Efficacy and safety of LNP023 compared with rituximab in subjects with idiopathic membranous nephropathy.

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 72

Inclusion Criteria

• Female or male adult (=18 years) subjects at screening visit with a diagnosis of idiopathic (primary) MN confirmed by renal biopsy within 24 months prior to screening. A renal biopsy may be taken at any time during the run-in period to confirm the diagnosis of MN and facilitate subject eligibility, if the most recent biopsy was performed greater than 24 months prior to the screening visit.
• Anti-PLA2R antibody titer of = 100 RU/mL at screening visit (based on the EuroImmun ELISA test)
• Urine protein = 3.5 g/24h at run-in and baseline visits
• =50% reduction in both anti-PLA2R level and 24h urine protein between first measurement at screening or run-in visit and baseline
• Estimated GFR (using the CKD-EPI formula) = 45 mL/min per 1.73 m2 at run-in visit
• Receiving stable dose at the maximum recommended dose according to local guidelines or maximum tolerated dose of ACEi and/or ARB and/or statins and/or diuretics for at least 8 weeks prior to Day 1
• Vaccination against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae (in accordance with local guidelines) at least 28 days prior to Day 1 and no longer than 5 years prior to Day 1

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 57
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

• Secondary causes of MN, e.g. systemic autoimmune diseases, solid or haematological malignancies, infections or chronic intake of drugs (e.g. gold salts, NSAIDs, penicillamines)
• Diagnostic renal biopsy showing evidence of crescent formation in glomeruli, suggestive of an alternative or additional diagnosis to primary idiopathic MN
• Previous treatment with B-cell depleting or B-cell modifying agents such as, but not limited to rituximab, belimumab, daratumomab or bortezomib
• Previous treatment with immunosuppressive agents such as cyclophosphamide, chlorambucil, mycophenolate mofetil (or equivalent), cyclosporine, tacrolimus or azathioprine within 90 days prior to Day 1. Low dose systemic corticosteroid therapy is permitted, though the subject should have been on stable dose equivalent to =10 mg prednisolone for at least 90 days prior to Day 1
• Previous treatment with gemfibrozil or strong CYP2C8 inhibitors such as clopidogrel within 7 days prior to Day 1
• Presence or suspicion (based on judgment of the investigator) of active infection within 30 days prior to Day 1, or history of severe recurrent bacterial infections

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of high dose LNP023 compared with rituximab;Secondary Objective: - To assess the safety and tolerability of low and high dose of LNP023<br>- To assess the relationship between LNP023 systemic drug exposure and pharmacodynamics, mode-of-action markers and clinical efficacy<br>- To assess the difference in response between low (regimen A) and high (regimen B) dose of LNP023<br>- To assess the effect of LNP023 compared with rituximab on proteinuria remission and renal function<br>- To assess the pharmacokinetics of LNP023<br>;Primary end point(s): Ratio between baseline UPCR and UPCR at 24 weeks of treatment (from 24h urine collection);Timepoint(s) of evaluation of this end point: Baseline, Day 113 and Day 169

Secondary Outcome Measures

Name	Time	Method

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