Study of safety, efficacy and tolerability of ianalumab versus placebo, in combination with Standard of care therapy, in participants with active lupus nephritis
- Conditions
- Health Condition 1: M321- Systemic lupus erythematosus withorgan or system involvement
- Registration Number
- CTRI/2023/06/053819
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
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 EULAR/ACR SLE classification criteria
--Have a positive anti-nuclear antibody (ANA) test 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 at Screening
---eGFR =25mL/min/1.73
--Participants must be currently on, or willing to initiate SoC induction therapy for LN according to the institutional practices using MPA (MMF or enteric-coated MPA sodium
--Receipt of at least one dose of pulse methylprednisolone i.v. (500-1000 mg) or equivalent for treatment of current episode of active LN
--ANA titer should be =1:80 at screening visit based on central laboratory result
--Able to provide signed informed consent
--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
--Treatment with any of the following within 12 weeks prior to randomization
---belimumab, abatacept, TNF-a 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 103/µL
---Absolute neutrophil count (ANC) <1.0 x 103/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
--Any surgical, medical, psychiatric or additional physical condition that may jeopardize 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method demonstrate superiority of ianalumab, compared to placebo, in combination with SoC, in achieving stable CRR at Week 72 in active lupus nephritis (ISN/RPS class III, IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous) participants on background SoC therapy.Timepoint: week 72
- Secondary Outcome Measures
Name Time Method superiority of ianalumab, compared to placebo- <br/ ><br>-in time to first occurrence of UPCR 0.5 or =50% reduction from baseline up to Week 72 <br/ ><br>-in achieving stable CRR at Week 72 <br/ ><br>-in reducing renal or extra-renal flares from Week 24 through Week 72 <br/ ><br>-in BILAG-2004 <br/ ><br>-in FACIT-Fatigue <br/ ><br>Timepoint: Week 72