Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44293   clinical trials with a EudraCT protocol, of which   7351   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Controlled Human Malaria Infection study to assess gametocytaemia and mosquito transmissibility in participants challenged with Plasmodium falciparum by sporozoite challenge to establish a model for the evaluation of transmission-blocking interventions

    Summary
    EudraCT number
    		 2017-004005-40
    Trial protocol
    		 NL  
    Global end of trial date
    20 Nov 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Mar 2021
    First version publication date
    13 Mar 2021
    Other versions
    Summary report(s)
    		 Alkema M, Reuling IJ, de Jong GM, et al. A randomized clinical trial to compare P. falciparum gametocytaemia and infectivity following blood-stage or mosquito bite induced controlled malaria infection

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NL63552.000.17
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03454048
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Radboud university medical center
    Sponsor organisation address
    Geert Grooteplein Zuid 26-28, Nijmegen, Netherlands,
    Public contact
    teun.bousema@radboudumc.nl, Radboud university medical center, teun.bousema@radboudumc.nl
    Scientific contact
    teun.bousema@radboudumc.nl, Radboud university medical center, teun.bousema@radboudumc.nl
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    20 Nov 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 Nov 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Nov 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    1) To evaluate the safety of CHMI-trans protocols in healthy malaria-naïve volunteers challenged with Plasmodium falciparum by sporozoite challenge and blood stage challenge. 2) To assess gametocyte infectiousness for Anopheles mosquitoes through mosquito feeding assay (Direct Membrane Feeding Assay, DMFA).
    Protection of trial subjects
    Subjects were monitored twice daily on parasitaemia and adverse events, safety laboratory measurements were perfomed daily and a study physician is reachable 24 hours a day. An independend safety monitoring committee reviewed all safety data throughout set timepoint during the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Mar 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 24
    Worldwide total number of subjects
    24
    EEA total number of subjects
    24
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    24
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 From a total of 41 screened volunteers, 24 healthy adults were enrolled. Reasons for exclusion were: 4 invesigator's decision, 4 RhC and/or RhE incompatibility, 3 withdrew consent, 1 history of blood transfusion, 1 BMI>30, 1 CV risk profile (family history), 1 LFT abnormalities, 1 Recurrent UTIs.

    Period 1
    Period 1 title
    CHMI-trans2 (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group1 (Cohort A) LD-PIP/LD-PIP2/PIP
    Arm description
    		 Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Piperaquine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).

    Investigational medicinal product name
    malaria challenge infection by P. falciparum 3D7-infected mosquito bites
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intradermal use
    Dosage and administration details
    Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes.

    Arm title
    		 Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
    Arm description
    		 Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Piperaquine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).

    Investigational medicinal product name
    Sulfadoxine-pyrimethamine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).

    Investigational medicinal product name
    malaria challenge infection by P. falciparum 3D7-infected mosquito bites
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intradermal use
    Dosage and administration details
    Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes.

    Arm title
    		 Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
    Arm description
    		 Cohort B will be subjected to a standard blood stage challenge with ~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Piperaquine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).

    Investigational medicinal product name
    P. falciparum 3D7-infected human erythrocytes for the purpose controlled human malaria infection
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cohort B will be subjected to a standard blood stage challenge with ~2,800 Pf-infected erythrocytes by intravenous injection.

    Arm title
    		 Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Arm description
    		 Cohort B will be subjected to a standard blood stage challenge with ~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Piperaquine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).

    Investigational medicinal product name
    Sulfadoxine-pyrimethamine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).

    Investigational medicinal product name
    P. falciparum 3D7-infected human erythrocytes for the purpose controlled human malaria infection
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cohort B will be subjected to a standard blood stage challenge with ~2,800 Pf-infected erythrocytes by intravenous injection.

    Number of subjects in period 1
    		Group1 (Cohort A) LD-PIP/LD-PIP2/PIP Group 2 (Cohort A) LD-PIP/LD-PIP2/SP Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Started
    6
    6
    6
    6
    Completed
    6
    6
    6
    6

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Group1 (Cohort A) LD-PIP/LD-PIP2/PIP
    Reporting group description
    		 Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).

    Reporting group title
    Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
    Reporting group description
    		 Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).

    Reporting group title
    Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
    Reporting group description
    		 Cohort B will be subjected to a standard blood stage challenge with ~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)

    Reporting group title
    Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Reporting group description
    		 Cohort B will be subjected to a standard blood stage challenge with ~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).

