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

Primary Purpose

Plasmodium Falciparum Malaria (Drug Resistant)

Status
Unknown status
Phase
Phase 2
Locations
Vietnam
Study Type
Interventional
Intervention
Imatinib
Dihydroartemisinin-piperaquine
Sponsored by
Nurex S.r.l.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Plasmodium Falciparum Malaria (Drug Resistant) focused on measuring Imatinib Mesylate, piperaquine phosphate, dihydroartemisinin

Eligibility Criteria

18 Years - 55 Years (Adult)MaleDoes not accept healthy volunteers

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);

Sites / Locations

  • A TucRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

imatinib-Dihydroartemisinin-piperaquine

Dihydroartemisinin-piperaquine

Arm Description

triple combination

standard of care

Outcomes

Primary Outcome Measures

Occurrence of Adverse Events
Occurrence of Adverse Events over 42 days observation period
Occurrence of Severe Adverse Events
Occurrence of Severe Adverse Events over 42 days observation period
Occurrence of Abnormal Physical Symptoms
Occurrence of Abnormal Physical Symptoms (Clinical Abnormalities) over 42 days observation period
Occurrence of Abnormal Laboratory Values
Occurrence of Abnormal Laboratory Values over 42 days observation period

Secondary Outcome Measures

Frequency of residual parasitemia: % of patients with >1000 parasites/ ul at day 3 and 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
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
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
Mean parasite clearance half-life calculated using parasitemia measured at baseline, 12 and 24 hours post-treatment

Full Information

First Posted
July 2, 2018
Last Updated
October 4, 2018
Sponsor
Nurex S.r.l.
Collaborators
Università degli Studi di Sassari, Purdue University, Vinmec Healthcare System
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1. Study Identification

Unique Protocol Identification Number
NCT03697668
Brief Title
Triple Antimalarial Combination to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites
Acronym
Artesynib
Official Title
Triple Antimalarial Combination (Imatinib-DHA-PPQ) to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Unknown status
Study Start Date
September 17, 2017 (Actual)
Primary Completion Date
December 31, 2018 (Anticipated)
Study Completion Date
December 31, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nurex S.r.l.
Collaborators
Università degli Studi di Sassari, Purdue University, Vinmec Healthcare System

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plasmodium Falciparum Malaria (Drug Resistant)
Keywords
Imatinib Mesylate, piperaquine phosphate, dihydroartemisinin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
interventional
Masking
None (Open Label)
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).
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
imatinib-Dihydroartemisinin-piperaquine
Arm Type
Experimental
Arm Description
triple combination
Arm Title
Dihydroartemisinin-piperaquine
Arm Type
Active Comparator
Arm Description
standard of care
Intervention Type
Drug
Intervention Name(s)
Imatinib
Other Intervention Name(s)
Gleevec, Glivec
Intervention Description
triple combination for the treatment of malaria
Intervention Type
Drug
Intervention Name(s)
Dihydroartemisinin-piperaquine
Other Intervention Name(s)
Artekin, Eurartesim, Diphos, Timequin, Duocotecxin
Intervention Description
standard malaria treatment
Primary Outcome Measure Information:
Title
Occurrence of Adverse Events
Description
Occurrence of Adverse Events over 42 days observation period
Time Frame
From baseline to day 42
Title
Occurrence of Severe Adverse Events
Description
Occurrence of Severe Adverse Events over 42 days observation period
Time Frame
From baseline to day 42
Title
Occurrence of Abnormal Physical Symptoms
Description
Occurrence of Abnormal Physical Symptoms (Clinical Abnormalities) over 42 days observation period
Time Frame
From baseline to day 42
Title
Occurrence of Abnormal Laboratory Values
Description
Occurrence of Abnormal Laboratory Values over 42 days observation period
Time Frame
From baseline to day 42
Secondary Outcome Measure Information:
Title
Frequency of residual parasitemia: % of patients with >1000 parasites/ ul at day 3 and 28
Description
Parasitemia is determined by assessing the parasite count in blood, using thin film, thick film and qPCR analysis.
Time Frame
day 3 and day 28
Title
Frequency of fever and malaria symptoms
Description
Percentage of patients with fever or malaria symptoms observed at Phisical Visit at day 3 and 28.
Time Frame
day 3 and day 28
Title
Mean parasitemia in the control and investigational arms
Description
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
Time Frame
day 2 and day 5
Title
Parasite half-life measured at 12 and 24 hours
Description
Mean parasite clearance half-life calculated using parasitemia measured at baseline, 12 and 24 hours post-treatment
Time Frame
from baseline to 24 hours post-treatment

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients diagnosed with mild to moderate P. falciparum malaria Adult male, age 18-55 years Good health conditions other than malaria The patient did not take anti-malarial drugs in the past 4 weeks Exclusion Criteria: unable to provide Informed Consent or Patient History Form symptoms and signs of severe or complicated malaria including: continuous high fever over 39 °C, confusion, convulsions parasitemia<150.000 parasites /microliter other neurological or psychiatric symptoms or disorders abnormal bleeding resting hearth rate lower than 60 and higher than 100 bpm abnormal ECG, history of cardiac diseases male adults with corrected QT intervals > 450ms signs, symptoms and laboratory results of impairment of vital organs such as liver, lungs, kidney and cardiovascular system hemoglobin < 9.0 gm/100ml symptoms and signs of infection such as pneumonia, dengue fever, and other viral or bacterial infection. patients with symptoms of gastrointestinal infections or any sign of malabsorption that may interfere with drug absorption concomitant infection by plasmodium species other than P. falciparum inability to meet daily with local doctor during period of clinical trial concomitant medicines like: medicines used to treat high cholesterol in the blood (such as atorvastatin, lovastatin, simvastatin); medicines used to treat hypertension and heart problems (such as diltiazem, nifedipine, nitrendipine, verapamil, felodipine, amlodipine); 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); medicines used to treat microbial infections (such as telithromycin, rifampicin, dapsone); medicines used to help you fall asleep: benzodiazepines (such as midazolam, triazolam, diazepam, alprazolam), zaleplon, zolpidem; medicines used to prevent/treat epileptic seizures: barbiturates (such as phenobarbital), carbamazepine or phenytoin; medicines used after organ transplantation and in autoimmune diseases (such as cyclosporin, tacrolimus); 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); paracetamol (used to treat pain and fever); theophylline (used to improve bronchial air flow); nefazodone (used to treat depression); aprepitant (used to treat nausea);
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Huynh D Chien, MD,PhD
Phone
+84903580518
Email
huynhdinhchien55@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Tran A Tuan, MD
Phone
+84982290426
Email
tuanhuonghoa@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Huynh D Chien, MD, PhD
Organizational Affiliation
UNIVERSITY OF HUE, VIETNAM AND VINMEC DANANG INTERNATIONAL HOSPITAL, Hai Chau, Danang.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Francesco M Turrini, MD, PhD
Organizational Affiliation
University of Turin, Italy
Official's Role
Principal Investigator
Facility Information:
Facility Name
A Tuc
City
Hương Hóa
State/Province
Quang Tri
ZIP/Postal Code
520000
Country
Vietnam
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tuan A Tran, MD
Phone
+84982290426
Email
tuanhuonghoa@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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