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

Sponsor

Nurex S.r.l. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT03697668

Collaborator

Università degli Studi di Sassari (Other), Purdue University (Other), Vinmec Healthcare System (Other)

Enrollment

Location

Arms

27.4

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

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.

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

interventionalinterventional

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 :

Sep 17, 2017

Anticipated Primary Completion Date :

Dec 31, 2018

Anticipated Study Completion Date :

Dec 31, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Occurrence of Adverse Events [From baseline to day 42]
Occurrence of Adverse Events over 42 days observation period
Occurrence of Severe Adverse Events [From baseline to day 42]
Occurrence of Severe Adverse Events over 42 days observation period
Occurrence of Abnormal Physical Symptoms [From baseline to day 42]
Occurrence of Abnormal Physical Symptoms (Clinical Abnormalities) over 42 days observation period
Occurrence of Abnormal Laboratory Values [From baseline to day 42]
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 [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 [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 [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 [from baseline to 24 hours post-treatment]
Mean parasite clearance half-life calculated using parasitemia measured at baseline, 12 and 24 hours post-treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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);

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	A Tuc	Hương Hóa	Quang Tri	Vietnam	520000

Sponsors and Collaborators

Nurex S.r.l.
Università degli Studi di Sassari
Purdue University
Vinmec Healthcare System

Investigators

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