Browse the corpus

Favipiravir for Lassa fever: an open-label, randomized controlled phase 2 trial. Lassa fever (LF) is a viral hemorrhagic fever endemic to West Africa, with high case fatality in hospitalized patients and limited treatment options, including ribavirin. Preclinical evidence suggests high-dose favipiravir is a promising antiviral treatment alternative. We conducted a randomized controlled open-label phase 2 clinical trial at two reference hospitals in Nigeria to evaluate favipiravir in the treatment of LF. Primary endpoints were the description of classic pharmacokinetic parameters (maximum plasma concentration, time to reach maximum plasma concentration, area under the curve (AUC), half-life and volume of distribution) as well as the safety and tolerability of favipiravir compared with ribavirin in the treatment of acute LF. Hospitalized adult patients with mild-to-moderate RT-PCR-confirmed LF were eligible to participate. In total, 41 patients were randomized (ribavirin n = 21; favipiravir n = 20), and 36 completed the 10-day follow-up period. A total of 19 (46.3%) participants were female, and the median age was 37 years. The primary endpoints were met. Pharmacokinetic analysis of favipiravir in a one-compartment model indicated reliable exposure with maximum plasma concentration of 50.9 (IQR 42.1 to 75.1) mg l-1 in steady state, half-life of 10.9 (IQR 8.2 to 17.1) h and AUC (0-240 h) of 9,275 (IQR 7,139.4 to 15,794.8) mg l-1 h-1. The 30 drug-related treatment-emergent adverse events were evenly distributed between the treatment arms; 16 (53.5%) events occurred in the favipiravir group, and none of these were classified as severe or serious. Anemia was the most frequently observed adverse event in the ribavirin arm and vomiting in the favipiravir arm. All study participants survived and were successfully discharged from the isolation ward. This trial indicates favipiravir's potential as a safe and well-tolerated alternative treatment regimen for LF and pharmacokinetic data suggest an optimized favipiravir regimen for future clinical evaluation. Clinicaltrials.gov: NCT04907682 .