Clinical trial NCT02614404: Effect of Imatinib on Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria
Official title: Effect of Imatinib on Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Plasmodium Falciparum Malaria
Keywords: Plasmodium falciparum
Uncomplicated malarial
imatinib mesylate
antimalarials
Lead sponsor: HuLow
Sponsor class: INDUSTRY
Collaborators: name: Purdue University
name: University of Turin, Italy
name: Università degli Studi di Sassari
name: Hue University
First posted: 2015-11-25
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time to Parasite Clearance
timeFrame: From baseline to the time point when the blood parasite count is zero (up to a maximum of 5 days)
measure: 28-day Cure Rate
timeFrame: Day 28
Secondary outcomes:
measure: Frequency of adverse events
timeFrame: Within 1 week of beginning treatment with imatinib
Other outcomes:
Locations:
city: Huong Hoa
country: Vietnam
facility: A Tuc
state: Quang Tri
Study officials:
affiliation: Hue University
name: Huynh D Chien, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Turin, Italy
name: Francesco M Turrini, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Purdue University
name: Philip S Low, PhD
role: PRINCIPAL_INVESTIGATOR
References: