Effect of Imatinib on Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria

NCT ID: NCT02614404

Last Updated: 2021-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2017-02-02

Brief Summary

The purpose of this study is to determine the efficacy and safety of imatinib in combination with dihydroartemisinin plus piperaquine in the treatment uncomplicated P. falciparum malaria in adult male patients.

Detailed Description

An exploratory study to examine the efficacy and safety of imatinib mesylate in combination with dihydroartemisinin plus piperaquine on suppression of parasitemia in patients with uncomplicated Plasmodium falciparum malaria. In vitro studies of P. falciparum parasitized erythrocytes demonstrate that inhibitors of the protein tyrosine kinase SYK prevent malaria parasite egress from infected red blood cells and thereby terminate the parasite's life cycle. Although no potent syk kinase inhibitors were approved for human use at the time of initiation of this study, a bcr-abl tyrosine kinase inhibitor (imatinib mesylate (Gleevec®)) that also exhibits off-target inhibition of syk tyrosine kinase, has been FDA-approved for treatment of a number of human malignancies including chronic myelogenous leukemia and GIST. Because imatinib can be taken daily for many years without significant toxicity, it can be used to obtain a preliminary indication of whether inhibition of erythrocyte syk kinase can suppress parasitemia in patients with P. falciparum malaria. In a phase 1 clinical trial on the same patient population, anti-malaria activity was observed with imatinib, with little or no accompanying toxicity. Because dihydroartemisinin plus piperaquine constitute the currently used standard-of-care therapy for malaria in Southeast Asia, the above trial will test the safety and efficacy of the combination of imatinib plus dihydroartemisinin and piperaquine in treatment of uncomplicated malaria. In this pilot study, the rate of decrease in peripheral blood parasitemia in 30 adult male patients with uncomplicated malaria will be compared to the same rate of decrease in parasitemia in 30 adult male patients treated solely with dihydroartemisinin plus piperaquine.

Conditions

Plasmodium Falciparum Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imatinib combination therapy

Administration of imatinib (400 mg/day) plus dihydroartemisinin (40 mg/day) plus piperaquine (320 mg/day) to uncomplicated adult male malaria patients. Normal health parameters will be monitored continuously to evaluate safety and the decrease in peripheral blood parasitemia with time will be quantitated to assess efficacy.

Group Type: EXPERIMENTAL

Imatinib combination therapy

Intervention Type: DRUG

Imatinib plus dihydroartemisinin plus piperaquine

dihydroartemisinin plus piperaquine

Administration of dihydroartemisinin (40 mg/day) plus piperaquine (320 mg/day) to uncomplicated adult male malaria patients. Normal health parameters will be monitored continuously to evaluate safety and the decrease in peripheral blood parasitemia with time will be quantitated to assess efficacy.

Group Type: ACTIVE_COMPARATOR

Dihydroartemisinin-piperaquine

Intervention Type: DRUG

Standard of care

Interventions

Imatinib combination therapy

Imatinib plus dihydroartemisinin plus piperaquine

Intervention Type: DRUG

Dihydroartemisinin-piperaquine

Standard of care

Intervention Type: DRUG

Other Intervention Names

Gleevec; Glivec; Artekin; Eurartesim; Diphos; Timequin; Duocotecxin; Malacur; Ridmal

Eligibility Criteria

Inclusion Criteria

• Gender: only adults are selected for the trial; note that female subjects cannot be women of child-bearing age.
• Age: 18-50 years.
• Target disease: Uncomplicated Plasmodium falciparum malaria

Exclusion Criteria

• symptoms and signs of complicated malaria
• including continuous high fever of over 390C, psychiatric disorders, confusion, other neurological symptoms, symptoms and signs of functional impairment of the organs such as lungs, kidneys or cardiovascular system;
• symptoms and signs of liver damage or kidney damage
• symptoms and signs of another complicating infection such as pneumonia, dengue fever, and other bacterial infection.
• P. falciparum > 25.000 / mm3
• WBC <4000 and >10.000 /mm3

• RBC < 3.5x106/mm3
• Platelets < 40.000 /mm3
• Hemoglobin < 10 g/dL
• ALT more than 200% of the upper limit (56 units/L)
• AST more than 200% of the upper limit (40 units/L)
• Blood creatine more than 75% of the upper limit (men: 1.2 mg/dL, women 1 mgdL)
• Serum total protein < 6 g/L
• Glycemia < 50 mg/dL> 200 mg/dL
• Standard urine test Serious alterations
• Concomitant treatments

Antimalarial Drugs Anticoagulant therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Purdue University

OTHER

Sponsor Role: collaborator

University of Turin, Italy

OTHER

Sponsor Role: collaborator

Università degli Studi di Sassari

OTHER

Sponsor Role: collaborator

Hue University

OTHER

Sponsor Role: collaborator

HuLow

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Huynh D Chien, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hue University

Francesco M Turrini, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Turin, Italy

Philip S Low, PhD

Role: PRINCIPAL_INVESTIGATOR

Purdue University

Locations

A Tuc

Hương Hóa, Quang Tri, Vietnam

Countries

Vietnam

Other Identifiers

HuLow-201605

Identifier Type: -

Identifier Source: org_study_id