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

• Status: Not yet recruiting
• Trial end date: 2029-09-03
• Target enrollment: 0
• Participant gender: All

Summary

This trial will evaluate efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or every 12 weeks (q12w) compared to placebo, in combination with SoC, in adult participants with active LN

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals

Criteria

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 baseline

Weigh at least 35 kg at screening

Have a confirmed clinical diagnosis of SLE according to European League Against Rheumatism/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 at screening visit based on central laboratory result

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

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

• UPCR ≥1.0 on 24h urine collection at Screening

• eGFR ≥25mL/min/1.73 m2

Participants must be currently on, or willing to initiate SoC induction therapy for LN according to the institutional practices using MPA

Receipt of at least one dose of pulse methylprednisolone i.v. (500-1000 mg) or equivalent for treatment of current episode of active LN during past 60 days prior screening

Able to communicate well with the Investigator to understand and comply with the requirements 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.) Stage 4 Chronic Kidney Disease (CKD), or ii.) presence of oliguria (defined as a documented urine volume <400 mL/24 hrs), or iii.) 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 30 days or until the expected pharmacodynamic effect has returned to baseline

Prior use of any B cell depleting therapy within 36 weeks prior to randomization or as long as B cell count <50 cells/μL

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

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

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

• thalidomide treatment and/or one of the following DMARDs: methotrexate or an imidazole derivative (e.g., azathioprine, mizoribine)

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

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

Any one of the following laboratory values at screening:

• Hemoglobin levels <8.0 g/dL

• Platelet count <75 x 1000/µL

• Absolute neutrophil count (ANC) <1.0 x 1000/µL

Active viral, bacterial or other infections requiring systemic treatment at the time of screening, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms

History of known intolerance/hypersensitivity to MPA, oral corticosteroids, or any component 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 test result

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

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

Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). Positive serology for hepatitis 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 guidelines).

Pregnant or nursing (lactating) women

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