This Phase I study was a randomized, double-blind, placebo-controlled trial in healthy adult volunteers to assess the safety, tolerability, and pharmacokinetics of inhaled ALN-RSV01 administered via nebulizer. All major objectives of the trial were met, including definition of a safe and well-tolerated dose and regimen for advancement of ALN-RSV01 into further Phase II development.
In total, 109 subjects were enrolled in the Phase I trial; 71 were exposed to drug and 38 to placebo. Both single and multiple doses were evaluated, ranging from the equivalent of 0.1 mg/kg to 3 mg/kg in the single dose arm, and 0.01 mg/kg to 0.6 mg/kg, administered once daily for 3 days in the multi-dose arm. Data showed that the efficiency of delivery of ALN-RSV01 delivered via inhalation, as measured by plasma levels, was significantly greater in humans than observed pre-clinically. Adverse events reported for both drug and placebo were predominantly mild; there were no severe or serious adverse events. In the single dose arm, a mild to moderate flu-like adverse event was observed at the higher doses. This was found to be transient and was potentially linked to the enhanced efficiency of delivery. In the multi-dose arm, daily doses up to 0.6 mg/kg for 3 days were found to be safe and well tolerated, pointing to a dose and regimen of ALN-RSV01 for further Phase II evaluation.
Comparison of multi-dose and single dose ALN-RSV01 treatment paradigms demonstrated that a multi-dose regimen (once daily for 3 days) is significantly more efficacious than a single dose, for the same total amount of drug. The company also announced that the Phase II study in experimentally infected adult volunteers is now fully enrolled with 88 subjects and top-line data are expected early in the first quarter of 2008.
Akshay Vaishnaw, vice president, clinical research at Alnylam, said: “These results put us firmly into Phase II development with the ongoing experimental infection study, and now with a planned multi-dose inhalational Phase II strategy in naturally infected adults.”