Clinical trial NCT03697668: Triple Antimalarial Combination to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites
Official title: Triple Antimalarial Combination (Imatinib-DHA-PPQ) to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Plasmodium Falciparum Malaria (Drug Resistant)
Keywords: Imatinib Mesylate
piperaquine phosphate
dihydroartemisinin
Lead sponsor: Nurex S.r.l.
Sponsor class: INDUSTRY
Collaborators: name: Università degli Studi di Sassari
name: Purdue University
name: Vinmec Healthcare System
First posted: 2018-10-05
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: interventional
Primary purpose: TREATMENT

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.

Eligibility 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);

Primary outcomes:
measure: Occurrence of Adverse Events
timeFrame: From baseline to day 42
measure: Occurrence of Severe Adverse Events
timeFrame: From baseline to day 42
measure: Occurrence of Abnormal Physical Symptoms
timeFrame: From baseline to day 42
measure: Occurrence of Abnormal Laboratory Values
timeFrame: From baseline to day 42
Secondary outcomes:
measure: Frequency of residual parasitemia: % of patients with >1000 parasites/ ul at day 3 and 28
timeFrame: day 3 and day 28
measure: Frequency of fever and malaria symptoms
timeFrame: day 3 and day 28
measure: Mean parasitemia in the control and investigational arms
timeFrame: day 2 and day 5
measure: Parasite half-life measured at 12 and 24 hours
timeFrame: from baseline to 24 hours post-treatment
Other outcomes:
Locations:
city: Hương Hóa
country: Vietnam
facility: A Tuc
state: Quang Tri
Study officials:
affiliation: UNIVERSITY OF HUE, VIETNAM AND VINMEC DANANG INTERNATIONAL HOSPITAL, Hai Chau, Danang.
name: Huynh D Chien, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Turin, Italy
name: Francesco M Turrini, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: