Clinical trial NCT04410406: Moxidectin for LF, Cote d'Ivoire (DOLF)
Official title: A Clinical Trial to Assess the Safety and Efficacy of Moxidectin Combination Treatments vs. Ivermectin Combination Treatments for Bancroftian Filariasis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Lymphatic Filariasis
Keywords: moxidectin
ivermectin
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Case Western Reserve University
name: Regional Hospital of Agboville, Southern Cote d'Ivoire
First posted: 2020-06-01
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial is a single-site, Phase III, randomized, open-label, masked-observer superiority trial with four treatment arms (IA, MoxA, IDA, and MoxDA). Block randomization by gender will be used to assign treatment arms.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether moxidectin (Mox) will be more effective than ivermectin (IVM) when used in single-dose combination therapies for lymphatic filariasis (LF).

Detailed 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 + diethylcarbamazine + 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.

Eligibility criteria: Inclusion Criteria:

* Provision of signed and dated informed consent form
* Male or female, aged 18-70 years
* In good general health as evidenced by medical history
* Peripheral night blood W. bancrofti Mf levels ≥40 Mf/mL
* No history of taking antifilarial medications in past 12 months
* Resident of the study area with no plans to change residence in the next 36 months
* For women of childbearing potential, willing to use appropriate method of contraception for one month following each treatment

Exclusion Criteria:

* Pregnancy or currently breastfeeding
* Known allergic reactions to any of the study medications
* Evidence of severe or systemic comorbidities (aside from features of filarial disease), as judged by the principal investigator
* Baseline biochemical abnormalities, as indicated by AST, ALT, or creatinine \> 2 times the upper limit of normal
* Evidence of urinary tract infection as indicated by 3+ nitrites on dipstick (individuals with 1+ or 2+ nitrites will not be excluded) or underlying chronic kidney disease as indicated by 3+ protein or 3+ blood on urine dipstick exam
* Hgb \< 7 gm/dL (any such individuals will be referred to the local health center for evaluation and treatment)
* Positive skin snip for onchocerciasis

Primary outcomes:
measure: Clearance of microfilaremia (IA vs. MoxA)
timeFrame: 12 months
measure: Clearance of microfilaremia (IDA vs. MoxDA)
timeFrame: 24 months
Secondary outcomes:
measure: Clearance of microfilaremia
timeFrame: 6, 12, 24, & 36 months
measure: Reduction in Mf counts
timeFrame: Baseline, 6, 12, & 24 months
measure: Reduction in circulating filarial antigen (CFA) counts
timeFrame: Baseline, 6, 12, & 24 months
measure: Inactivation of adult worm nests
timeFrame: 6, 12, & 24 months
measure: Frequency and severity of AEs
timeFrame: From baseline treatment to 7 days post-treatment
measure: Plasma levels of drugs/metabolites post treatment
timeFrame: Baseline, 2, 3, 4, 6, 12, 24, & 48 hours post-treatment
Other outcomes:
Locations:
city: Agboville
country: Côte D'Ivoire
facility: Regional Hospital of Agboville, Southern Cote d'Ivoire
Study officials:
affiliation: Washington University School of Medicine
name: Philip Budge, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University
name: Catherine Bjerum, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Regional Hospital of Agboville, Southern Cote d'Ivoire
name: Toki Pascal Gabo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Regional Hospital of Agboville, Southern Cote d'Ivoire
name: Benjamin Koudou, PhD
role: PRINCIPAL_INVESTIGATOR
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