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   43865   clinical trials with a EudraCT protocol, of which   7286   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:
    A Phase IIa challenge study to assess efficacy of the Plasmodium vivax malaria vaccine candidates ChAd63 PvDBP and MVA PvDBP in healthy adults living in the UK

    Summary
    EudraCT number
    		 2019-000643-27
    Trial protocol
    		 GB  
    Global end of trial date
    07 Jul 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Oct 2022
    First version publication date
    11 Oct 2022
    Other versions
    Summary report(s)
    		 Impact of a blood-stage vaccine on Plasmodium vivax malaria

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    VAC071
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04009096
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University of Oxford
    Sponsor organisation address
    Old Road, Oxford, United Kingdom, OX3 7LE
    Public contact
    Angela Minassian, University of Oxford, +44 01865611338, angela.minassian@ndm.ox.ac.uk
    Scientific contact
    Angela Minassian, University of Oxford, +44 01865611338, angela.minassian@ndm.ox.ac.uk
    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
    Interim
    Date of interim/final analysis
    02 Sep 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Jul 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Jul 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess efficacy of the ChAd63 and MVA PvDBP vaccines, administered in a heterologous prime-boost regimen, as assessed by a reduced parasite multiplication rate in vaccinated subjects following a blood-stage parasite inoculum
    Protection of trial subjects
    Volunteers given at least 24 hours to read PIS before being seen and then given plenty of opportunity to ask questions prior to agreeing to take part in a study. Volunteers completed a questionnaire testing their understanding of the trial as part of the consent process to ensure that individuals understand the trial sufficiently to give informed consent. Screening visit including full medical history, physical examination and baseline blood tests to ensure volunteers are healthy prior to enrolment. Vaccination carried out in clinical environment with staff trained in resuscitation in case of allergic reaction. Volunteers observed for 1 hour after vaccination to monitor for any immediate adverse effects. Inclusion of AE related safety stopping/holding rules at both a group and individual level in the protocol. Volunteers given emergency contact card detailing that they have been infected with malaria. Volunteers seen once to twice daily during malaria challenge with measurement of parasitaemia at which visit Malaria treated promptly when diagnosed with highly efficacious medication and at least half of doses directly observed. Volunteers provided with symptomatic treatment (antipyretic/analgesic and antiemetic) in case of malaria symptoms. Volunteers who remained undiagnosed with malaria at Day 21 given a treatment course of anti-malarials. Volunteers followed up until at least 2 consecutive qPCR results with substantial reduction in genome copies/mL. Total blood volume taken during study kept to volume that should not compromise healthy volunteers.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 May 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 16
    Worldwide total number of subjects
    16
    EEA total number of subjects
    0
    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)
    16
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Volunteers were recruited by use of advertisements, formally approved by the ethics committee, distributed or posted in public places (including newspapers, social media, stalls at fairs and public transport) or via email distribution, including to individuals who have registered an interest in taking part in clinical trials at the study sites.

    Pre-assignment
    Screening details
    		 Screening visit consisted of Informed Consent, Informed Consent Questionnaire, Medical History, Physical Observations, Physical Examination, Urinalysis, Electrocardiogram, beta-HCG urine (women only), blood tests (HBV, HCV, HIV, EBV, CMV, Haematology, Biochemistry, DARC, G6PD). Review of screening visit results against inclusion/exclusion criteria

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group 1
    Arm description
    		 Volunteers receiving 5 x 10^10 vp ChAd63 PvDBP and 2 x 10^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ChAd63 PvDBP
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    5 x 10^10 vp ChAd63 PvDBP given at day 0

    Investigational medicinal product name
    MVA PvDBP
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 x 10^8 pfu MVA PvDBP given at 8 weeks after ChAd63 PvDBP

    Arm title
    		 Group 2
    Arm description
    		 Volunteers receiving one dose of 5 x 10^10 vp ChAd63 PvDBP, 12-18 months later receiving a second dose of 5 x 10^10 vp ChAd63 PvDBP and 8 weeks later 2 x 10^8 pfu MVA PvDBP, followed by blood-stage CHMI 2-4 weeks later.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ChAd63 PvDBP
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    5 x 10^10 vp ChAd63 PvDBP given at day 0, second dose of 5 x 10^10 vp ChAd63 PvDBP given at 12-18 months

    Investigational medicinal product name
    MVA PvDBP
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 x 10^8 pfu MVA PvDBP given 8 weeks after the second dose of ChAd63 PvDBP

