Evaluation of Rusfertide, a Hepcidin Mimetic, on Cardiac Repolarization: A Randomized, Placebo- and Positive-Controlled Crossover Thorough QT Study in Healthy Participants
Abstract
PURPOSE: Rusfertide, a hepcidin mimetic, is in clinical development for the treatment of polycythemia vera. This study evaluated the effect of rusfertide on cardiac repolarization.
METHODS: A positive-controlled, randomized, double-blind, crossover study was conducted in healthy adults. Subjects received subcutaneous rusfertide 90 mg, matching subcutaneous placebo, and oral moxifloxacin. Subjects underwent continuous 12-lead Holter recording during each period. A central laboratory extracted up to 10 replicate electrocardiograms (ECGs) at each time point prior to and following treatment, paired with pharmacokinetic sampling. The primary analysis for Fridericia corrected QT interval (QTcF) was a mixed model for repeated measures with change from baseline QTcF (ΔQTcF) as the dependent variable; period, sequence, time, treatment, and time-by-treatment interaction as fixed effects; and baseline QTcF as a covariate. The relationship between rusfertide and metabolite concentrations and change-from-baseline QTcF was quantified using linear mixed-effects modeling.
FINDINGS: Mean age and body mass index were 40.1 years and 25.4 mg/m2, respectively, with a slight majority of female (57%) and White (60%) subjects. Mean rusfertide plasma concentrations increased rapidly, with median peak of 4 hours. The geometric mean rusfertide peak concentration (Cmax) was 1100 ng/mL. Rusfertide did not have a clinically relevant effect on heart rate (HR) or cardiac conduction (PR and QRS interval).…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 24 participants or records.
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