A Phase IIa, Proof-of-Concept, Placebo-Controlled, Randomised Trial to Investigate the Efficacy and Safety of Oxfendazole as a Macrofilaricidal Drug in Adults Harbouring Lymphatic Filarial Worms

INTRODUCTION: Lymphatic filariasis (LF) remains a significant public health concern, with India contributing nearly 55% of the global disease burden and placing approximately 487 million people at risk of infection. Despite the success of mass drug administration (MDA) programs in reducing microfilaraemia, the current regimens have limited macrofilaricidal activity, which hinders the achievement of LF elimination goals. The development of safe and effective drugs targeting adult filarial worms is, therefore, a critical priority. This phase IIa, proof-of-concept study aims to evaluate the efficacy, safety, and pharmacokinetic (PK) profile of oxfendazole in adults with confirmed LF. The primary objective is to estimate the proportion of participants with no detectable adult worm motility on ultrasonography (USG) at 6 months post-treatment, serving as a marker of macrofilaricidal efficacy. Secondary objectives include assessment of safety and tolerability, while exploratory objectives involve the characterization of the PK profile of oxfendazole in the study population. METHODS: The study is designed as a phase IIa, randomised, double-blind, placebo-controlled trial with three arms. Participants will be randomised to receive either 400 mg or 800 mg of oxfendazole, or a matching placebo, administered orally once daily for five consecutive days. Oxfendazole, a benzimidazole and structural analogue of flubendazole, has shown promising macrofilaricidal activity in preclinical models, demonstrating complete clearance of adult worms in mice. Phase I clinical studies have established its safety and tolerability in humans, supporting its progression to further clinical evaluation. Ethics approval has been obtained by the independent ethics committees (IEC) of all the participating study sites. This study will be performed in accordance with the Helsinki Declaration of 1964 and its later amendments, ICH-GCP, applicable regulatory requirements and approved study protocol. The details of ethics committee approvals are available in the supplementary material. PLANNED OUTCOMES: The findings from this trial will be pivotal in guiding the clinical development of oxfendazole, particularly in defining an optimal dosing regimen for use as a macrofilaricidal agent. If successful, this intervention could represent a significant advancement toward the elimination of LF. This study supports India's national target to eliminate LF by 2027 and aligns with the World Health Organization's global elimination goal by 2030.