Malaria, VivaxPhase 2NCT02110784
Eurartesim® in Patients With Imported Uncomplicated Plasmodium Vivax Malaria
A Phase 2 study testing Eurartesim tablets in people with Malaria, Vivax, run by Alfasigma S.p.A. at 13 sites in 7 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malaria, Vivax
- What is being tested?
- Eurartesim tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 13 sitesin 7 countries
- Study dates
- 18 Jun 2014to 30 Apr 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 17Show fewer
- 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).
Trial locations and contacts
13 sites in 7 countries.
13 sites in 7 countries
Italy4 sites
Clinica di Malattie Infettive e Tropicali, Universitá di Brescia
Brescia
Azienda ospedaliera Luigi Sacco
Milan, 20157
Azienda Ospedaliera Arcispedale S. Maria Nuova IRCCS - Dip. Medicina Interna e Spec. Mediche
Reggio Emilia, 42123
Centro di Malattie Tropicali - INMI Spallanzani
Roma
Germany2 sites
Medizinische Klinik mit Schwerpunkt Infektiologie, Charite/Campus Virchow-Klinikum
Berlin
Department of Infectious Diseases & Tropical Medicine, University of Munich
Munich
Spain2 sites
CRESIB-Hospital Clinic, Barcelona
Barcelona
Hospital Vall d'Hebron, Barcelona
Barcelona
Switzerland2 sites
Medical and Diagnostic Service Department, Swiss Tropical and Public Health Institute
Basel
Bern University Hospital
Bern
France1 site
Hôpital St André-CHU, Médecine interne et Maladies tropicales
Bordeaux
Israel1 site
15. The Center for Geographic Medicine and Tropical Diseases, Department of Medicine C - The Chaim Sheba Medical Center
Tel HaShomer
Netherlands1 site
Dep. Infectious Disease, Section Travel Medicine, Leiden University Medical Centre
Leiden
About this study
Official title: 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.
Read the 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.
- Conditions
- Malaria, Vivax
- Being tested
- Eurartesim tablets
- Keywords
- Artemisinin based Combination Therapies, eurartesim, Dihydroartemisinin/Piperaquine
- Medical subject headings
- Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eurartesim tabletsDrug
Also called dihydroartemisinin/Piperaquine
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
| Study group | Role | What they receive |
|---|---|---|
| Eurartesim tablets | Experimental | 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. Receives: Drug: Eurartesim tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Uncorrected adequate clinical and parasitological response (ACPR)
The uncorrected ACPR will be considered met for all those patients that are not presenting parasitaemia and fever at day 21 follow-up visit.
Measured: 21 days after the start of treatment
Secondary outcomes (4)
Proportion of aparasitaemic patients
to evaluate efficacy of the treatment to clear blood from parasites
Measured: at day 1, 2, 3, 7, 21, 42
Proportion of afebrile patients
to evaluate the efficacy of eurartesim in reducing fever caused by malaria
Measured: at day 1, 2, 3, 7, 21, 42
uncorrected ACPR
Measured: at day 42
Number of Patients with Serious and Non-Serious Adverse Events
Measured: up to 42 days from starting of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2014 (estimated)
- Study start18 Jun 2014
- Primary completion23 Nov 2016
- Study completion30 Apr 2017
Why it stopped: Low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Malaria, VivaxStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alfasigma S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christoph Hatz, Prof Dr Med, Study chair, Medical and Diagnostic Service Department, Swiss Tropical and Public Health Institute, Basel - Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02110784
- Sponsor's protocol ID
- ST3073-ST3074-DM13-001
- Other IDs
- 2013-003763-56
- Status last verified
- Jun 2017
- First submitted
- 8 Apr 2014
- Last updated
- 17 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Hasugian AR, Purba HL, Kenangalem E, Wuwung RM, Ebsworth EP, Maristela R, Penttinen PM, Laihad F, Anstey NM, Tjitra E, Price RN. Dihydroartemisinin-piperaquine versus artesunate-amodiaquine: superior efficacy and posttreatment prophylaxis against multidrug-resistant Plasmodium falciparum and Plasmodium vivax malaria. Clin Infect Dis. 2007 Apr 15;44(8):1067-74. doi: 10.1086/512677. Epub 2007 Mar 5.