    Arm title
    		 Group 3
    Arm description
    		 Volunteers receiving 5 x 10^10 vp ChAd63 PvDBP and 2 x10^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ChAd63 PvDBP
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    5 x 10^10 vp ChAd63 PvDBP given at day 0

    Investigational medicinal product name
    MVA PvDBP
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 x 10^8 pfu MVA PvDBP given at 8 weeks after ChAd63 PvDBP

    Number of subjects in period 1
    		Group 1 Group 2 Group 3
    Started
    3
    10
    3
    Primary CHMI
    3
    2
    3
    Completed
    3
    2
    3
    Not completed
    0
    8
    0
         Consent withdrawn by subject
    -
    7
    -
         Physician decision
    -
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Group 1
    Reporting group description
    		 Volunteers receiving 5 x 10^10 vp ChAd63 PvDBP and 2 x 10^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.

    Reporting group title
    Group 2
    Reporting group description
    		 Volunteers receiving one dose of 5 x 10^10 vp ChAd63 PvDBP, 12-18 months later receiving a second dose of 5 x 10^10 vp ChAd63 PvDBP and 8 weeks later 2 x 10^8 pfu MVA PvDBP, followed by blood-stage CHMI 2-4 weeks later.

    Reporting group title
    Group 3
    Reporting group description
    		 Volunteers receiving 5 x 10^10 vp ChAd63 PvDBP and 2 x10^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.

    Reporting group values
    		 Group 1 Group 2 Group 3 Total
    Number of subjects
    		 3 10 3 16
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 3 10 3 16
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 32 (29 to 38) 28 (20 to 44) 25 (21 to 29) -
    Gender categorical
    Units: Subjects
        Female
    		 2 4 1 7
        Male
    		 1 6 2 9

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Group 1
    Reporting group description
    		 Volunteers receiving 5 x 10^10 vp ChAd63 PvDBP and 2 x 10^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.

    Reporting group title
    Group 2
    Reporting group description
    		 Volunteers receiving one dose of 5 x 10^10 vp ChAd63 PvDBP, 12-18 months later receiving a second dose of 5 x 10^10 vp ChAd63 PvDBP and 8 weeks later 2 x 10^8 pfu MVA PvDBP, followed by blood-stage CHMI 2-4 weeks later.

    Reporting group title
    Group 3
    Reporting group description
    		 Volunteers receiving 5 x 10^10 vp ChAd63 PvDBP and 2 x10^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.

    Subject analysis set title
    Groups 1, 2 and 3
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pooled data of all Group 1, 2 and 3 volunteers

    Subject analysis set title
    Controls
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Infectivity controls from VAC069 study

    Primary: Efficacy of the ChAd63 and MVA PvDBP vaccines, administered in a heterologous prime-boost regimen, assessed by a reduced parasite multiplication rate in vaccinated subjects

    		 Close Top of page
    End point title
    		 Efficacy of the ChAd63 and MVA PvDBP vaccines, administered in a heterologous prime-boost regimen, assessed by a reduced parasite multiplication rate in vaccinated subjects
    End point description
    Quantitative PCR-derived parasite multiplication rate (PMR) will be the primary efficacy endpoint and a comparison of the endpoint between vaccinees and malaria-naïve controls partaking in simultaneous CHMI, under identical conditions, will constitute the primary analysis for efficacy.
    End point type
    Primary
    End point timeframe
    From day of controlled human malaria infection up to commencement of antimalarial treatment
    End point values
    		 Groups 1, 2 and 3 Controls
    Number of subjects analysed
    8 [1]
    13
    Units: parasite multiplication rate per 48hr
        median (full range (min-max))
    5.4 (4.0 to 7.3)
    6.8 (4.0 to 11.1)
    Notes
    [1] - Only volunteers who underwent CHMI are included in this analysis
    Statistical analysis title
    		 Comparison of PMR between vaccinees and controls
    Statistical analysis description
    Comparison of pooled data from Groups 1, 2 and 3 volunteers who completed CHMI with pooled data of infectivity controls (unvaccinated) from CHMI study running in parallel (VAC069 study)
    Comparison groups
    Controls v Groups 1, 2 and 3
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    P-value
    		 = 0.14 [3]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [2] - Test for significant difference between vaccinees and controls
    [3] - Two tailed p value reported for Mann-Whitney test comparing infectivity controls with vaccinees

