Study of Safety and Efficacy of LNP023 in Patients With Kidney Disease Caused by Inflammatio
- Conditions
- Patients with IgA nephropathyIgA nephropathyD41.0
- Registration Number
- LBCTR2020023394
- Lead Sponsor
- ovartis Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Other
- Sex
- All
- Target Recruitment
- 4
Inclusion Criteria:
•Female and male patients above 18 years of age with a biopsy-verified IgA nephropathy and where the biopsy was performed within the prior three years.
•Patients must weigh at least 35 kg to participate in the study, and must have a body mass index (BMI) within the range of 15 - 38 kg/m2. BMI = Body weight (kg) / [Height (m)]2
•Measured Glomerular Filtration Rate (GFR) or estimated GFR (using the CKD-EPI formula) =30 mL/min per 1.73 m2
•Urine protein =1 g/24hr at screening and =0.75 g / 24h after the run- in period
•Vaccination against Neisseria meningitidis types A, C, Y and W-135 is required at least 30 days prior to first dosing with LNP023. Vaccination against N. meningitidis type B, S. pneumoniae and H. influenzae should be conducted if available and acceptable by local regulations, at least 30 days prior to first dosing with LNP023
•All patients must have been on supportive care including a maximally tolerated dose of ACEi or ARB therapy for the individual, antihypertensive therapy or diuretics for at least 90 days before dosing
Exclusion criteria
1.Presence of crescent formation in =50% of glomeruli assessed on renal biopsy
2.Patients previously treated with immunosuppressive agents such as cyclophosphamide or mycophenolate mofetil (MMF), or cyclosporine, systemic corticosteroids exposure within 90 days prior to start of LNP023/Placebo dosing
3.Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations
4.All transplanted patients (any organ, including bone marrow)
5.History of immunodeficiency diseases, or a positive HIV (ELISA and Western blot) test result.
Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV). A positive HBV surface antigen (HBsAg) test, or if standard local practice, a positive HBV core antigen test, excludes a patient. Patients with a positive HCV antibody test should have HCV RNA levels measured. Subjects with positive (detectable) HCV RNA should be excluded
6.Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study. The Investigator should make this determination in consideration of the subject's medical history and/or clinical or laboratory evidence of any of the following:
?A history of invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus
?Splenectomy
?Inflammatory bowel disease, peptic ulcers, severe gastrointestinal disorder including rectal bleeding;
?Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
?Pancreatic injury or pancreatitis;
?Liver disease or liver injury as indicated by abnormal liver function tests. ALT (SGPT), AST (SGOT), GGT, alkaline phosphatase and serum bilirubin will be tested.
?Any single parameter of ALT, AST, GGT, alkaline phosphatase or serum bilirubin must not exceed 3 x upper limit of normal (ULN)
?PT/INR must be within the reference range of normal individuals
?Evidence of urinary obstruction or difficulty in voiding any urinary tract disorder other than IgNA that is associated with hematuria at screening and before dosing; [If necessary, laboratory testing may be repeated on one occasion (as soon as possible) prior to randomization, to rule out any laboratory error]
7.Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
8.A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening or baseline:
?PR > 200 msec
?QRS complex > 120 msec
?QTcF > 450 msec (males)
?QTcF > 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
9.History of severe allergic reactions as per Investigator decision
10.Plasma donation (> 200mL) within 30 days prior to first dosing.
11.Donation or loss of 400 mL or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation
12.Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception dur
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method ame: change from baseline of urine protein to creatinine concentration ;Timepoints: Baseline and Day 90 ;Measure: Baseline and Day 90 ;Name: baseline of urine protein to creatinine concentration ratio ;Timepoints: 90 days;Measure: 90 days
- Secondary Outcome Measures
Name Time Method ame: •The effect of LNP023 on renal function - Estimated Glomerular Filtration Rate eGFR ;Timepoints: Baseline, Day 1, 8, 15, 30, 90, 120 ;Measure: Baseline, Day 1, 8, 15, 30, 90, 120 ;Name: •The effect of LNP023 on renal function - Serum creatinine ;Timepoints: Baseline, Day 1, 8, 15, 30, 90, 120 ;Measure: Baseline, Day 1, 8, 15, 30, 90, 120 ;Name: •The effect of LNP023 on renal function - Hematuria ;Timepoints: Baseline, Day 1, 8, 15, 30, 60, 90, 120, 180 ;Measure: Baseline, Day 1, 8, 15, 30, 60, 90, 120, 180 ;Name: •The effect of LNP023 on renal function - 24h-UP, 24h-UA, UACR (urine albumin to creatinine concentration ratio);Timepoints: Baseline, Day 1, 30, 60, 90, 120, 180 ;Measure: Baseline, Day 1, 30, 60, 90, 120, 180