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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02614404
Recruitment Status : Completed
First Posted : November 25, 2015
Last Update Posted : February 11, 2021
Sponsor:
Collaborators:
Purdue University
University of Turin, Italy
Università degli Studi di Sassari
Hue University
Information provided by (Responsible Party):
HuLow

Tracking Information
First Submitted Date  ICMJE November 16, 2015
First Posted Date  ICMJE November 25, 2015
Last Update Posted Date February 11, 2021
Actual Study Start Date  ICMJE November 2015
Actual Primary Completion Date December 2, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 23, 2015)
  • Time to Parasite Clearance [ Time Frame: 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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 23, 2015)
Frequency of adverse events [ Time Frame: 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.
  1. Incidence, severity, drug-relatedness, seriousness of adverse events
  2. Laboratory values (biochemistry and haematology)
  3. Vital signs
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Imatinib on Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria
Official Title  ICMJE Effect of Imatinib on Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Plasmodium Falciparum Malaria
Intervention  ICMJE
  • Drug: Imatinib combination therapy
    Imatinib plus dihydroartemisinin plus piperaquine
    Other Names:
    • Gleevec
    • Glivec
  • Drug: Dihydroartemisinin-piperaquine
    Standard of care
    Other Names:
    • Artekin
    • Eurartesim
    • Diphos
    • Timequin
    • Duocotecxin
    • Malacur
    • Ridmal
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Imatinib combination therapy
  • 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.
    Intervention: Drug: Dihydroartemisinin-piperaquine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 8, 2021)
15
Original Estimated Enrollment  ICMJE
 (submitted: November 23, 2015)
20
Actual Study Completion Date  ICMJE February 2, 2017
Actual Primary Completion Date December 2, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02614404
Other Study ID Numbers  ICMJE HuLow-201605
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party HuLow
Study Sponsor  ICMJE HuLow
Collaborators  ICMJE
  • Purdue University
  • University of Turin, Italy
  • Università degli Studi di Sassari
  • Hue University
Investigators  ICMJE
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
PRS Account HuLow
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP