Plasmodium Falciparum MalariaPhase 1MIMNCT02614404
Effect of Imatinib on Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria
A Phase 1 study testing Imatinib combination therapy and Dihydroartemisinin-piperaquine in people with Plasmodium Falciparum Malaria, run by HuLow at 1 site in Vietnam.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Plasmodium Falciparum Malaria
- What is being tested?
- Imatinib combination therapy and Dihydroartemisinin-piperaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteVietnam
- Study dates
- Nov 2015to 2 Feb 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Imatinib combination therapy, Dihydroartemisinin-piperaquine
- Keywords
- Plasmodium falciparum, Uncomplicated malarial, imatinib mesylate, antimalarials
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib combination therapyDrug
Also called Gleevec, Glivec
Imatinib plus dihydroartemisinin plus piperaquine
Dihydroartemisinin-piperaquineDrug
Also called Artekin, Eurartesim, Diphos, Timequin
Standard of care
| Study group | Role | What they receive |
|---|---|---|
| Imatinib combination therapy | Experimental | 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. Receives: Drug: Imatinib combination therapy |
| dihydroartemisinin plus piperaquine | Active comparator | 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. Receives: Drug: Dihydroartemisinin-piperaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Parasite Clearance
Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and qPCR analysis
Measured: From baseline to the time point when the blood parasite count is zero (up to a maximum of 5 days)
28-day Cure Rate
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.
Measured: Day 28
Secondary outcomes (1)
Frequency of adverse events
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
Measured: Within 1 week of beginning treatment with imatinib
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2015 (estimated)
- Study startNov 2015
- Primary completion2 Dec 2016
- Study completion2 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Plasmodium Falciparum MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- HuLow
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Purdue University, University of Turin, Italy, Università degli Studi di Sassari, Hue University
- Responsible party
- Sponsor
- Investigators
- Huynh D Chien, MD, PhD, Principal investigator, Hue UniversityFrancesco M Turrini, MD, PhD, Principal investigator, University of Turin, ItalyPhilip S Low, PhD, Principal investigator, Purdue University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02614404
- Sponsor's protocol ID
- HuLow-201605
- Acronym
- MIM
- Status last verified
- Feb 2021
- First submitted
- 16 Nov 2015
- Last updated
- 11 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Imatinib on Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria
- ClinicalTrials.gov ID
- NCT02614404
- Acronym / sponsor ID
- MIM / HuLow-201605
- Conditions
- Plasmodium Falciparum Malaria
- Keywords
- Plasmodium falciparum, Uncomplicated malarial, imatinib mesylate, antimalarials
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- HuLowIndustry (pharma, biotech, devices)
- Collaborators
- Purdue University, University of Turin, Italy, Università degli Studi di Sassari, Hue University
- Study start
- Nov 2015 (actual)
- Primary completion
- 2 Dec 2016 (actual)
- Study completion
- 2 Feb 2017 (actual)
- First posted
- 25 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Imatinib combination therapy | Experimental | Drug: Imatinib combination therapyAdministration 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. |
| dihydroartemisinin plus piperaquine | Active comparator | Drug: Dihydroartemisinin-piperaquineAdministration 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imatinib combination therapyAlso: Gleevec, GlivecImatinib plus dihydroartemisinin plus piperaquine | Drug | Imatinib combination therapy |
| Dihydroartemisinin-piperaquineAlso: Artekin, Eurartesim, Diphos, TimequinStandard of care | Drug | dihydroartemisinin plus piperaquine |
Primary outcome
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.
1 secondary outcome
Frequency of adverse events
Time frame: Within 1 week of beginning treatment with imatinib
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Huynh D Chien, MD, PhD principal investigator
Hue University
Francesco M Turrini, MD, PhD principal investigator
University of Turin, Italy
Philip S Low, PhD principal investigator
Purdue University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Imatinib combination therapy and Dihydroartemisinin-piperaquine in people with Plasmodium Falciparum Malaria, run by HuLow at 1 site in Vietnam.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2021.