Clinical trial NCT06252961: A 3- to 5-day Clinical Trial of Levamisole in Loiasis Infected Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Loiasis
Keywords: Onchocerciasis
Filariasis
Levamisole
Lead sponsor: Programme National de Lutte contre l'Onchocercose, Republic of the Congo
Sponsor class: OTHER_GOV
Collaborators: name: Institut de Recherche pour le Developpement
First posted: 2024-02-12
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A 3-group, randomized, double-blind, parallel clinical trial:

* Levamisole 2.5 mg for 3 days (followed by 2 days placebo),
* Levamisole 2.5 mg for 5 days,
* Placebo for 5 days.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Tolerance of multiple doses of levamisole 2.5 mg/kg in individuals with Loa loa microfilaremia
timeFrame: During the treatment (5 days) and 2 weeks after
Secondary outcomes:
measure: Efficacy of multiple doses of levamisole 2.5 mg/kg on Loa loa microfilaremia
timeFrame: From Day 3 after the first dose to Day 30 after the first dose
Other outcomes:
Locations:
city: Sibiti
country: Congo
facility: Supervisor
state: Komono
city: Sibiti
country: Congo
facility: General Supervisor
state: Mokassi
Study officials:
affiliation: Institut de Recherche pour le Développement (IRD)
name: Jéremy CAMPILLO, PharmD PhD
role: STUDY_DIRECTOR
affiliation: Programme National de Lutte contre l'Onchocercose (PNLO)
name: François MISSAMOU, MD
role: PRINCIPAL_INVESTIGATOR
References: