Triple Antimalarial Combination to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites

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Tracking Information

First Submitted Date ^ICMJE

July 2, 2018

First Posted Date ^ICMJE

October 5, 2018

Last Update Posted Date

October 5, 2018

Actual Study Start Date ^ICMJE

September 17, 2017

Estimated Primary Completion Date

December 31, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Occurrence of Adverse Events[ Time Frame: From baseline to day 42 ]

Occurrence of Adverse Events over 42 days observation period

Occurrence of Severe Adverse Events[ Time Frame: From baseline to day 42 ]

Occurrence of Severe Adverse Events over 42 days observation period

Occurrence of Abnormal Physical Symptoms[ Time Frame: From baseline to day 42 ]

Occurrence of Abnormal Physical Symptoms (Clinical Abnormalities) over 42 days observation period

Occurrence of Abnormal Laboratory Values[ Time Frame: From baseline to day 42 ]

Occurrence of Abnormal Laboratory Values over 42 days observation period

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Frequency of residual parasitemia: % of patients with >1000 parasites/ ul at day 3 and 28[ Time Frame: day 3 and day 28 ]
Parasitemia is determined by assessing the parasite count in blood, using thin film, thick film and qPCR analysis.
Frequency of fever and malaria symptoms[ Time Frame: day 3 and day 28 ]
Percentage of patients with fever or malaria symptoms observed at Phisical Visit at day 3 and 28.
Mean parasitemia in the control and investigational arms[ Time Frame: day 2 and day 5 ]
Mean parasitemia by assessing the parasite count in blood, using thin film, thick film and qPCR analysis, expressed as parasites / ul at day 2, 3 and 5 measured in the control and investigational arms
Parasite half-life measured at 12 and 24 hours[ Time Frame: from baseline to 24 hours post-treatment ]
Mean parasite clearance half-life calculated using parasitemia measured at baseline, 12 and 24 hours post-treatment

Descriptive Information

Brief Title ^ICMJE

Triple Antimalarial Combination to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites

Official Title ^ICMJE

Triple Antimalarial Combination (Imatinib-DHA-PPQ) to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites

Brief Summary

The purpose of this study is to provide a new drug combination for a better treatment of P. falciparum for a faster parasite clearance and to counteract artemisinin resistance.

Detailed Description

According to WHO, resistance to artemisinin derivatives (ART) is emerging in many areas of the Greater Mekong Region as a delayed parasite clearance following a standard treatment by artemisinin combined therapy (ACT). Artemisinin resistance is often accompanied by the resistance to the partner drugs such as piperaquine (PPQ), mefloquine (MEF), amodiaquine (AQ) and lumefantrine (LF). The slow and incomplete clearance of parasites following ACT treatment is considered to permit the selection of resistant parasites. The availability of new, more efficient treatments accelerating the clearance of parasites is therefore needed to counteract the selection of ART resistant strains. Imatinib (IMA) has been demonstrated to increase the efficacy of ART in a synergic fashion. This positive effect is further potentiated by low concentrations of PPQ. IMA is active both on the intra-erythrocyte asexual forms and on gametocytes. It is therefore expected that the combination DHA-PPQ-IMA should lead to faster and radical clearance of the parasites, therefore reducing the frequency of healthy carriers and transmission.

Study Type ^ICMJE

Interventional

Study Phase

Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: interventional
Masking: Interventional
Masking Description:The research method will be a Phase 2 trial, 2 arms, randomized, open label (only the microscopist will be blinded), adaptive, dose de-escalation, trial conducted in adult male subjects with uncomplicated P.falciparum malaria. In all phases, patients will be treated by a triple combination IMA-DHA-PPQ (ARM 1) or by the standard DHA-PPQ treatment (ARM 2).
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Drug: Imatinib
triple combination for the treatment of malaria
Drug: Dihydroartemisinin-piperaquine
standard malaria treatment

Study Arms

Experimental: imatinib-Dihydroartemisinin-piperaquine
triple combination
Active Comparator: Dihydroartemisinin-piperaquine
standard of care

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

December 31, 2019

Estimated Primary Completion Date

December 31, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria: 1. Patients diagnosed with mild to moderate P. falciparum malaria 2. Adult male, age 18-55 years 3. Good health conditions other than malaria 4. The patient did not take anti-malarial drugs in the past 4 weeks Exclusion Criteria: 1. unable to provide Informed Consent or Patient History Form 2. symptoms and signs of severe or complicated malaria including: continuous high fever over 39 °C, confusion, convulsions 3. parasitemia<150.000 parasites /microliter 4. other neurological or psychiatric symptoms or disorders 5. abnormal bleeding 6. resting hearth rate lower than 60 and higher than 100 bpm 7. abnormal ECG, history of cardiac diseases 8. male adults with corrected QT intervals > 450ms 9. signs, symptoms and laboratory results of impairment of vital organs such as liver, lungs, kidney and cardiovascular system 10. hemoglobin < 9.0 gm/100ml 11. symptoms and signs of infection such as pneumonia, dengue fever, and other viral or bacterial infection. 12. patients with symptoms of gastrointestinal infections or any sign of malabsorption that may interfere with drug absorption 13. concomitant infection by plasmodium species other than P. falciparum 14. inability to meet daily with local doctor during period of clinical trial 15. concomitant medicines like: 1. medicines used to treat high cholesterol in the blood (such as atorvastatin, lovastatin, simvastatin); 2. medicines used to treat hypertension and heart problems (such as diltiazem, nifedipine, nitrendipine, verapamil, felodipine, amlodipine); 3. medicined used to treat HIV (antiretroviral medicines): protease inhibitors (such as amprenavir, atazanavir, indinavir, nelfinavir, ritonavir), non-nucleoside reverse transcriptase inhibitors (such as efavirenz, nevirapine); 4. medicines used to treat microbial infections (such as telithromycin, rifampicin, dapsone); 5. medicines used to help you fall asleep: benzodiazepines (such as midazolam, triazolam, diazepam, alprazolam), zaleplon, zolpidem; 6. medicines used to prevent/treat epileptic seizures: barbiturates (such as phenobarbital), carbamazepine or phenytoin; 7. medicines used after organ transplantation and in autoimmune diseases (such as cyclosporin, tacrolimus); 8. sex hormones, including those contained in hormonal contraceptives (such as gestodene, progesterone, estradiol), testosterone; - glucocorticoids (hydrocortisone, dexamethasone); - omeprazole (used to treat diseases related to gastric acid production); 9. paracetamol (used to treat pain and fever); 10. theophylline (used to improve bronchial air flow); 11. nefazodone (used to treat depression); 12. aprepitant (used to treat nausea);

Sex/Gender

Sexes Eligible for Study:

Male

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

Vietnam

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

Nurex S.r.l.

Collaborators ^ICMJE

Investigators ^ICMJE

Principal Investigator: Huynh D Chien, MD, PhD UNIVERSITY OF HUE, VIETNAM AND VINMEC DANANG INTERNATIONAL HOSPITAL, Hai Chau, Danang.
Principal Investigator: Francesco M Turrini, MD, PhD University of Turin, Italy

PRS Account

Verification Date

October 2018

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

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