Eurartesim® in Patients With Imported Uncomplicated Plasmodium Vivax Malaria

September 14, 2018 updated by: Alfasigma S.p.A.

Proof of Concept Study of Eurartesim® in Patients With Imported Uncomplicated Plasmodium Vivax Malaria

The aim of the present study is to investigate the efficacy, safety and tolerability of a therapeutic course of Eurartesim® in travellers who contracted malaria due to infection by P. vivax in endemic countries.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Vivax malaria occurs throughout the tropical, subtropical and some of the temperate latitudes globally. During a primary infection some P. vivax parasites become dormant in the liver (hypnozoites) during large periods of time and might subsequently cause multiple blood-stage relapses.

The asexual stages of P. vivax are generally still sensitive to chloroquine (CQ) throughout most of the world with the exception of Indonesia and Papua New Guinea where high therapeutic failure rates ranging from 5-84% have been reported. Also, there are reports of chloroquine failure from other countries and regions where the species is endemic; in particular, the presence of CQ-resistant vivax strains is now well described in several countries, including India, Brazil, Peru and Colombia.

The treatment of the dormant stages and the prevention of relapses is reached throughout the 8-aminoquinolines (primaquine is the only commercially available in this indication).

The current treatments recommended by World Health Organization (WHO) for the radical cure of CQ-resistant vivax malaria are Artemisinin based Combination Therapies (ACTs) with partner drugs having very long half-life, combined with a two weeks regiment of primaquine (WHO, 2010).

Among a variety of suitable artemisinin-based combinations, the fixed combination of dihydroartemisinin (DHA) and piperaquine (PQP )is considered an excellent therapeutic approach since it has got all the requirements considered essential for showing a positive benefit/risk ratio in malaria therapy.

Sigma-Tau i.f.r. S.p.A. has developed a DHA+PQP formulation (Eurartesim®) manufactured according to international Good Manufacturing Practice (GMP) standards and has recently received marketing authorization in Europe via a centralized procedure by the European Medicine Agency (EMA) for uncomplicated episodes of P. falciparum malaria.

A substantial amount of data have been collected in patients with uncomplicated P. falciparum malaria treated with the DHA+PQP combination. In addition, several studies have provided evidence of high cure rate in patients with P. vivax malaria treated with DHA+PQP, however, no data are available so far on efficacy and safety of the DHA+PQP treatment in patients with imported P. vivax malaria. Acquiring data is therefore of particular importance since malaria represents an important burden among all travel-acquired illnesses considering not only the number of cases (10-20% of the imported malaria cases are due to P. vivax infection) but also the potential of a fatal outcome.

The aim of the present study is to investigate the efficacy, safety and tolerability of a therapeutic course of Eurartesim® in travellers who contracted malaria due to infection by P. vivax in endemic countries. The results of such "proof of concept" study will be used for estimating the failure rate in a precise way and to dimension one or more subsequent phase III trials of comparative efficacy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
27

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bordeaux Cedex, France
        • Hôpital St André-CHU, Médecine interne et Maladies tropicales
  • Germany
      • Berlin, Germany
        • Medizinische Klinik mit Schwerpunkt Infektiologie, Charite/Campus Virchow-Klinikum
      • Munich, Germany
        • Department of Infectious Diseases & Tropical Medicine, University of Munich
  • Israel
      • Tel Hashomer, Israel
        • 15. The Center for Geographic Medicine and Tropical Diseases, Department of Medicine C - The Chaim Sheba Medical Center
  • Italy
      • Brescia, Italy
        • Clinica di Malattie Infettive e Tropicali, Universitá di Brescia
      • Milano, Italy, 20157
        • Azienda Ospedaliera Luigi Sacco
      • Reggio Emilia, Italy, 42123
        • Azienda Ospedaliera Arcispedale S. Maria Nuova IRCCS - Dip. Medicina Interna e Spec. Mediche
      • Roma, Italy
        • Centro di Malattie Tropicali - INMI Spallanzani
  • Netherlands
      • Leiden, Netherlands
        • Dep. Infectious Disease, Section Travel Medicine, Leiden University Medical Centre
  • Spain
      • Barcelona, Spain
        • CRESIB-Hospital Clinic, Barcelona
      • Barcelona, Spain
        • Hospital Vall D'Hebrón, Barcelona
  • Switzerland
      • Basel, Switzerland
        • Medical and Diagnostic Service Department, Swiss Tropical and Public Health Institute
      • Bern, Switzerland
        • Bern University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Have read the Information for the Patient and signed the Informed Consent Form;
  • Aged ≥18 years and able to swallow oral medication;
  • Body weight comprised between 24 kg and 100 kg (included) for males and females;
  • Uncomplicated malaria with microscopically confirmed monoinfection by Plasmodium vivax or mixed infection (i.e. infection with P. vivax and other Plasmodium species);
  • Willingness to comply with the study protocol and the study visit schedule.

