Study of Safety and Efficacy of LNP023 in Patients With Kidney Disease Caused by Inflammatio
- Conditions
- Health Condition 1: N047- Nephrotic syndrome with diffuse crescentic glomerulonephritis
- Registration Number
- CTRI/2019/11/021978
- 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-specific assessment is
performed.
2. Female and male patients greater than or equal to 18 years of age with a biopsy-verified IgA nephropathy and where the biopsy was performed within the previous three years. If the most recent renal biopsy was performed more than three years ago, a new biopsy should be performed.
3. Able to communicate well with the investigator, to understand and comply with the
requirements of the study.
4. Patients must weigh at least 35 kg to participate in the study, and must have a body mass index within the range of 15 to 38 kg per m2. BMI is equal to Body weight (kg) divided by Height (m)2
5. Measured GFR or estimated GFR calculated using the CKD-EPI formula (or modified
MDRD formula according to specific ethnic groups and local practice guidelines
(Imai et al 2011)) more than or equal to 30 mL per min per 1.73 m2
6. Urine protein to creatinine ratio (UPCR) more than or equal to 0.8 g per g (more than or equal to 90 mg per mmol) sampled from first
morning void (FMV) or urine protein more than or equal to 0.75 g per 24hr from a 24h urine collection at screening and urine protein more than or equal to 0.75 g per 24h from a 24h urine collection at the completion of the run-in period.
7. Vaccination against Neisseria meningitidis types A, C, Y and W-135 is required at least 4
weeks prior to first dosing with LNP023. Vaccination against N. meningitidis type B
should be conducted if available and acceptable by local regulations, at least 4 weeks prior
to first dosing.
8. Vaccination for the prevention of S. pneumoniae and H. influenzae, if available and
acceptable by local regulations, at least 4 weeks prior to first dosing.
9. 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.
10. Laboratory values must meet the following criteria:
hemoglobin more than or equal to 9.0 g per dL
platelet count more than or equal to 100,000 per mm3.
11. Vital signs should be within the following ranges
body temperature between 35.0 to 37.5 °C
systolic blood pressure 90 to 160 mm Hg
diastolic blood pressure 50 to 90 mm Hg
pulse rate 40 to 90bpm, below 50bpm if no other clinically significant ECG abnormalities as
per Investigator decision. For subjects with heart rates less than 50 bpm, evidence should
be provided that they have no history of
(i) moderate or severe valvular disease
(ii) history of coronary artery disease, myocardial infarction, hypertension or diabetes
mellitus
(iii) history of cardiomyopathy, congenital heart defect, open heart surgery, or
ongoing arrhythmia
(iv) family history of sudden death in a first degree relative.
1. Presence of crescent formation in more than or equal to 50 percent of glomeruli assessed on renal biopsy.
2. Patients previously treated with immunosuppressive agents such as cyclophosphamide, mycophenolate mofetil (MMF) or mycophenolate sodium, cyclosporine, tacrolimus,
sirolimus or systemic corticosteroids exposure within 90 days prior to start of
LNP023 or Placebo dosing.
3. Patients who previously have received LNP023. 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 subjectâ??s medical history and/or clinical or laboratory evidence of any
of the following:
i.A history of invasive infections caused by encapsulated organisms, e.g.
meningococcus or pneumococcus
ii.Splenectomy
iii.Inflammatory bowel disease, peptic ulcers, severe gastrointestinal disorder including
rectal bleeding
iv.Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel
resection
v.Pancreatic injury or pancreatitis;
vi.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.
vii.Any single parameter of ALT, AST, GGT, alkaline phosphatase or serum bilirubin
must not exceed 2 x upper limit of normal (ULN)
viii.PT/INR must be within the reference range of normal individuals
ix.Evidence of urinary obstruction or difficulty in voiding any urinary tract disorder
other than IgAN 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:
a.PR more than 200 msec
b.QRS complex more than 120 msec
c.QTcF more than 450 msec (males)
d.QTcF more than 460 msec (females)
e.History of familial long QT syndrome or known family history of Torsades de Pointes
f.Use of agents known to prolong the QT interval unless th
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1.Change from baseline of urine protein to creatinine concentration <br/ ><br>2.Baseline of urine protein to creatinine concentration ratioTimepoint: 1.Baseline and Day 90 <br/ ><br>2.UPCR based on 24h urine collection at 90 days
- Secondary Outcome Measures
Name Time Method