IMPROVE-DiCE, a 2-Part, Open-Label, Phase 2a Trial Evaluating the Safety and Effectiveness of Ninerafaxstat in Patients With Cardiometabolic Syndromes

BACKGROUND: We report IMPROVE-DiCE (Improve Diabetic Cardiac Energetics), a 2-part open-label, phase 2a trial evaluating the safety and effectiveness of ninerafaxstat, a novel therapeutic designed to enhance cardiac energetics. Between May and September 2021, part 1 enrolled patients with type 2 diabetes and obesity without heart failure with preserved ejection fraction (HFpEF). Between January 2023 and June 2024, part 2 enrolled patients with type 2 diabetes, obesity, and HFpEF. METHODS: C]pyruvate magnetic resonance spectroscopy to assess in vivo pyruvate dehydrogenase flux (n=9) and plasma metabolomics and proteomics were also performed. RESULTS: =0.02), and improved New York Heart Association class symptom burden. CONCLUSIONS: These mechanistic phase 2a study results show that ninerafaxstat is safely tolerated and improves myocardial energetics in participants with obesity and diabetes without or with clinically manifest HFpEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04826159.