Phase 2b trial of an oral relaxin family peptide receptor 1 agonist in patients with chronic heart failure: rationale and design

INTRODUCTION: AZD5462 is the first oral relaxin family peptide receptor 1 agonist in clinical development and is expected to reduce systemic vascular resistance and afterload and to increase natriuresis, decreasing circulating blood volume, benefitting patients with chronic heart failure (HF). LUMINARA is a Phase 2b study of the efficacy and safety of AZD5462 in participants with broad HF. STUDY DESIGN: This randomized, placebo-controlled, double-blind, multi-centre, dose-ranging study will include ∼360 participants with HF: 220 with left ventricular ejection fraction (LVEF) ≤35% (Cohort A) and 140 with LVEF 41%-55% (Cohort B) will be randomized 1:1:1:1 to three once daily oral doses of AZD5462 or placebo for 24 weeks. Primary endpoints are changes in end-systolic volume index (Cohort A) and systemic vascular resistance index (Cohort B) after 24 weeks. Secondary endpoints include changes in echocardiographic parameters, health status, cardiorenal biomarkers and pharmacokinetics. The safety of AZD5462 will be monitored throughout the study. DISCUSSION: This study will evaluate AZD5462 as a novel oral therapy for patients with chronic HF, aiming to improve symptoms as well as haemodynamic and cardiorenal biomarkers. The findings may provide insights on the development of AZD5462 in a future Phase 3 trial.