To determine the nephroprotective potential of treatment with sparsentan in patients newly-diagnosed with immunoglobulin A nephropathy (IgAN) (ie, incident patients) who have not received prior angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy.
A multi-centre, open-label, single-group trial is proposed to explore the safety of, and response to sparsentan treatment in incident, renin angiotensin system (RAS) blockade-naïve patients with biopsy-proven immunoglobulin A nephropathy (IgAN). The purpose is to explore sparsentan treatment as a potential first-line treatment in patients newly diagnosed with IgAN (ie, incident patients), who have thus not received prior treatment with ACEI or ARB therapy for IgAN. Response to treatment will be assessed as changes from baseline rather than comparison to another treatment, and will be based on established proteinuria endpoints (UPCR and protein excretion), and glomerular filtration rate (GFR); a number of exploratory measures will be assessed as well. The starting dose of sparsentan will be 200 mg/day, which will be titrated up to the target dose of 400 mg/day at Week 2. Patients who do not tolerate the target dose will have their dose reduced back to 200 or 100 mg/day; throughout the study, patients will be maintained on the maximum allowed dose of sparsentan they can tolerate. All patients will be treated with sparsentan for a total of 110 weeks, followed by an off-treatment follow-up period of 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Target dose of 400 mg daily
Cambridge University Hospitals NHS Trust
Cambridge, England, United Kingdom
Northern Care Alliance NHS Foundation Trust - Salford Royal
Salford, England, United Kingdom
Royal Infirmary of Edinburgh & Western General Hospital
Edinburgh, Scotland, United Kingdom
University Hospital of wales
Cardiff, Wales, United Kingdom
Leicester General Hospital, University Hospitals of Leicester NHS Trust
Leicester, United Kingdom
Urine protein/creatinine ratio (UP/C) at Week 36
The primary efficacy endpoint is the change from baseline in the urine protein/creatinine ratio (UP/C), based on a 24-hour urine sample, at Week 36.
Time frame: Week 36
eGFR over a 52-week period
Rate of change in eGFR over a 1-year (52 week) period following the initial acute effect of therapy (ie, from 6 weeks post-initiation of investigational medicinal product (IMP) to 58 weeks post-initiation of IMP).
Time frame: Week 58
eGFR over a 104-week period
Rate of change in eGFR over a 2-year (104 week) period following the initial acute effect of therapy (ie, from 6 weeks post-initiation of investigational medicinal product (IMP) to 110 weeks post-initiation of IMP).
Time frame: Week 110
Change from baseline in proteinuria
Change from baseline in proteinuria, measured by urinary protein/creatinine ratio \[UPCR\] and 24-hour protein excretion, up to Week 114
Time frame: Up to Week 114
Abnormalities in clinical laboratory assessments and vital signs
Proportion of patients with abnormalities in clinical laboratory assessments and vital signs at each visit
Time frame: Up to Week 114
Incidence of adverse events (AEs), serious AEs, AEs leading to discontinuation, AEs leading to death
AEs, serious AEs, AEs leading to discontinuation, AEs leading to death
Time frame: Up to Week 114
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