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

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

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.

Study Overview

• Status: Unknown
• Conditions: Plasmodium Falciparum Malaria (Drug Resistant)
• Intervention / Treatment: Drug: Imatinib; Drug: Dihydroartemisinin-piperaquine

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: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Vietnam
  • Quang Tri
    • Hương Hóa, Quang Tri, Vietnam, 520000
      • Recruiting
      • A Tuc
      • Contact: Tuan A Tran, MD; Phone Number: +84982290426; Email: tuanhuonghoa@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: imatinib-Dihydroartemisinin-piperaquine; triple combination	Drug: Imatinib; triple combination for the treatment of malaria; Other Names: Gleevec; Glivec
ACTIVE_COMPARATOR: Dihydroartemisinin-piperaquine; standard of care	Drug: Dihydroartemisinin-piperaquine; standard malaria treatment; Other Names: Eurartesim; Artekin; Diphos; Timequin; Duocotecxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Adverse Events	Occurrence of Adverse Events over 42 days observation period	From baseline to day 42
Occurrence of Severe Adverse Events	Occurrence of Severe Adverse Events over 42 days observation period	From baseline to day 42
Occurrence of Abnormal Physical Symptoms	Occurrence of Abnormal Physical Symptoms (Clinical Abnormalities) over 42 days observation period	From baseline to day 42
Occurrence of Abnormal Laboratory Values	Occurrence of Abnormal Laboratory Values over 42 days observation period	From baseline to day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	day 3 and day 28
Frequency of fever and malaria symptoms	Percentage of patients with fever or malaria symptoms observed at Phisical Visit at day 3 and 28.	day 3 and day 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	day 2 and day 5
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	from baseline to 24 hours post-treatment

Collaborators and Investigators

• Sponsor: Nurex S.r.l.
• Collaborators: Purdue University; Università degli Studi di Sassari; Vinmec Healthcare System
• Investigators: Principal Investigator: Huynh D Chien, MD, PhD, UNIVERSITY OF HUE, VIETNAM AND VINMEC DANANG INTERNATIONAL HOSPITAL, Hai Chau, Danang.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 17, 2017
• Primary Completion (ANTICIPATED): December 31, 2018
• Study Completion (ANTICIPATED): December 31, 2019

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: October 4, 2018
• First Posted (ACTUAL): October 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 5, 2018
• Last Update Submitted That Met QC Criteria: October 4, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Imatinib Mesylate; dihydroartemisinin; piperaquine phosphate
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Imatinib Mesylate; Piperaquine; Artenimol
• Other Study ID Numbers: NUREX S.r.l

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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