Arca Biopharma has announced an update on the GENETIC-AF trial, which will evaluate bucindolol (Gencaro) as a potential treatment for atrial fibrillation.
Michael Bristow, Arca’s president and chief executive officer comments, “In the ongoing GENETIC-AF clinical trial, we are evaluating bucindolol as potentially the first genetically-targeted treatment for atrial fibrillation. We believe we are on track to enrol sufficient patients by year-end for the Data Safety Monitoring Board (DSMB) to begin the pre-specified interim analysis with the outcome of the analysis anticipated in the first half of 2017.”
The GENETIC-AF is a phase 2B/phase 3, multicentre, randomised, double-blind, adaptive design clinical trial comparing the safety and efficacy of bucindolol to metoprolol succinate (Toprol-XL) for the treatment of atrial fibrillation (AF) in a combined total of approximately 620 patients.
Eligible patients will have heart failure with reduced left ventricular ejection fraction (HFREF), have a history of paroxysmal AF (episodes lasting seven days or less) or persistent AF (episodes lasting more than seven days and less than one year) in the past six months, and have the beta-1 389 arginine homozygous genotype which Arca believes responds most favourably to bucindolol.
The primary endpoint of the study is time to first event of symptomatic AF/atrial flutter (AFL) or all-cause mortality. The combined phase 2B/phase 3 trial is designed for 90% power at a p-value of less than 0.01 significance level to detect a 25% reduction in the primary endpoint for patients in the bucindolol arm compared to patients in the metoprolol succinate arm. The trial is currently enrolling patients in the USA and Canada.
The GENETIC-AF DSMB will conduct a pre-specified interim analysis of study endpoints for efficacy, safety and futility to recommend whether the trial should proceed to phase 3. The DSMB will make its recommendation based on a predictive probability analysis of certain trial data after at least 150 patients have evaluable endpoint data.
An enrolled patient has evaluable endpoint data either when they experience their first endpoint event, or after they complete the 24-week follow up period. The DSMB interim analysis will focus on analyses of the AF/AFL endpoints in the trial using both clinical-based intermittent monitoring and device-based continuous monitoring techniques. Should the DSMB interim analysis indicate that the data are consistent with pre-trial statistical assumptions and the potential for achieving statistical significance for the phase 3 endpoint, the DSMB may recommend that the study proceed to phase 3. The DSMB may also halt the study for futility.
Based on the current enrolment rate, Arca expects to enrol at least 150 patients by the end of 2016. The Company expects the outcome of the DSMB interim analysis and recommendation regarding the potential transition to phase 3 in the first half of 2017.
In February 2016, the GENETIC-AF protocol was amended to simplify certain operational aspects of the trial. The company believes these modifications will facilitate site recruitment and enrolment in existing trial sites and potential sites in European countries, where the company anticipates expanding the study to support both the later portion of phase 2B, as well as the potential phase 3 portion of the trial. The company believes inclusion of European investigative sites may support potential European regulatory submissions and partnering discussions. Arca received no objection from the US Food and Drug Administration.