A Study to Investigate Safety and Effect of Sparsentan in Combination With SGLT2 Inhibition in Participants With IgAN

Study Overview
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Brief Summary
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This is a 28-week, open-label, multicenter, single-group Phase 2 exploratory study to determine the safety and effect of sparsentan in participants with IgAN who are at risk of disease progression to kidney failure despite being on both stable RAASi and SGLT2 inhibitor treatment for at least 12 weeks prior to study entry

Detailed Description
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This is a 28-week, open-label, multicenter, single-group Phase 2 exploratory study to determine the safety and effect of sparsentan in participants with Immunoglobulin A Nephropathy (IgAN) who are at risk of disease progression to kidney failure (KF) despite being on both stable renin angiotensin aldosterone system inhibitor (RAASi) and sodium glucose cotransporter-2 (SGLT2) inhibitor treatment for at least 12 weeks prior to study entry. Participants who provide written informed consent will be assessed for eligibility and will undergo baseline evaluations including clinical laboratory tests. Per the eligibility criteria, all participants are required to be on a stable dose(s) of angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) and on a stable dose of a SGLT2 inhibitor at screening and will continue their stable treatments through the screening period. Eligible participants will discontinue ACEI and/or ARB therapy the day before the Day 1 visit and remain on stable SGLT2 inhibitor dosing for the duration of the study. Study intervention will be administered daily for a treatment period of 24 weeks with study visits conducted at weeks 2-, 4-, 12-, and 24- following Day 1. Following the 24-week treatment period, study intervention will be discontinued for 4 weeks and standard of care RAASi treatment resumed, with a safety visit at Week 28.

Official Title
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A Multicentered, Single-group Phase 2, Exploratory, Open-label Study to Investigate Safety and Effect of Sparsentan in Combination With SGLT2 Inhibition in the Treatment of Adult Participants With IgAN

Conditions
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Immunoglobulin A Nephropathy

Intervention / Treatment
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* Drug: Sparsentan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥18 years at the time of signing the informed consent. Biopsy-proven IgAN. The biopsy may have been performed at any time in the past. UA/C ≥0.3 g/g at screening An eGFR value of ≥25 mL/min/1.73m2 at screening. On a stable dose of an SGLT2 inhibitor for at least 12 weeks prior to screening. On a stable dose of ACEI and/or ARB therapy for at least 12 weeks prior to screening that is: The participant's maximum tolerated dose (MTD), and at least one half of the maximum labeled dose (MLD) Exclusion Criteria: IgAN secondary to another condition or immunoglobulin A (IgA) vasculitis. Undergone any organ transplant, with the exception of corneal transplants. Documented history of heart failure, clinically significant cardiovascular or liver disease. Taking high dose (defined as >10 mg/day prednisone) or other any systemic immunosuppressive medications within 12 weeks of prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sparsentan<br>Sparsentan will be administered daily as a 200-mg oral tablet. The goal is to titrate from the initial dose of 200 mg (Day 1) to the target dose of 400 mg at Week 2. | Drug: Sparsentan<br>* Target dose of 400 mg daily<br>* Other names: RE-021;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urine albumin-creatinine ratio (UA/C) at Week 24 | The change from baseline in UA/C at Week 24 based on first morning void (FMV) samples | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UA/C <0.2 g/g at Week 24 | Achievement of UA/C of <0.2 g/g at Week 24 based on FMV samples | Week 24 | 
| 30% and 50% reduction from baseline in UA/C at Week 24 | Achievement of 30% and 50% reduction from baseline in UA/C at Week 24 based on FMV samples | Week 24 | 
| UA/C and Urine protein-to-creatinine ratio (UP/C) at each visit | Change from baseline in UA/C and UP/C at each visit based on FMV samples | Week 24 | 
| Estimated glomerular filtration rate (eGFR) at each visit | Change from baseline eGFR at each visit | Week 24 | 
| Blood pressure (BP) at each visit | Change from baseline systolic and diastolic BP at each visit. | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgAN