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

Sponsor

HuLow (Industry)

Overall Status

Completed

CT.gov ID

NCT02614404

Collaborator

Purdue University (Other), University of Turin, Italy (Other), Università degli Studi di Sassari (Other), Hue University (Other)

Enrollment

Location

Arms

15.1

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Plasmodium Falciparum Malaria	Drug: Imatinib combination therapy Drug: Dihydroartemisinin-piperaquine	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 1, 2015

Actual Primary Completion Date :

Dec 2, 2016

Actual Study Completion Date :

Feb 2, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Imatinib combination therapy Imatinib plus dihydroartemisinin plus piperaquine Other Names: Gleevec Glivec
Active Comparator: 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.	Drug: Dihydroartemisinin-piperaquine Standard of care Other Names: Artekin Eurartesim Diphos Timequin Duocotecxin Malacur Ridmal

Arm

Intervention/Treatment

Experimental: 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.

Drug: Imatinib combination therapy

Imatinib plus dihydroartemisinin plus piperaquine

Other Names:

Gleevec

Glivec

Active Comparator: 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.

Drug: Dihydroartemisinin-piperaquine

Standard of care

Other Names:

Artekin

Eurartesim

Diphos

Timequin

Duocotecxin

Malacur

Ridmal

Outcome Measures

Primary Outcome Measures

Time to Parasite Clearance [From baseline to the time point when the blood parasite count is zero (up to a maximum of 5 days)]
Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and qPCR analysis
28-day Cure Rate [Day 28]
28-day cure rate was defined as the percentage of participants with blood parasite count of zero after 28 days of treatment and no evidence of recurrent infection with the same parasite genotype after reduction of the asexual parasitemia. Follow up after treatment will only be performed in the case of complete clearance of parasites at D5 due to Imatinib treatment.

Secondary Outcome Measures

Frequency of adverse events [Within 1 week of beginning treatment with imatinib]
Adverse events (AEs) are defined as events possibly related to the study drug as judged by physician that occur within 1 week of beginning treatment with imatinib. Incidence, severity, drug-relatedness, seriousness of adverse events Laboratory values (biochemistry and haematology) Vital signs

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	A Tuc	Huong Hoa	Quang Tri	Vietnam	520000

Sponsors and Collaborators

HuLow
Purdue University
University of Turin, Italy
Università degli Studi di Sassari
Hue University

Investigators

Principal Investigator: Huynh D Chien, MD, PhD, Hue University
Principal Investigator: Francesco M Turrini, MD, PhD, University of Turin, Italy
Principal Investigator: Philip S Low, PhD, Purdue University