously through Week 52.