Efficacy and safety of oxfendazole in adults with spp. infection in Pemba Island, Tanzania: a double-blind, phase 2a, randomised controlled trial.

BACKGROUND: Trichuriasis caused by the intestinal parasites and remains a major public health problem. The widely used benzimidazoles albendazole and mebendazole show low efficacy, highlighting that more effective treatments are needed. One promising candidate is oxfendazole, a highly effective anthelminthic that is widely used in veterinary medicine. Within eWHORM, an adaptive basket trial platform for neglected helminth infections was set up to evaluate the safety and efficacy of oxfendazole against, among others, trichuriasis.

METHODS: In this double-blind, phase 2a, randomised, placebo-controlled trial conducted between April 29 and July 16, 2025, on Pemba Island, Tanzania, we evaluated the safety and efficacy of oxfendazole against spp. infection in adults aged 18-65 years. A total of 127 participants were randomised in a 1:1:1:1 ratio to receive either placebo on three consecutive days, 400 mg oxfendazole on day 1 followed by placebo on two consecutive days, 800 mg oxfendazole on day 1 followed by placebo on two consecutive days or 800 mg oxfendazole on three consecutive days. The primary outcome was spp. egg count at day 18, expressed as eggs per gram of stool based on quadruplicate Kato-Katz thick smears. Secondary outcomes included cure rates and egg reduction rates for spp., , and hookworm. Adverse events were recorded 3 h, 24 h, and 18 days post-treatment. The trial is registered at the Pan African Clinical Trials Registry (PACTR202412611774752).

FINDINGS: Between April 29 and May 21, 2025, 229 participants were screened for spp. infection, of whom 127 were treated. Of these, 31 received 3 × 800 mg oxfendazole, 34 received 1 × 800 mg oxfendazole, 30 received 1 × 400 mg oxfendazole and 32 received placebo. The egg count at day 18 was 1099.2 (SD 3354.6) for placebo, 218.3 (SD 506.4) for 1 × 400 mg oxfendazole, 148.4 (SD 244.7) for 1 × 800 mg oxfendazole and 36.2 (SD 117.5) for 3 × 800 mg oxfendazole. Cure rate for 3 × 800 mg oxfendazole was 75.9% (95% CI 57.9-87.8). Single oxfendazole doses revealed lower cure rates of 31.0% (95% CI 17.3-49.2) at 400 mg and 35.3% (95% CI 21.5-52.1) at 800 mg. The placebo group had a cure rate of 20.0% (95% CI 9.5-37.3). All doses were well tolerated and showed a similar number of adverse events compared to placebo. The most common adverse event was abdominal pain.

INTERPRETATION: Single doses of oxfendazole showed no benefit over the cure rates reported in the literature for the currently used drugs albendazole and mebendazole against spp. infections. However, given its high efficacy when used at multiple doses, the drug could play a role in targeted treatment schemes. Moreover, multiple-dose administration of oxfendazole may confer an ancillary public health benefit against spp. when used to treat helminth infections requiring multi-day regimens, particularly in co-endemic regions.

FUNDING: EDCTP3 Joint Undertaking and the Swiss State Secretariat for Education, Research and Innovation (SERI).

© 2026 The Author(s).

PMID: 42990826