A 3- to 5-day Clinical Trial of Levamisole in Loiasis Infected Subjects (STOP-FiLAR)

Randomized, Double-blind Trial Evaluating the Safety and Efficacy of a 3- or 5- Day Course of Levamisole 2.5 mg/kg in Subjects With Loa Loa Microfilaremia

The aim of the study is to evaluate the safety and efficacy of a 3- and 5-day course of levamisole (2.5 mg/kg) in management of loiasis microfilaremia.

Study Overview

• Status: Not yet recruiting
• Conditions: Loiasis
• Intervention / Treatment: Drug: Placebo; Drug: Levamisole 3 days; Drug: Levamisole 5 days

Detailed Description

Onchocerciasis and loiasis are parasitic diseases caused by Onchocerca volvulus and Loa loa, respectively.

Onchocerciasis is endemic in 31 African countries, parts of South America, and Yemen, affecting around 37 million people, while loiasis is present in Central Africa, infecting approximately 15 million individuals. Both diseases are associated with severe complications and increased mortality.

African countries have implemented mass drug administration (MDA) programs using ivermectin to combat onchocerciasis. However, co-endemic loiasis poses challenges due to the risk of severe adverse events. Current strategies involve alternative treatments and chemoprophylaxis to accelerate onchocerciasis elimination. The project aims to evaluate the use of levamisole as an alternative treatment.

This project will assess the safety and efficacy of administering levamisole for 3 and 5 days to reduce Loa microfilarial density. Previous research demonstrated the safety of a single dose of levamisole but indicated the need for longer treatment regimens to achieve a significant reduction in Loa microfilarial density. The project aims to test whether 3- and 5-day levamisole regimens induce an acceptable safety profile and a stronger reduction in Loa microfilarial density.

• Study Type: Interventional
• Enrollment (Estimated): 99
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jéremy CAMPILLO, PharmD PhD; Phone Number: +33 4 67 41 61 52; Email: jeremy.campillo@ird.fr
• Study Contact Backup: Name: Bachiratou SAHM; Email: bachiratou.sahm@ird.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Consent informed, written, signed and dated
• Women or men aged 18 to 65 years inclusive
• Carrier of L. loa microfilaremia
• Body weight ≥ 40 kg in women and ≥ 45 kg in men; and less than 90 kg
• In good health, as determined by medical questionnaire and general clinical examination
• Absence of acute or chronic infection :

Exclusion criteria

• Participation in any study other than a purely observational study, within the 4 weeks preceding this study (determined by the theoretical date of the first administration of levamisole or placebo)
• Any vaccination within 4 weeks previous to this study
• Infection requiring treatment in the 10 days previous to this study, as determined by the anamnesis during the medical interview (e.g. pulmonary infection , digestive or skin infection; with or without antibiotic treatment)
• Treatment with clozapine, phenothiazines, sulfasalazine, carbamazepine, synthetic antithyroid drugs, ticlopidine, cimetidine, and gold salts: whether it was long-term treatment, or treatment given as a single dose 10 days before the start of treatment for the clinical trial (precaution with regard to the risk of agranulocytosis of immuno-allergic or toxic origin)
• Known immunosuppressive pathology (by self-report)
• Past or present history of neurological (including epilepsy) or neuropsychiatric disease
• History of agranulocytosis
• Use of cocaine or other drugs of abuse in the 72 hours preceding administration of the trial treatment, as determined by history during the medical interview
• Any condition, in the opinion of the investigator, that exposes the subject to undue risk
• Known intolerance to levamisole
• Subjects who donated blood in the previous 8 weeks to study entry, with a standard volume (> 500 mL)
• On clinical examination: symptoms, physical signs or laboratory findings suggestive of systemic disorders, including disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other abnormalities that could interfere with the interpretation of trial results. The physician may then give a favorable or unfavorable opinion on the participant's inclusion.
• Ivermectin and/or levamisole taken in the last six months; and/or mebendazole or albendazole taken in the last month
• Pregnant and/or breast-feeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levamisole 3 days; Participants randomized in this arm will receive 3 days of levamisole 2.5mg/kg, followed by 2 days of placebo	Drug: Levamisole 3 days; Levamisole for 3 days (2,5 mg/kg) then placebo for 2 days
Experimental: Levamisole 5 days; Participants randomized in this arm will receive a 5-day course of levamisole 2.5mg/kg	Drug: Levamisole 5 days; Levamisole for 5 days (2,5 mg/kg)
Placebo Comparator: Placebo; Participants randomized in this arm will receive 5 days of placebo	Drug: Placebo; Placebo for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance of multiple doses of levamisole 2.5 mg/kg in individuals with Loa loa microfilaremia	The proportions of adverse reactions and severe adverse reactions between the three arms of study will be compared, as well as between each interventional arm versus placebo, using appropriate comparative tests A multivariate analysis may be envisaged to assess the influence of age, gender and the presence or absence of M. perstans on the proportion of AEs	During the treatment (5 days) and 2 weeks after

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of multiple doses of levamisole 2.5 mg/kg on Loa loa microfilaremia	Microfilaremia reduction rates will be compared between arms at Day 3, Day 5, Day 7, Day 15 and Day 30. The proportions of subjects who had reduced their microfiflaremia by at least 80% at D3, D5, D7, D15 and D30 will be compared Finally, a multivariate analysis could be carried out to assess the influence of age, gender and the presence or absence of M. perstans on the reduction of the microfilaremia.	From Day 3 after the first dose to Day 30 after the first dose

Collaborators and Investigators

• Sponsor: Programme National de Lutte contre l'Onchocercose, Republic of the Congo
• Collaborators: Institut de Recherche pour le Developpement
• Investigators: Study Director: Jéremy CAMPILLO, PharmD PhD, Institut de Recherche pour le Développement (IRD); Principal Investigator: François MISSAMOU, MD, Programme National de Lutte contre l'Onchocercose (PNLO)

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: January 22, 2024
• First Submitted That Met QC Criteria: February 1, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Onchocerciasis; Levamisole; Filariasis
• Additional Relevant MeSH Terms: Infections; Parasitic Diseases; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Filariasis; Loiasis; Physiological Effects of Drugs; Anti-Infective Agents; Antirheumatic Agents; Immunologic Factors; Adjuvants, Immunologic; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Levamisole
• Other Study ID Numbers: Protocole128

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No