Study Design and Baseline Characteristics of ALIGN, a Randomized Controlled Study of Atrasentan in Patients With IgA Nephropathy
Hiddo J.L. Heerspink, Meg Jardine, Donald E. Kohan, Richard Lafayette, Adeera Levin, Adrian Liew, Hong Zhang, Irene de Lourdes Noronha, Hernán Trimarchi, Fan Fan Hou, Ronny Renfurm, Todd Gray, Marianne Camargo, Jonathan Barratt
Abstract
Introduction Endothelin A (ET A ) receptor activation is a driver of proteinuria, kidney inflammation and fibrosis in IgA nephropathy (IgAN). Atrasentan, a selective ET A receptor antagonist, has potential to reduce proteinuria and preserve kidney function in IgAN. ALIGN (NCT04573478) is a phase 3, randomized, double-blind, placebo-controlled clinical trial of atrasentan in patients with IgAN at high risk of kidney function loss. Methods Eligibility criteria for the ALIGN main stratum included patients with biopsy-proven IgAN, total protein excretion ≥1g/d, eGFR ≥30 mL/min/1.73m 2 , receiving a maximally-tolerated stable dose of a renin-angiotensin system inhibitor (RASi). An exploratory stratum enrolled participants also receiving a stable dose of sodium glucose cotransporter-2 inhibitors (SGLT2i). Participants were randomized to 0.75 mg atrasentan or placebo orally daily for 132 weeks followed by a 4-week wash-out period. The primary outcome is proteinuria change from baseline (24h urine protein–creatinine ratio UPCR) to Week 36 in the main stratum. Key secondary endpoints include eGFR change from baseline to Week 136, safety and tolerability. Results Enrolment occurred across 20 countries; 404 patients are randomized: 340 in the main stratum and 64 in the SGLT2i stratum. At baseline in the main stratum, mean age was 44.7 years, 42.4% were female, mean eGFR and median UPCR were 58.9 mL/min/1.73 m 2 and 1.4 g/g, respectively. Conclusion The ongoing ALIGN trial evaluates the efficacy and safety of atrasentan in a representative global IgAN population at risk for disease progression despite optimized RASi therapy and includes an exploratory stratum evaluating atrasentan use in combination with an SGLT2i.