    Reporting group values
    		 Group1 (Cohort A) LD-PIP/LD-PIP2/PIP Group 2 (Cohort A) LD-PIP/LD-PIP2/SP Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP Group 4 (Cohort B) LD-PIP/LD-PIP2/SP Total
    Number of subjects
    		 6 6 6 6 24
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 6 6 6 6 24
        From 65-84 years
    		 0 0 0 0 0
        85 years and over
    		 0 0 0 0 0
        Adults
    		 0 0 0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 24.5 (18 to 30) 22.5 (19 to 26) 25.5 (20 to 29) 20 (19 to 26) -
    Gender categorical
    Units: Subjects
        Female
    		 3 4 4 4 15
        Male
    		 3 2 2 2 9
    Hemoglobin
    Units: mmol/L
        median (full range (min-max))
    		 8.8 (8.0 to 9.7) 8.2 (7.6 to 909) 8.8 (7.6 to 10.0) 8.7 (7.5 to 9.4) -
    Body Mass Index
    Units: Kg/m2
        median (full range (min-max))
    		 22.2 (20.8 to 29.3) 24.2 (22.7 to 26.9) 20.4 (18.1 to 22.8) 24.7 (20.8 to 27.7) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Group1 (Cohort A) LD-PIP/LD-PIP2/PIP
    Reporting group description
    		 Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).

    Reporting group title
    Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
    Reporting group description
    		 Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).

    Reporting group title
    Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
    Reporting group description
    		 Cohort B will be subjected to a standard blood stage challenge with ~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)

    Reporting group title
    Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Reporting group description
    		 Cohort B will be subjected to a standard blood stage challenge with ~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).

    Primary: Frequency of adverse events

    		 Close Top of page
    End point title
    		 Frequency of adverse events [1]
    End point description
    End point type
    Primary
    End point timeframe
    Up to 51 days after challenge infection
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Frequency and magnitude of adverse events were primary safety endpoints to assess whether the CHMI-transmission model is in general safe and tolerable. For this purpose comparisons between study groups were not performed.
    End point values
    		 Group1 (Cohort A) LD-PIP/LD-PIP2/PIP Group 2 (Cohort A) LD-PIP/LD-PIP2/SP Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Number of subjects analysed
    6
    6
    6
    6
    Units: Number of adverse events
    95
    95
    107
    52
    No statistical analyses for this end point

    Primary: Magnitude of adverse events

    		 Close Top of page
    End point title
    		 Magnitude of adverse events [2]
    End point description
    symptoms will be ranked as (1) mild, (2) moderate, or (3) severe, depending on their intensity according to the following scale: Mild (grade 1): awareness of symptoms that are easily tolerated and do not interfere with usual daily activity Moderate (grade 2): discomfort that interferes with or limits usual daily activity Severe (grade 3): disabling, with subsequent inability to perform usual daily activity, resulting in absence or required bed rest
    End point type
    Primary
    End point timeframe
    Up to 51 days after challenge infection
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Frequency and magnitude of adverse events were primary safety endpoints to assess whether the CHMI-transmission model is in general safe and tolerable. For this purpose comparisons between study groups were not performed.
    End point values
    		 Group1 (Cohort A) LD-PIP/LD-PIP2/PIP Group 2 (Cohort A) LD-PIP/LD-PIP2/SP Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Number of subjects analysed
    6
    6
    6
    6
    Units: Number of adverse events
        Mild
    64
    56
    86
    41
        Moderate
    22
    22
    17
    8
        Severe
    9
    17
    4
    3
    No statistical analyses for this end point

    Primary: Infectious for Mosquitoes Through DMFA

    		 Close Top of page
    End point title
    		 Infectious for Mosquitoes Through DMFA
    End point description
    Prevalence of gametocyte infectiousness for Anopheles mosquitoes through Direct Membrane Feeding Assays (DMFA).
    End point type
    Primary
    End point timeframe
    up to day 51 after challenge infection
    End point values
    		 Group1 (Cohort A) LD-PIP/LD-PIP2/PIP Group 2 (Cohort A) LD-PIP/LD-PIP2/SP Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Number of subjects analysed
    6
    6
    6
    6
    Units: Number of subjects
    0
    0
    5
    2
    Statistical analysis title
    		 Infectiousness to mosquitoes
    Statistical analysis description
    The infectiousness to mosquitoes as determined by direct membrane feeding assay (DMFA) was compared between subjects of cohort A (groups 1 and 2) that were infected by mosquito bite and subjects of cohort B (groups 3 and 4) that were infected by induced blood stage malaria.
    Comparison groups
    Group1 (Cohort A) LD-PIP/LD-PIP2/PIP v Group 2 (Cohort A) LD-PIP/LD-PIP2/SP v Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP v Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.005
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Gametocyte prevalence

    		 Close Top of page
    End point title
    		 Gametocyte prevalence
    End point description
    Number of individuals in each study arm that show prevalence of gametocytes as defined by quantitative reverse-transcriptase PCR (qRT-PCR) for CCp4 (female) and PfMGET (male) mRNA with a threshold of 5 gametocytes/mL for positivity.
    End point type
    Secondary
    End point timeframe
    up to day 51 after challenge infection
    End point values
    		 Group1 (Cohort A) LD-PIP/LD-PIP2/PIP Group 2 (Cohort A) LD-PIP/LD-PIP2/SP Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Number of subjects analysed
    6
    6
    6
    6
    Units: Number of subjects
    5
    6
    6
    6
    No statistical analyses for this end point

    Secondary: Peak density gametocytes

    		 Close Top of page
    End point title
    		 Peak density gametocytes
    End point description
    Peak density of gametocytes by qRT-PCR.
    End point type
    Secondary
    End point timeframe
    up to day 51 after challenge infection
    End point values
    		 Group1 (Cohort A) LD-PIP/LD-PIP2/PIP Group 2 (Cohort A) LD-PIP/LD-PIP2/SP Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Number of subjects analysed
    6
    6
    6
    6
    Units: gametocytes/mL
        median (full range (min-max))
    13.9 (2.5 to 727.9)
    21.4 (6.16 to 181.6)
    1442.2 (246.6 to 3826.1)
    813.2 (179.5 to 1617.0)
    No statistical analyses for this end point

    Secondary: Infectiousness for Mosquitoes Through DFA

    		 Close Top of page
    End point title
    		 Infectiousness for Mosquitoes Through DFA
    End point description
    Prevalence of gametocyte infectiousness for Anopheles mosquitoes through Direct Feeding Assays (Direct Skin Feeding Assay, DFA).
    End point type
    Secondary
    End point timeframe
    Up to day 51 after challenge infection
    End point values
    		 Group1 (Cohort A) LD-PIP/LD-PIP2/PIP Group 2 (Cohort A) LD-PIP/LD-PIP2/SP Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Number of subjects analysed
    6
    6
    6
    6
    Units: Number of subjects
    0
    0
    5
    4
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    up to day 51 after challenge infection
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 ICD
    Dictionary version
    10
    Reporting groups
    Reporting group title
    Group1 (Cohort A) LD-PIP/LD-PIP2/PIP
    Reporting group description
    		 Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).

    Reporting group title
    Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
    Reporting group description
    		 Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).

    Reporting group title
    Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
    Reporting group description
    		 Cohort B will be subjected to a standard blood stage challenge with ~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)

    Reporting group title
    Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Reporting group description
    		 Cohort B will be subjected to a standard blood stage challenge with ~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).

    Serious adverse events
    		 Group1 (Cohort A) LD-PIP/LD-PIP2/PIP Group 2 (Cohort A) LD-PIP/LD-PIP2/SP Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Group1 (Cohort A) LD-PIP/LD-PIP2/PIP Group 2 (Cohort A) LD-PIP/LD-PIP2/SP Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Infections and infestations
    Fever
    Additional description: Tympanic or oral temperature >38.0 degrees Celcius
         subjects affected / exposed
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
         occurrences all number
    16
    11
    13
    5
    Chils
         subjects affected / exposed
    6 / 6 (100.00%)
    1 / 6 (16.67%)
    4 / 6 (66.67%)
    1 / 6 (16.67%)
         occurrences all number
    13
    2
    7
    2
    Abdominal pain
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    5 / 6 (83.33%)
    2 / 6 (33.33%)
         occurrences all number
    0
    2
    6
    2
    Fatigue
         subjects affected / exposed
    4 / 6 (66.67%)
    5 / 6 (83.33%)
    5 / 6 (83.33%)
    3 / 6 (50.00%)
         occurrences all number
    7
    13
    12
    6
    Headache
         subjects affected / exposed
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
         occurrences all number
    27
    26
    33
    20
    Malaise
         subjects affected / exposed
    4 / 6 (66.67%)
    4 / 6 (66.67%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
         occurrences all number
    8
    15
    3
    2
    Myalgia
         subjects affected / exposed
    1 / 6 (16.67%)
    5 / 6 (83.33%)
    4 / 6 (66.67%)
    4 / 6 (66.67%)
         occurrences all number
    1
    6
    7
    5
    Decreased appetite
         subjects affected / exposed
    3 / 6 (50.00%)
    2 / 6 (33.33%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    3
    2
    3
    0
    Nausea
         subjects affected / exposed
    5 / 6 (83.33%)
    4 / 6 (66.67%)
    6 / 6 (100.00%)
    3 / 6 (50.00%)
         occurrences all number
    13
    12
    9
    5
    Dizziness
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    2 / 6 (33.33%)
         occurrences all number
    5
    3
    8
    4
    Diarrhoea
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Palpitations
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Back pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Arthralgia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Thoracic pain
    Additional description: non specific
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA