An Arrowhead Research official this week denied reports that concerns over potency or toxicity have prompted the company to expand a phase I trial of its investigational hepatitis B treatment ARC-520, which has just moved into phase IIa testing.
According to Vince Anzalone, vice president of finance at Arrowhead, "regulators did not ask us to go back to dose more healthy volunteers and there were no safety signals of concern" in the phase I study.
Rather, Arrowhead is keeping the study open in order to "maintain the maximum amount of flexibility should there be value in adding cohorts," he told Gene Silencing News.
The phase I trial was designed to test single doses of ARC-520 ranging from 0.01 mg/kg up to 2 mg/kg in healthy volunteers. In late 2013, Arrowhead presented data from that study showing that the drug was safe and well tolerated, with no serious adverse events or dose-limiting toxicities observed.
There were some minor to moderate adverse events, but the frequency of these did not vary between treatment and placebo groups.
On these data, Arrowhead moved forward with a planned multi-dose phase IIa study in HBV-infected patients in Hong Kong.
Anzalone noted that the phase I study originally listed an expected enrollment figure of 44 individuals on the clinicaltrials.gov website, with the extra volunteers included to account for potential dropouts or discontinuations. Earlier this year, however, that number was increased to 48.
A handful of investors and analysts picked up on the change, he explained, and began speculating that Arrowhead was adding patients to the phase I trial in order to address potential problems with ARC-520.
He said that this speculation is incorrect and that the enrollment figure was increased just in case "we see some value in adding cohorts."
He declined to comment specifically on whether volunteers beyond the original 36 had been dosed in the phase I study, but confirmed that no one has been treated with a dose higher than the 2 mg/kg maximum dose reported on last year.
The phase IIa trial is testing 1 mg/kg and 2 mg/kg doses of ARC-520, which Anzalone said is believed to be the drug's therapeutic range.
He added that should Arrowhead decide to test higher doses of the drug, it would likely do so in the phase IIa via a protocol amendment. Going beyond 2 mg/kg, he said, "shouldn't require us to go back to healthy volunteers," he said, citing discussions with regulators and study investigators.
However, if that is not the case and healthy volunteer data at the potentially higher dose is required, keeping the phase I open gives Arrowhead the ability to do so in a timely manner, he noted.
Anzalone said that Arrowhead considers the phase I trial completed, but that enrollment would likely remain open while the phase IIa is conducted. The company expects to complete the newest study in the second quarter, with data available in the third quarter.