Moxidectin for LF Cote d'Ivoire (DOLF)

Description

This study will test the hypothesis that Moxidectin combination therapies are superior to ivermectin combination therapies for achieving sustained clearance of W. bancrofti microfilaremia.

This trial is designed as single-site, Phase III, randomized, open-label, masked-observer superiority trial with four treatment arms: ivermectin + albendazole (IA), moxidectin + albendazole (MoxA), ivermectin + diethylcarbamazine + albendazole (IDA), and moxidectin + diethylcarbamabzine + albendazole (MoxDA). The primary endpoint is the proportion of participants achieving complete clearance of microfilaremia at 12 months (IA vs. MoxA comparison) or 24 months (IDA vs. MoxDA comparison). Block randomization by gender will be used to assign treatment arms.

The first 48 participants (12 each arm) will be treated at Agboville Hospital in Cote d'Ivoire at the Centre de Recherche de Filariose with inpatient AE monitoring and collection of post-treatment plasma drug levels (Part 1). For Part 1, active AE surveillance will be conducted in the hospital on days 1, 2, and 3, post-treatment, and in the participant's village of residence on day 7 post-treatment and passive surveillance will be conducted by trained village health workers on days 4-6. An interim safety analysis will take place after Part 1. If no safety concerns are identified, the remainder of the participants will be treated in their home villages, with active AE monitoring on days 1 and 2 post-treatment (Part 2) with passive surveillance by trained village health workers on days 3-7. Any participant in either Part 1 or Part 2 experiencing AEs of grade 2 or higher will be followed until adverse event (AE) severity falls below grade 2. Follow-up assessments for efficacy of treatments for all participants (Parts 1 and 2) will be conducted at 6, 12, 24, and 36 months.

The study includes both safety and efficacy analyses. The safety assessment (Part 1 only) ends 7 days after treatment (unless AEs remain grade 2 or higher). The efficacy assessment (Parts 1 and 2 combined) ends when participants are retested for filarial infection 36 months post-treatment. Participants in the IA arm will receive IA annually (standard of care). Participants in the other arms will receive the assigned treatment at baseline; those found to be microfilaremic at 24 months post-treatment will be retreated with the same treatment received at baseline. If clearance of microfilariae (Mf) at 12 months in the IA arm is superior to Mf clearance in the MoxA arm, the MoxA group will be switched to annual IA treatment.

The study design does not currently include stratification, nor do any sub-studies. However, the study may stratify based on pre-treatment Mf levels if high variability among pre-screening Mf counts is observed.

Details