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Serious adverse events were collected for the study duration.
    Adverse event reporting additional description
    Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Following ChAd63 PvDBP vaccination
    Reporting group description
    		 Volunteers who received at least one dose of ChAd63 PvDBP

    Reporting group title
    Following MVA PvDBP vaccination
    Reporting group description
    		 Volunteers who received vaccination with MVA PvDBP

    Serious adverse events
    		 Following ChAd63 PvDBP vaccination Following MVA PvDBP vaccination
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Following ChAd63 PvDBP vaccination Following MVA PvDBP vaccination
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 8 (0.00%)
    Reproductive system and breast disorders
    Dysmenorrhoea
    alternative assessment type: Non-systematic
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Apr 2019
    Addition of safety data from the VAC069 study. Addition of stopping and holding rules. Removal of barrier methods of contraception as an acceptable form of effective contraception, where used as the sole contraceptive. Addition of information relating to concomitant medications. Addition of exclusion criterion regarding receipt of licensed vaccines. Clarification of the definition of SARs and SUSARs
    14 Feb 2020
    Changes to exclusion criteria relating to haemoglobin levels at screening and prior exposure to immunoglobulins. Exclusion criteria relating to prior immunoglobulin exposure amended. Removal of thick blood film as diagnostic measure during CHMI for Group 2. Addition of repeat blood-borne viral screen at C+96. Updates and corrections to schedule of visits and bleed volumes, including reduction of maximal blood draw for Group 2. Addition of timing windows for recording physical observations on day of challenge. Clarifications to collection of adverse event data. Potential for use of alternative antiemetic to cyclizine. Removal of AEs of special interest. Change to group sizes (target range now specified). Clarification regarding timing of screening visits and for re-screening procedures for participants screened >90 days prior to enrolment. CRP added as an exploratory measure. Local safety monitor takes on role previously taken by local safety committee.
    26 Nov 2020
    Trial restart. Change of vaccination schedule for group 2 due to temporary trial halt. Justification for addition of second dose of ChAd63 PvDBP. Addition of Group 3, to be recruited if fewer than 6 participants complete the study in Group 2. C-1 visit changed to C-2. Extension of time window for study visits. Changes to trial procedures to account for possibility of COVID-19 infection during CHMI. Addition of COVID-19 PCR swab test prior to challenge and on day of malaria diagnosis. Guidance on testing for COVID-19 if fever post vaccination and post challenge. Added option of using Malarone as first line antimalaria treatment. Addition of serum bhCG to C+28/day of malaria diagnosis. Clarification that G6PD, DARC and haemoglobinopathy screen are only done at NHS labs. Correction of typographical errors. Addition of retrospective COVID-19 serology testing for exploratory analysis of effects of COVID serostatus on vaccine immunogenicity
    25 Jan 2021
    Clarification of exclusion criteria regarding concomitant vaccinations and addition of specific criteria relating to licensed COVID-19 vaccination. Extension of time window for MVA PvDBP vaccinations. Addition of section on administration of concomitant COVID-19 vaccination
    21 Apr 2021
    Addition of exclusion criteria on concomitant COVID-19 vaccination around time of CHMI. Shortened time window of when COVID-19 vaccination can be given following malaria vaccination to aid scheduling of COVID-19 vaccinations. Updated section on Conduct of CHMI in the context of COVID-19 pandemic. Addition of safety information on risk of blood clots with viral vectored COVID-19 vaccines in sections 4.5 and 8.5.2
    28 Jul 2021
    For Groups 2 and 3 - post-challenge follow-up visits changed to once a day until parasite count reaches >1000 genome copies/ml, then to continue twice a day visits until diagnosis. Latest day of treatment reduced to C+21. Addition of section 11.5.4 on initial follow-up visits post antimalarial treatment. For Groups 2 and 3 - change of post malaria treatment visit from T+2 to T+3. Correction of error in lumefantrine dose in section 8.5.5. Addition of reticulocyte count to FBC taken at C-2 visit. Correction of errors in protocol – only weight taken at C-2 visit. Changed Senior Laboratory Investigator address. Addition of New Biochemistry Building as location for processing of research bloods. Updated compensation table
    21 Jun 2022
    Samples will now be stored long term under University of Oxford’s HTA license at Department of Biochemistry instead of Oxford Vaccine Centre Biobank.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    27 Mar 2020
    Temporary trial halt during Covid-19 pandemic
    21 Jan 2021

    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-Mon Apr 29 07:56:09 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA