Study of efficacy and safety of LNP023 in primary IgA nephropathy patients
- Conditions
- Health Condition 1: N027- Recurrent and persistent hematuriawith diffuse crescentic glomerulonephritis
- Registration Number
- CTRI/2021/07/034652
- 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-Male and female patients greater than or equal to 18 years of age with an eGFR level and
biopsy-confirmed IgA nephropathy as follows
a- For patients eGFR greater than or equal to 45mL per min per 1.73m2, a qualifying biopsy
performed within the last 5 years is required
b-For patients with eGFR 30 to less than 45mL per min per 1.73m2, a qualifying
biopsy performed within 2 years with less than 50 percent tubulointerstitial
fibrosis is required
c-For patients with eGFR 20 to less than 30mL per min per 1.73m2, a qualifying biopsy performed at any time. In all cases, if a historical biopsy is not available, one may be performed during screening.
2-Proteinuria due to primary diagnosis of IgA nephropathy as assessed at screening by UPCR >=1 g/g (113 mg/mmol) sampled from FMV or 24h urine
collection, as well as at the completion of the run-in period by UPCR >=1 g/g (113 mg/mmol) calculated as the (geometric) mean of two 24h urine collections obtained within 14 days of each other at baseline.
3-Vaccination against Neisseria meningitidis types A, C, Y and W-135 is required at least 2
weeks prior to first study drug administration. Vaccination against N. meningitidis type B
should be conducted if available and acceptable by local regulations, at least 2 weeks prior
to first study drug administration.
4-Vaccination against the prevention of Streptococcus pneumoniae and Haemophilus
influenzae, if available and acceptable by local regulations, at least 2 weeks prior to first
study drug administration.
5-All patients must have been on supportive care including stable dose regimen of ACEi or ARB at either the locally approved maximal daily dose or
the maximally tolerated dose (per investigatorsâ?? judgment) for at least 90 days before first study drug administration. In addition, if patients are taking diuretics, other antihypertensive medication or other background medication for IgAN, the doses should also be stabilized for at least 90 days prior to the first dosing of study treatment.
1-Secondary IgAN as defined by the investigator; secondary IgAN can be associated with
cirrhosis, celiac disease, Human Immunodeficiency Virus (HIV) infection, herpetiformis,
seronegative arthritis, small-cell carcinoma, lymphoma, disseminated tuberculosis,
bronchiolitis obliterans, and inflammatory bowel disease, familial mediterranean fever,
etc.
2-Evidence of urinary obstruction or difficulty in voiding; any urinary tract disorder other
than IgAN at screening and before first study drug administration.
3-Current or planned usage of any herbal medications for IgAN disease progression, such as
but not limited to Lei Gong Teng.
4-Current acute kidney injury (AKI) defined by AKIN criteria within 4 weeks of screening
Mehta et al 2007.
5-Presence of rapidly progressive glomerulonephritis (RPGN) as defined by 50% decline in
eGFR within 3 months prior to screening.
6-Sitting office SBP >140 mmHg or DBP >90 mmHg at the randomization visit.
7-Patients previously treated with immunosuppressive or other immunmodulatory agents
such as cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab,
hydroxychloroquine, mycophenolate mofetil (MMF) or mycophenolate sodium MPS,
cyclosporine, tacrolimus, sirolimus, everolimus, or systemic corticosteroids exposure >10
mg per d prednisone per prednisolone equivalent within 90 days prior to first study drug
administration.
8-Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days,
whichever is longer.
9-Prior use of LNP023 or prior enrollment in any other LNP023 clinical trial where study
drug was taken, including matching placebo.
10-All transplanted patients any solid organ transplant, including bone marrow transplant.
11-History of recurrent meningitis, history of meningococcal infections.
12-Major concurrent comorbidities including but not limited to advanced cardiac disease
e.g. New York heart association NYHA class IV, severe pulmonary disease e.g., severe pulmonary hypertension World Health Organization WHO class IV, or hepatic disease e.g., active hepatitis that in the opinion of the investigator precludes participants participation in the study.
13-Any medical condition deemed likely to interfere with the patientâ??s participation in the
study, or likely to cause serious adverse events during the study.
14-Active systemic bacterial, viral or fungal infection within 14 days prior to study drug
administration.
15-Presence of fever Greater than 38 degree C 100.4 degree F within 7 days prior to study drug administration.
16-History of HIV infection.
17-History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.
18-Liver disease or liver injury as indicated by abnormal liver function tests at screening as
defined below. ALT SGPT, AST SGOT, GGT, alkaline phosphatase and serum bilirubin will be tested.
a-Any single parameter of ALT, AST, GGT, alkaline phosphatase must not exceed 3 x
upper limit of normal ULN b-Serum bilirubin must not exceed 2 x ULN
19-History of malignancy of any organ system other than
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To demonstrate superiority of LNP023 vs. placebo in the reduction of proteinuria at 9 <br/ ><br>months by measuring UPCR sampled from a 24h urine collectionTimepoint: Log-transformed ratio to baseline in UPCR (sampled from 24h urine collection) at 9 months of treatment.
- Secondary Outcome Measures
Name Time Method To assess the effect of LNP023 vs. placebo on the proportion of study participants reaching proteinuria below 1g/g of UPCR (sampled from 24h urine collection) at 9 months. <br/ ><br>Timepoint: Proportion of participants reaching UPCR (sampled from 24h urine collection) at 9 months;To assess the effectof LNP023 vs. placebo <br/ ><br>on the change from baseline to 9 months in <br/ ><br>fatigue scale measured by the FACITFatigue <br/ ><br>questionnaireTimepoint: Change from baseline to 9 months in the <br/ ><br>fatigue scale measured by the FACITFatigue <br/ ><br>questionnaire.;To evaluate the effect of LNP023 vs. placebo on renal disease progression measured by the annualized total slope of eGFR decline over 1 year for patients who have completed at least 9 months treatment.Timepoint: Annualized total eGFR slope estimated over <br/ ><br>12 months treatment.