Primary immunoglobulin A nephropathy (IgAN)
Conditions
Interventions
Cohort 1 (12 to < 18 years of age): Iptacopan 200 mg b.i.d.(twice daily)
Cohort 2 (2 to < 12 years old): Dosing tbd
Sponsors
Maruyama Hideki
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female participants 2 to = 30 mL/min/1.73m2 where eGFR is calculated using the modified Schwartz formula at Screening and confirmed during the Run-in Period. 3. Kidney biopsy-proven primary IgAN*, with biopsy performed within 3 years of Screening with = 1 g/g (113 mg/mmoL) sampled from FMV at Screening on Day -90 and Day -60 as well as during the Run-in Period despite treatment with maximum tolerated dose of ACE inhibitor/ARB for at least 120 days prior to Day 1. Note: UPCR will be assessed based on one FMV sample at Day -90 and based on the geometric mean of 2 FMV samples for the Day -60 visit and during the Run-in Period. 6. Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, vaccine should be given according to local guidelines at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated. 7. Vaccination against Haemophilus influenzae is recommended, according to local guidelines, at least 2 weeks before iptacopan. 8. All participants must have been on supportive care including stable dose regimen of ACE inhibitor or ARB at either the locally approved maximal daily dose per body weight, or the maximally tolerated dose (per Investigator's judgment for pediatric use), for at least 120 days before first study drug administration. In addition, if participants are taking diuretics, other antihypertensive medication, or other background medication for IgAN (such as SGLT2 inhibitors), the doses should also be stabilized for at least 120 days prior to the first dosing of study treatment.
Exclusion criteria
Exclusion criteria: 1. Any secondary IgAN observed at Screening (and confirmed at Baseline/Day 1) as defined by the Investigator; secondary IgAN can be associated with cirrhosis, celiac disease, human immunodeficiency virus (HIV) infection, herpes simplex virus infection, dermatitis herpetiformis, seronegative arthritis, small-cell carcinoma, lymphoma, disseminated tuberculosis, bronchiolitis obliterans, inflammatory bowel disease, and familial mediterranean fever. 2. A clinical diagnosis of immunoglobulin A vasculitis (IgAV or Henoch-Schonlein purpura) at Screening (and confirmed at Baseline/Day 1) based on typical palpable purpura with or without arthralgia and abdominal pain. 3. Evidence of significant urinary obstruction or difficulty in voiding at Screening (and confirmed at Baseline/Day 1); any urinary tract disorder or any chronic kidney disease other than IgAN at Screening and before first study drug administration. 4. Current acute kidney injury (AKI) defined by Acute Kidney Injury Network (AKIN) criteria within 4 weeks of screening. 5. Presence of rapidly progressive glomerulonephritis (RPGN) as defined by 50% decline in eGFR within 3 months prior to Screening or during the Screening and Run-in periods. 6. Presence of nephrotic syndrome at Screening based on the investigator's judgment. 7. History or current diagnosis of ECG abnormalities indicating significant risk for study participants such clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, or clinically significant second- or third-degree atrioventricular (AV) block without a pacemaker. 8. History or current diagnosis of clinically significant echocardiogram abnormalities indicating significant risk for study participants including but not limited to clinically significant functional, morphological and/or structural abnormalities, which may include left ventricular ejection fraction 150 mmHg, or diastolic blood pressure (DBP) 95 mmHg, or pulse rate 110 bpm; participants of 6 to 140 mmHg, or DBP 90 mmHg or pulse rate 156 bpm; participants of 2 to 120 mmHg, or DBP 80 mmHg or pulse rate 156 bpm at Screening. 10. Participants previously treated with immunosuppressive or other immunomodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), calcineurin inhibitors, complement inhibitors (other than iptacopan), oral budesonide, systemic corticosteroids exposure (>= 0.5 mg/kg/day of prednisone/prednisolone equivalent or > 7.5 mg/d prednisone/prednisolone equivalent total exposure in a single day) within 120 days (or 180 days for rituximab) prior to first study drug administration. Participants treated with endothelin (receptor) antagonists (including sparsentan) within 120 days prior to first study drug administration. Use of other investigational drugs within 5 half-lives of Day 1, or within 30 days, whichever is longer. 11. All transplanted participants (any solid organ transplantation, including bone marrow transplantation). 12. History of recurrent invasive infections caused by encapsulated organisms, such as meningococ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Log-transformed ratio to Baseline in UPCR (based on FMV) Timeframe: baseline, Week38 | — |
Countries
Japan, United States
Contacts
Public ContactHideki Maruyama
Novartis Pharma. K.K.
Outcome results
None listed