Efficacy and Safety of LNP023 Compared With Rituximab in Subjects With Idiopathic Membranous Nephropathy

A Randomized, Treatment Open-label, Dose-blinded Parallel Group, Three Arm, Proof-of-concept Clinical Trial to Investigate the Efficacy and Safety of LNP023 Compared With Rituximab in the Treatment of Subjects With Idiopathic Membranous Nephropathy

ClinicalTrials.gov Identifier: NCT04154787

Novartis Reference Number: CLNP023D12201

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

This is a randomized, treatment open-label, dose-blinded parallel group, three arm, proof-of-concept, non-confirmatory study evaluating the efficacy and safety of LNP023 compared with rituximab in subjects with MN who are at high risk of disease progression defined on the basis of antibody anti-PLA2R titre and proteinuria. The screening period will last up to 12 weeks and the whole study will last up to 65 weeks. Approximately 72 subjects will be randomized to one of three arms. Treatment with LNP023 or rituximab is open label, although dose of LNP023 will be blinded for subjects, investigators and sponsor. Both of the low and high-dose LNP023 arms have a 4-week period of initial dose treatment, followed by a 20-week period of full dose treatment to evaluate the effect of the different LNP023 doses on complement biomarkers. Efficacy will be evaluated at the end of the 24-week treatment period. The randomization ratio is 1:1:1; low-dose (regimen A) LNP023: high dose (regimen B) LNP023: rituximab.

Condition 
Glomerulonephritis, Membranous
Phase 
Phase 2
Overall status 
Recruiting
Enrollment count 
72 participants
Start date 
Nov 23, 2019
Completion date 
Oct 12, 2022
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
LNP023
Investigation of low and high LNP023 dose regimens
Drug
Rituximab
Comparison of rituximab dose

Eligibility Criteria

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
Urine protein ≥ 3.5 g/24h at screening and baseline visits
≤50% reduction in both anti-PLA2R level and 24h urine protein between screening and baseline
Estimated GFR (using the CKD-EPI formula) ≥ 45 mL/min per 1.73 m2 at screening
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.

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
Known contra-indications for the use of rituximab, including hypersensitivity to the active substance or to murine proteins, or to any of the excipients (sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid, water for injections). Other contra-indications for the use of rituximab, including active, severe infection, patients in a severely immunocompromised state, severe heart failure (NYHA Class IV) or severe, uncontrolled cardiac disease.

Study Locations

Argentina
Novartis Investigative Site
Recruiting
Caba, C1280AEB
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
Ciudad Autonoma de Bs As, C1015ABO
-
Argentina
Czechia
Novartis Investigative Site
Recruiting
Plzen-Bory, 305 99
-
Czechia
Novartis Investigative Site
Recruiting
Praha, 12808
-
Czechia
France
Novartis Investigative Site
Recruiting
Montpellier, 34295
-
France
Novartis Investigative Site
Recruiting
Paris cedex 15, 75015
-
France
Novartis Investigative Site
Recruiting
Paris, 75020
-
France
Germany
Novartis Investigative Site
Recruiting
Berlin, 13353
-
Germany
Novartis Investigative Site
Recruiting
Dresden, 01307
-
Germany
Novartis Investigative Site
Recruiting
Essen, 45147
-
Germany
Novartis Investigative Site
Recruiting
Hamburg, 20246
-
Germany
India
Novartis Investigative Site
Recruiting
New Delhi, 110 017
Delhi
India
Novartis Investigative Site
Recruiting
New Delhi, 110 060
Delhi
India
Novartis Investigative Site
Recruiting
Hyderabad, 500034
Telangana
India
Novartis Investigative Site
Recruiting
DehraDun, 248001
Uttarakhand
India
Novartis Investigative Site
Recruiting
New Delhi, 110029
-
India
Singapore
Novartis Investigative Site
Recruiting
Singapore, 119228
-
Singapore
Novartis Investigative Site
Recruiting
Singapore, 169608
-
Singapore
Novartis Investigative Site
Recruiting
Singapore, 308433
-
Singapore
Spain
Novartis Investigative Site
Recruiting
L Hospitalet De Llobregat, 08907
Barcelona
Spain
Novartis Investigative Site
Recruiting
Valencia, 46017
Comunidad Valenciana
Spain
Novartis Investigative Site
Recruiting
Madrid, 28041
-
Spain
United Kingdom
Novartis Investigative Site
Recruiting
Salford, M6 8HD
Manchester
United Kingdom
Novartis Investigative Site
Recruiting
Cardiff, CF14 4XW
-
United Kingdom
Novartis Investigative Site
Recruiting
Leicester, LE5 4PW
-
United Kingdom
Novartis Investigative Site
Recruiting
London, NW3 2QG
-
United Kingdom
Novartis Investigative Site
Recruiting
Manchester, M13 9WL
-
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

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