Exclusion Criteria:

  • Participation in any investigational drug study during the previous 30 days;
  • Antimalarial treatment with chloroquine and quinine within the previous 6 weeks, with piperaquine-based compounds or mefloquine or lumefantrine within the previous 3 months and with halofantrine within the previous 30 days prior to screening;
  • P. vivax/Plasmodium species asexual stage parasitaemia ≥ 5% Red Blood Cells (in cases of mixed infection);
  • Clinical and/or laboratory features of severe malaria according to WHO criteria (WHO 2010);
  • ECG abnormality that requires urgent management (i.e. clinically significant arrhythmias, Atrio-Ventricular block II and III degree etc.);
  • Family history of sudden death, or known congenital prolongation of the QT interval
  • Lengthening of QT interval on ECG: corrected QT interval (Fridericia's correction) ≥450 ms for males and ≥470 ms for females;
  • Concomitant administration of any treatment which can induce a lengthening of QT interval (i.e. antihistamines, macrolides, etc.) and of any antimalarial drugs (for the full list of prohibited drugs refer to section 8.3);
  • Any contraindication to blood sampling (i.e. important haemorrhagic diathesis);;
  • Presence of intercurrent illness or any condition (i.e. severe vomiting and dehydration) which in the judgement of the Investigator would place the patient at undue risk or interfere with the study results;
  • Hypoglycaemia (blood glucose levels < 2.2 mmol/L or < 40 mg/dL);
  • Splenectomy;
  • Pregnant or lactating women. During the study period (Day 0- Day 42), fertile women who are sexually active must use an adequate birth control method. They should utilize oral or patch contraceptives, contraceptive implant or depot injection or an intrauterine device from at least one month before screening and during the whole study period. In all the other cases they have to agree to remain inactive or use condoms with a spermicidal agent during the study period;
  • Presence of jaundice;
  • Known renal impairment (serum creatinine > 2X the upper limit of the hospital laboratory reference range);
  • Known liver insufficiency (AST and/or ALT > 3X the upper limit of the hospital laboratory reference range);
  • Relevant anaemia (Hb< 8 g/dL).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Eurartesim tablets
Eurartesim 320 mg piperaquine / 40 mg dihydroartemisinin film coated tablets. one or more tablets according to the body weight, once a day dor three consecutive days.
Drug: Eurartesim tablets
dosage bands: 24 to <36 kg body weight: 2 tablets a day for three consecutive days 36 to <75 kg body weight: 3 tablets a day for three consecutive days 75 to 100 kg body weight: 4 tablets a day for three consecutive days
Other Names:
  • dihydroartemisinin/Piperaquine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Uncorrected adequate clinical and parasitological response (ACPR)
Time Frame: 21 days after the start of treatment
The uncorrected ACPR will be considered met for all those patients that are not presenting parasitaemia and fever at day 21 follow-up visit.
21 days after the start of treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of aparasitaemic patients
Time Frame: at day 1, 2, 3, 7, 21, 42
to evaluate efficacy of the treatment to clear blood from parasites
at day 1, 2, 3, 7, 21, 42
Proportion of afebrile patients
Time Frame: at day 1, 2, 3, 7, 21, 42
to evaluate the efficacy of eurartesim in reducing fever caused by malaria
at day 1, 2, 3, 7, 21, 42
uncorrected ACPR
Time Frame: at day 42
at day 42
Number of Patients with Serious and Non-Serious Adverse Events
Time Frame: up to 42 days from starting of treatment
up to 42 days from starting of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Alfasigma S.p.A.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Christoph Hatz, Prof Dr Med, Medical and Diagnostic Service Department, Swiss Tropical and Public Health Institute, Basel - Switzerland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 18, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 23, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 8, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 10, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 17, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ST3073-ST3074-DM13-001
  • 2013-003763-56 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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