Safety and Efficacy of Imatinib in Combination With Artemether-Lumefantrine for Uncomplicated Malaria

NCT07559370 | Recruiting Phase 2 DMC

• 1 other identifier: VIBRI-ALIM01
• Study Type: interventional
• Target: 1,116
• Locations: 1 country
• Sites: 1

Brief Summary

This study is investigating an innovative approach to treating uncomplicated malaria by adding a drug called Imatinib to the current standard of care, Artemether + Lumefantrine (AL). The researchers hope this combination, known as ALIM, will clear infections faster and stop the spread of drug-resistant parasites that are becoming a major threat in Africa

Conditions

Malaria (Plasmodium Falciparum)

Keywords

Uncomplicated malaria; Artemether-lumefantrine (AL) combination therapy; Imatinib mesylate; Drug-resistant malaria; Parasite egress blockade

Outcome Measures

Primary Outcomes (3)

• Imatinib dose eliminating viable parasites after 2 days

  Identification of imatinib dose that eliminates all viable parasites after 2 days of dosing, determined by absence of viable parasites on blood culture from samples taken immediately after 48 hours of study drug administration.

  48 hours post-first dose

• Number and severity of adverse events

  Safety and tolerability of imatinib mesylate combined with artemether-lumefantrine (AL+IM) compared to artemether-lumefantrine alone (AL). Non-inferior safety defined as insignificant increase (p \> 0.05) in number and severity of adverse events in AL+IM cohorts versus AL alone.

  Up to Day 35

• Rate of recrudescence at Day 35

  Non-inferiority of 2-day AL+IM dosing compared to 3-day AL dosing as determined by PCR-corrected recrudescence using strain genotyping. Non-inferiority defined as insignificant increase (p \> 0.05) in recrudescence in 2-day AL+IM cohorts versus 3-day AL alone.

  Day 35

Secondary Outcomes (3)

• Parasite clearance rate

  Days 1, 2, and 3

• Fever clearance time

  Days 1, 2, and 3

• Parasite clearance in high baseline parasitemia

  Days 1, 2, and 3

Study Arms (5)

AL Alone

ACTIVE COMPARATOR

Standard 3-day course. Used as control in all parts.

Drug: Artemether/lumefantrine tablets

AL + Imatinib 400mg Twice Daily (3 days)

EXPERIMENTAL

3-day course with imatinib 400mg twice daily.

Drug: Artemether/Lumefantrine + Imatinib Mesylate

AL + Imatinib (Optimal Dose, 3 days)

EXPERIMENTAL

3-day course with optimal dose determined from Part 1.

Drug: Artemether/Lumefantrine + Imatinib Mesylate

AL + Imatinib (Optimal Dose, 2 days)

EXPERIMENTAL

2-day imatinib course (optimal dose) with 3-day AL.

Drug: Artemether/Lumefantrine + Imatinib Mesylate

Pediatric: AL + Imatinib (Weight-based)

EXPERIMENTAL

Weight-based imatinib (340 or 260 mg/m²/day, max 600mg) plus weight-based AL for 3 days.

Drug: Artemether/Lumefantrine + Imatinib Mesylate

Interventions

Artemether/lumefantrine tablets DRUG

There is no difference

AL Alone

Artemether/Lumefantrine + Imatinib Mesylate DRUG

There is no difference

AL + Imatinib (Optimal Dose, 2 days); AL + Imatinib (Optimal Dose, 3 days); AL + Imatinib 400mg Twice Daily (3 days); Pediatric: AL + Imatinib (Weight-based)

Eligibility Criteria

• Age: 1 Year - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients diagnosed with symptomatic mild to moderate P. falciparum malaria with a parasite density of \>= 5000 parasites/μl
• Adult male, age 18-55 years old or adult female, age 18-55 years that are post-menopausal, or test negative on a pregnancy test and will be on active birth control through to the end of the follow up period.
• Provision of informed consent and agrees to hospital admission for 48-72hrs
• Good health condition other than malaria
• The patient has not taken anti-malarial drugs in the past 4 weeks
• Patients diagnosed with symptomatic mild to moderate P. falciparum malaria and a parasite density of \>= 5000 parasites/μl
• Age 12 months to below 18 years
• Presented by parent or legally accepted representative (LAR) who has consented to the participation of the child in the trial and agrees to hospital admission for 48-72hrs.
• Hb levels \> 5mg/dL
• Child has not taken anti-malarial drugs in the past 6 weeks.

You may not qualify if:

• Prospective study participant, LAR and/or impartial witness (where applicable) declines to provide informed consent.
• Symptoms and signs of severe or complicated malaria including:
• significant confusion or impaired consciousness (including unarousable coma)
• multiple convulsions (more than two episodes within 24 hours),
• respiratory distress
• circulatory collapse (systolic blood pressure \<80mm Hg with evidence of impaired perfusion)
• clinical jaundice plus evidence of other vital organ dysfunction
• simultaneous infection of unrelated origin
• Parasite density \> 200,000 parasites /μl
• In the case of female participants: currently pregnant or lactating
• Other neurological or psychiatric symptoms or disorders
• Abnormal bleeding
• Resting heart rate lower than 55 or higher than 100 bpm
• History of cardiac disease
• Signs, symptoms and laboratory results of impairment of vital organs such as liver, lungs, kidney and cardiovascular system

Sponsors & Collaborators

• Victoria Biomedical Research Institute: lead

Study Sites (1)

Victoria Biomedical Research Institute

Kisumu, 40100, Kenya

RECRUITING

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artemether; Lumefantrine; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Dr. Quentin Awori MBChB

  Victoria Biomedical Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr. Quentin Awori, MBChB

CONTACT

+254722913616; qawori@vibriafrica.org

David Ogolla Awori, Msc

CONTACT

+254714421248; dogolla@vibriafrica.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Quentin Awori

Model Details: This study employs a three-part, adaptive, open-label, parallel assignment design with sequential dose de-escalation (Part 1), concurrent parallel group enrollment (Part 2), and sequential age de-escalation (Part 3). The model is not a traditional fixed parallel design because Parts 1 and 3 incorporate adaptive features based on real-time safety data.

Study Record Dates

• First Submitted: April 23, 2026
• First Posted: April 30, 2026
• Study Start: January 20, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

KE (1)