The ASSIST study was a phase 2, double-blind, placebo-controlled crossover study to evaluate the safety and efficacy of atrasentan vs. placebo in subjects with IgA nephropathy (IgAN) while on background standard of care therapy and an SGLT2 inhibitor (SGLT2i).
Patients with biopsy-proven IgAN who were on a background SGLT2i and a maximally tolerated and stable dose of a renin-angiotensin system inhibitor (RASi) \[such as angiotensin converting enzyme inhibitor (ACEi) or angiotensin-receptor antagonist (ARB)\] as part of standard of care, were randomized to either sequence Atrasentan/Placebo or sequence Placebo/Atrasentan in which they received 0.75 mg atrasentan once daily during one period (period A), complete a 12-week washout period, and then received matching placebo during the other period (period B) as determined by the randomization schema. Subjects who were not on background SGLT2i therapy would first undergo a run-in period of 8 weeks with an SGLT2i with a 24-hour total urine protein of \> 0.85 grams/day at screening prior to the run-in period and have 24-hour total urine protein of \> 0.5 grams/day at the end of the run-in period to be eligible for randomization. Subjects remained on their maximally tolerated and stable dose of RASi and stable dose of SGLT2i therapies for the duration of the study following randomization. The primary objective of the study was to evaluate the efficacy of atrasentan vs. placebo while on background therapy with SGLT2i.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
54
Period A (12 Weeks) - Film-coated tablet, Washout Period: 12 weeks, Period B (24 Weeks) - Placebo
Period B (12 Weeks) - Placebo, Washout Period: 12 weeks, Period A (24 Weeks) - Film-coated tablet
Placebo
Percentage Change in Proteinuria (UPCR From a 24-Hour Urine Collection) From Baseline to Week 12
Change in proteinuria from Baseline to Week 12 across both periods between atrasentan versus placebo. Proteinuria was assessed using the urine protein to creatinine ratio (UPCR) measured from a 24-hour urine collection.
Time frame: From Baseline to Week 12
Percentage Change in Proteinuria (UPCR From a 24-Hour Urine Collection) From Baseline to Week 24 in Treatment Period 2.
Change in proteinuria from Baseline to Week 24 in Treatment Period 2 between atrasentan versus placebo. Proteinuria was assessed using the urine protein to creatinine ratio (UPCR) measured from a 24-hour urine collection.
Time frame: From Baseline to Week 24 of Treatment Period 2
Number of Subjects With TEAE and TEAESI
Number of Subjects With Treatment-Emergent Adverse Events (TEAE) and Treatment-Emergent Adverse Events of Special Interest (TEAESI). Severity assessment of AEs was based on CTCAE (Common Terminology Criteria for Adverse Events).
Time frame: From first dose of study treatment until end of study, up to 60 weeks
Plasma Concentration of Atrasentan
Blood samples were collected for the measurement of plasma concentrations of atrasentan.
Time frame: Treatment Period 1: Pre-dose on Weeks 2, 6 and 12; Treatment Period 2: Pre-dose on Weeks 2, 6, 12 and 24
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