Emodepside for <i>Trichuris trichiura</i> and Hookworm Infection.

Abstract

Current treatments for soil-transmitted helminth infections in humans have low efficacy against <i>Trichuris trichiura</i>. Emodepside - a drug in veterinary use and under development for the treatment of onchocerciasis in humans - is a leading therapeutic candidate for soil-transmitted helminth infection. We conducted two phase 2a, dose-ranging, randomized, controlled trials to evaluate the efficacy and safety of emodepside against <i>T. trichiura</i> and hookworm infections. We randomly assigned, in equal numbers, adults 18 to 45 years of age in whom <i>T. trichiura</i> or hookworm eggs had been detected in stool samples to receive emodepside, at a single oral dose of 5, 10, 15, 20, 25, or 30 mg; albendazole, at a single oral dose of 400 mg; or placebo. The primary outcome was the percentage of participants who were cured of <i>T. trichiura</i> or hookworm infection (the cure rate) with emodepside 14 to 21 days after treatment, determined with the use of the Kato-Katz thick-smear technique. Safety was assessed 3, 24, and 48 hours after the receipt of treatment or placebo. A total of 266 persons were enrolled in the <i>T. trichiura</i> trial and 176 in the hookworm trial. The predicted cure rate against <i>T. trichiura</i> in the 5-mg emodepside group (85% [95% confidence interval {CI}, 69 to 93]; 25 of 30 participants) was higher than the predicted cure rate in the placebo group (10% [95% CI, 3 to 26]; 3 of 31 participants) and the observed cure rate in the albendazole group (17% [95% CI, 6 to 35]; 5 of 30 participants). A dose-dependent relationship was shown in participants with hookworm: the observed cure rate was 32% (95% CI, 13 to 57; 6 of 19 participants) in the 5-mg emodepside group and 95% (95% CI, 74 to 99.9; 18 of 19 participants) in the 30-mg emodepside group; the observed cure rates were 14% (95% CI, 3 to 36; 3 of 21 participants) in the placebo group and 70% (95% CI, 46 to 88; 14 of 20 participants) in the albendazole group. In the emodepside groups, headache, blurred vision, and dizziness were the most commonly reported adverse events 3 and 24 hours after treatment; the incidence of events generally increased in a dose-dependent fashion. Most adverse events were mild in severity and were self-limited; there were few moderate and no serious adverse events. Emodepside showed activity against <i>T. trichiura</i> and hookworm infections. (Funded by the European Research Council; ClinicalTrials.gov number, NCT05017194.).