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

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: NCT03697668
Recruitment Status : Unknown
Verified October 2018 by Nurex S.r.l..
Recruitment status was:  Recruiting
First Posted : October 5, 2018
Last Update Posted : October 5, 2018
Sponsor:
Collaborators:
Università degli Studi di Sassari
Purdue University
Vinmec Healthcare System
Information provided by (Responsible Party):
Nurex S.r.l.

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.

Condition or disease Intervention/treatment Phase
Plasmodium Falciparum Malaria (Drug Resistant) Drug: Imatinib Drug: Dihydroartemisinin-piperaquine Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention 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).

Primary Purpose: Treatment
Official Title: Triple Antimalarial Combination (Imatinib-DHA-PPQ) to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites
Actual Study Start Date : September 17, 2017
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

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:
  • Artekin
  • Eurartesim
  • Diphos
  • Timequin
  • Duocotecxin




Primary Outcome Measures :
  1. Occurrence of Adverse Events [ Time Frame: From baseline to day 42 ]
    Occurrence of Adverse Events over 42 days observation period

  2. Occurrence of Severe Adverse Events [ Time Frame: From baseline to day 42 ]
    Occurrence of Severe Adverse Events over 42 days observation period

  3. Occurrence of Abnormal Physical Symptoms [ Time Frame: From baseline to day 42 ]
    Occurrence of Abnormal Physical Symptoms (Clinical Abnormalities) over 42 days observation period

  4. Occurrence of Abnormal Laboratory Values [ Time Frame: From baseline to day 42 ]
    Occurrence of Abnormal Laboratory Values over 42 days observation period


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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);

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03697668


Contacts
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Contact: Huynh D Chien, MD,PhD +84903580518 huynhdinhchien55@gmail.com
Contact: Tran A Tuan, MD +84982290426 tuanhuonghoa@gmail.com

Locations
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Vietnam
A Tuc Recruiting
Hương Hóa, Quang Tri, Vietnam, 520000
Contact: Tuan A Tran, MD    +84982290426    tuanhuonghoa@gmail.com   
Sponsors and Collaborators
Nurex S.r.l.
Università degli Studi di Sassari
Purdue University
Vinmec Healthcare System
Investigators
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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
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Responsible Party: Nurex S.r.l.
ClinicalTrials.gov Identifier: NCT03697668    
Other Study ID Numbers: NUREX S.r.l
First Posted: October 5, 2018    Key Record Dates
Last Update Posted: October 5, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Nurex S.r.l.:
Imatinib Mesylate
piperaquine phosphate
dihydroartemisinin
Additional relevant MeSH terms:
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Malaria, Falciparum
Malaria
Protozoan Infections
Parasitic Diseases
Infections
Vector Borne Diseases
Piperaquine
Artenimol
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents