Imara has modified the primary goal of the Phase IIb Ardent clinical trial of tovinontrine (IMR-687) in individuals with sickle cell disease (SCD), a rare red blood cell disorder.
The move comes after the US Food and Drug Administration (FDA) provided a written recommendation to change the primary endpoint.
Tovinontrine is a small molecule inhibitor of phosphodiesterase-9 (PDE9).
The international, randomised, placebo-controlled, double-blind, multicentre trial has concluded the target enrolment of nearly 115 adult subjects with SCD, who will receive either tovinontrine or a placebo.
Imara had sought FDA feedback on the draft statistical analysis plan (SAP) for the trial where fetal haemoglobin (HbF) response was the primary goal while the key secondary goal was the annualised rate of vaso-occlusive crises (VOCs).
The FDA subsequently suggested Imara update the primary goal to an annualised rate of VOCs.
Imara noted that HbF response will now become the crucial secondary goal of the trial while its conduct or operational components are unaffected by the endpoint modifications.
Assessment of the impact of tovinontrine against placebo on various VOC-linked outcome measures, markers of red blood cell hemolysis, HbF-related biomarkers, quality of life measures and white blood cell adhesion markers for a year will be the other goals of the trial.
An interim assessment of VOC rates is anticipated to be carried out in the first quarter while final data analysis will be conducted in the second quarter of next year.
Imara president and CEO Rahul Ballal said: “A reduction in VOC rate is an established approval endpoint, and we are engaging the FDA further on this and related topics, including possible streamlined paths to registration.”
“The first review of data from the Ardent trial, including annualized VOC rate, will be conducted when all subjects have completed an assessment at Week 24 or terminated early and are planned for the first quarter of 2022, subject to our upcoming discussions with the FDA.”