Efficacy and safety of LNP023 compared with rituximab insubjects with idiopathic membranous nephropathy
- Conditions
- Health Condition 1: N042- Nephrotic syndrome with diffuse membranous glomerulonephritis
- Registration Number
- CTRI/2019/10/021809
- 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
1. Written informed consent must be obtained before any study assessment is performed.
2. Able to communicate well with the investigator, to understand and comply with the
requirements of the study.
3. Female or male adult (more than or equal to 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.
4. Anti-PLA2R antibody titer of more than or equal to 100 RU/mL at screening visit (based on the EuroImmun ELISA test).
5. Less than or equal to 50% reduction in both anti-PLA2R level and 24h urine protein between first measurement at screening or run-in visit and baseline.
6. Urine protein more than or equal to 3.5 g per 24h at run-in and baseline visits.
7. Estimated GFR (using the CKD-EPI formula)more than or equal to 45 mL per min per 1.73 m2 at screening visit.
8. Weight of at least 35 kg and body mass index (BMI) of at least 15 kg per m2.
9. 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. The dose of ACEi or ARB must be stable for at least 8 weeks prior to Day 1, defined as <25% dose change over this 8 week period.
10. 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.
11. Subject agrees to collect 24h urine sample at home and to bring it to the investigational
site at specific visits.
1. 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)
2. Diagnostic renal biopsy showing evidence of crescent formation in glomeruli, suggestive
of an alternative or additional diagnosis to primary idiopathic MN.
3. Previous treatment with B-cell depleting or B-cell modifying agents such as, but not
limited to rituximab, belimumab, daratumomab or bortezomib.
4. 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 less than or equal to 10 mg prednisolone for at least 90 days prior to Day 1
5. Administration of any live vaccination within 4 weeks prior to Day 1
6. Previous treatment with gemfibrozil or strong CYP2C8 inhibitors such as clopidogrel within 7 days prior to Day 1
7. Use of other investigational drugs within 30 days (e.g. small molecules) or 5 half-lives of
screening or until the expected pharmacodynamic effect has returned to baseline (e.g. biologics), whichever is longer; or longer if required by local regulations
8. History of malignancy of any organ system (other than localised basal cell carcinoma of
the skin or in-situ cervical cancer), treated or untreated, within the past 5 years prior to
screening start, regardless of whether there is evidence of local recurrence or metastases
9. History of clinically significant ECG abnormalities, or any of the following ECG
abnormalities at screening or baseline visit:
a. QTcF more than 450 msec (males)
b. QTcF more than 460 msec (females)
History of familial long QT syndrome or known family history of Torsades de Pointes
Use of agents known to prolong the QT interval unless they can be permanently
discontinued for the duration of the study
10. 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
11. Pregnancy or nursing (lactation), where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human
Chrorionic Gonadotropin (hCG) laboratory test
12. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic contraception during dosing and for 1 week after stopping of LNP023 or for 12 months after stopping rituximab. Basic
contraception methods include:
a. Barrier methods of contraception: Condom or Occlusive cap.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method