A Study of the Effect and Safety of Sparsentan in the Treatment of Patients With IgA Nephropathy (PROTECT)
Immunoglobulin A Nephropathy
About this trial
This is an interventional treatment trial for Immunoglobulin A Nephropathy
Eligibility Criteria
Key Inclusion Criteria for the Double-Blind Period:
- Age 18 years or older at screening
- Biopsy-proven primary IgAN
- Proteinuria of ≥1 g/day at screening
- eGFR ≥30 mL/min/1.73 m2 at screening
- Currently on stable dose of ACEI and/or ARB therapy, for at least 12 weeks prior to screening (maximum tolerated dose and at least one-half of the maximum labeled dose)
- Systolic BP ≤150 mmHg and diastolic BP ≤100 mmHg at screening
- Willing to undergo change in ACEI and/or ARB and anti-hypertensive medications
- Agree to contraception
Key Exclusion Criteria for the Double-Blind Period:
- IgAN secondary to another condition
- Presence of cellular glomerular crescents in >25% of glomeruli on renal biopsy (if biopsy available within 6 months of screening)
- Chronic kidney disease (CKD) in addition to IgAN
- History of organ transplantation, with exception of corneal transplants
- Require any prohibited medications
- Treatment of systemic immunosuppressive medications (including corticosteroids) for >2 weeks within 3 months of screening
- History of heart failure or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema
- Clinically significant cerebrovascular disease or coronary artery disease within 6 months of screening
- Jaundice, hepatitis, or known hepatobiliary disease or elevations of transaminases (ALT/AST) >2 times upper limit of normal at screening
- History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years
- Hematocrit value <27% (0.27 V/V) or hemoglobin value <9 g/dL (90 g/L) at Screening
- Potassium >5.5 mEq/L (5.5 mmol/L) at Screening
- History of alcohol of illicit drug use disorder
- History of serious side effect or allergic response to any angiotensin II antagonist or endothelin receptor antagonist, including sparsentan or irbesartan, or has a hypersensitivity to any of the excipients in the study medications
- For female: Pregnancy, or planning to become pregnant during the course of the study, or breastfeeding
- Participation in a study of another investigational product within 28 days of screening
Key Inclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 visit:
- Completed participation in the double-blind period, including the Week 114 visit
- Did not permanently discontinue study medication during the double-blind period
- Agree to contraception
Key Exclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 and Week 114 visits:
- Progression to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT)
- Development of any criteria for discontinuation of study medication or discontinuation from the study, between Week 110 and Week 114
- Patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 110 and Week 114
- eGFR ≤20 mL/min/1.73 m2 at Week 110
- Female patient is pregnant or breastfeeding
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Active Comparator
Experimental
Experimental
sparsentan
irbesartan
dapagliflozin + sparsentan (Sub study)
sparsentan (Sub Study)
Double-blind: Sparsentan will be administered daily as a 200-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 200 mg after 2 weeks will increase their dose to 400- mg and continue treatment to Week 110.
Double-blind: Irbesartan will be administered daily as a 150-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 150 mg after 2 weeks will increase their dose to 300 mg and continue treatment to Week 110.
OLE Sub study: Dapagliflozin will be administered daily as a 5-mg oral tablet, in addition to 400-mg of Sparsentan, for a period of 12 weeks.
OLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks.