Arca biopharma has provided an update on GENETIC-AF, the company’s phase 2B/3 clinical trial evaluating Gencaro (bucindolol hydrochloride) as a potential treatment for atrial fibrillation. ARCA has identified common genetic variations that it believes may predict individual patient response to Gencaro, giving it the potential to be the first genetically-targeted atrial fibrillation prevention treatment.
The multicentre, randomised, double-blind clinical trial is comparing the safety and efficacy of Gencaro to Toprol-XL (metoprolol succinate) for the treatment of atrial fibrillation in patients with heart failure and left ventricular systolic dysfunction (HFREF patients). The primary endpoint of GENETIC-AF is time to symptomatic atrial fibrillation /atrial flutter. Arca is enrolling only HFREF patients with the genetic variant of the cardiac beta-1 adrenergic receptor, which the company believes responds most favourably to Gencaro, the 389 arginine homozygous genotype.
GENETIC-AF has an adaptive design, under which the company initiated the trial as a phase 2B trial seeking to enrol approximately 200 patients. The GENETIC-AF Data Safety Monitoring Board will analyse certain data from the phase 2B portion of the trial and recommend, based on a comparison to the pre-trial statistical assumptions, whether the trial should proceed to phase 3 and seek to enrol an additional 420 patients.
There are currently 38 active clinical trial sites in the USA and Canada. The company anticipates that approximately 65 sites will be activated for the phase 2B portion of GENETIC-AF. Trial enrolment has not met the company’s original projections, with the trial having screened 37 patients who met the general clinical inclusion criteria and signed informed consent for genotyping, resulting in 12 patients who were randomised into the trial. The percentage of screened patients who have the targeted genotype is consistent with pre-trial assumptions of approximately 50%. The company believes the original trial eligibility criteria overly restricted the potential pool of appropriate patients for the trial and contributed to the number of screened patients who subsequently became ineligible for randomisation.
To address these issues, Arca has implemented amendments to the trial protocol that it believes may expand the eligible target population, increase the patient screening and enrolment rate, and simplify trial procedures.
Under the revised protocol, patients in sinus rhythm who have experienced symptomatic atrial fibrillation in the past 120 days are now eligible for inclusion in the trial, as are patients with atrial fibrillation episodes lasting seven days or fewer (ie. paroxysmal atrial fibrillation).
Arca says that the amendments to the protocol do not fundamentally alter or impact the original endpoints of the clinical trial. The company now anticipates that the enrolment of 200 patients for the phase 2B portion of the trial may be completed by the end of 2016. Arca anticipates the first trial sites to be approved, trained and operating under the revised protocol in June 2015.
The company has met with the US Food and Drug Administration to confirm the acceptability of the amendments to the protocol and received no objections.