PubMed 17366451Ratcliff A, Siswantoro H, Kenangalem E, Maristela R, Wuwung RM, Laihad F, Ebsworth EP, Anstey NM, Tjitra E, Price RN. Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison. Lancet. 2007 Mar 3;369(9563):757-765. doi: 10.1016/S0140-6736(07)60160-3.
PubMed 17336652Sinclair D, Gogtay N, Brand F, Olliaro P. Artemisinin-based combination therapy for treating uncomplicated Plasmodium vivax malaria. Cochrane Database Syst Rev. 2011 Jul 6;(7):CD008492. doi: 10.1002/14651858.CD008492.pub2.
PubMed 21735431
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proof of Concept Study of Eurartesim® in Patients With Imported Uncomplicated Plasmodium Vivax Malaria
- ClinicalTrials.gov ID
- NCT02110784
- Acronym / sponsor ID
- ST3073-ST3074-DM13-001
- Conditions
- Malaria, Vivax
- Keywords
- Artemisinin based Combination Therapies, eurartesim, Dihydroartemisinin/Piperaquine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Alfasigma S.p.A.Industry (pharma, biotech, devices)
- Study start
- 18 Jun 2014 (actual)
- Primary completion
- 23 Nov 2016 (actual)
- Study completion
- 30 Apr 2017 (actual)
- First posted
- 10 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eurartesim tablets | Experimental | Drug: Eurartesim tabletsEurartesim 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eurartesim tabletsAlso: dihydroartemisinin/Piperaquinedosage 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 | Drug | Eurartesim tablets |
Primary outcome
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.
4 secondary outcomes
Proportion of aparasitaemic patients
Time frame: at day 1, 2, 3, 7, 21, 42
Proportion of afebrile patients
Time frame: at day 1, 2, 3, 7, 21, 42
uncorrected ACPR
Time frame: at day 42
Number of Patients with Serious and Non-Serious Adverse Events
Time frame: up to 42 days from starting of treatment
Results and safety
The study was stopped early (reason given: Low recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2018.
- Background: PubMed 17366451Hasugian AR, Purba HL, Kenangalem E, Wuwung RM, Ebsworth EP, Maristela R, Penttinen PM, Laihad F, Anstey NM, Tjitra E, Price RN. Dihydroartemisinin-piperaquine versus artesunate-amodiaquine: superior efficacy and posttreatment prophylaxis against multidrug-resistant Plasmodium falciparum and Plasmodium vivax malaria. Clin Infect Dis. 2007 Apr 15;44(8):1067-74. doi: 10.1086/512677. Epub 2007 Mar 5.
- Background: PubMed 17336652Ratcliff A, Siswantoro H, Kenangalem E, Maristela R, Wuwung RM, Laihad F, Ebsworth EP, Anstey NM, Tjitra E, Price RN. Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison. Lancet. 2007 Mar 3;369(9563):757-765. doi: 10.1016/S0140-6736(07)60160-3.
- Background: PubMed 21735431Sinclair D, Gogtay N, Brand F, Olliaro P. Artemisinin-based combination therapy for treating uncomplicated Plasmodium vivax malaria. Cochrane Database Syst Rev. 2011 Jul 6;(7):CD008492. doi: 10.1002/14651858.CD008492.pub2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christoph Hatz, Prof Dr Med study chair
Medical and Diagnostic Service Department, Swiss Tropical and Public Health Institute, Basel - Switzerland
13 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eurartesim tablets in people with Malaria, Vivax, run by Alfasigma S.p.A. at 13 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Italy, Germany, Spain, Switzerland, France and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Uncorrected adequate clinical and parasitological response (ACPR) (time frame: 21 days after the start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02110784, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2018.