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VAC071: A Study to Assess Efficacy of the ChAd63/MVA PvDBP Vaccines

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ClinicalTrials.gov Identifier: NCT04009096
Recruitment Status : Not yet recruiting
First Posted : July 4, 2019
Last Update Posted : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
University of Oxford

Brief Summary:

This is an open label, Phase IIa, controlled human malaria infection (CHMI) study aimed to assess whether the new vivax malaria vaccines ChAd63 PvDBP and MVA PvDBP can protect against malaria infection.

The participants will receive two vaccinations, one dose of each vaccine, administered 8 weeks apart.

Approximately 4 weeks after the second vacccination, the volunteers will be challenged (deliberately infected) with malaria by intravenous injection blood-stage


Condition or disease Intervention/treatment Phase
Malaria, Vivax Biological: ChAd63 PvDBP and MVA PvDBP Phase 2

Detailed Description:

Volunteers will be recruited and vaccinated at the CCVTM, Oxford.

There will be two vaccinated groups across two phases of the trial, with a total of 15 volunteers. These will be compared to 15 infectivity controls who will be recruited as part of a separate study (VAC069 - NCT03797989).

Study participants will be involved in this trial for approximately 1 year.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: 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
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Group 1
3 volunteers receiving one dose of 5 x 10^10 vp ChAd63 PvDBP and one dose of 2 x 10^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2 weeks later.
Biological: ChAd63 PvDBP and MVA PvDBP
one dose of 5 x 10^10 vp ChAd63 PvDBP and one dose of 2 x 10^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen.

Experimental: Group 2
12 volunteers receiving one dose of 5 x 10^10 vp ChAd63 PvDBP and one dose of 2 x 10^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2 weeks later.
Biological: ChAd63 PvDBP and MVA PvDBP
one dose of 5 x 10^10 vp ChAd63 PvDBP and one dose of 2 x 10^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen.




Primary Outcome Measures :
  1. 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 [ Time Frame: 3 months ]
    Quantitative PCR-derived parasite multiplication rate (PMR) will be the primary efficacy endpoint and a comparison of the endpoint between Groups 1 and 2 (pooled data) and malaria-naïve controls partaking in simultaneous CHMI, under identical conditions, will constitute the primary analysis for efficacy.


Secondary Outcome Measures :
  1. Safety of the ChAd63 and MVA PvDBP vaccines andidates, administered in a heterologous prime-boost regimen in a CHMI study in healthy volunteers [ Time Frame: for approximately 1 year following priming with ChAd63 PvDBP ]
    The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events.

  2. The humoral immunogenicity ChAd63 and MVA PvDBP vaccine candidates, administered in a heterologous prime-boost regimen [ Time Frame: 3 months ]
    Antibody responses to the P. vivax Duffy-binding protein (PvDBP) - total IgG, isotypes and avidity

  3. The cellular immunogenicity ChAd63 and MVA PvDBP vaccine candidates, administered in a heterologous prime-boost regimen [ Time Frame: 3 months ]
    T cell responses to PvDBP by ex-vivo ELISpot and flow cytometry assays and in vitro functional PvDBP_RII inhibitory binding assays.

  4. Immunological readouts for association with a reduced parasite multiplication rate [ Time Frame: 3 months ]
    Statistical correlation between anti-PvDBP antibody responses induced by the ChAd63 and MVA PvDBP vaccines and PMR.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adult aged 18 to 45 years.
  • Red blood cells positive for the Duffy antigen/chemokine receptor (DARC).
  • Normal serum levels of Glucose-6-phosphate dehydrogenase (G6PD).
  • Able and willing (in the Investigator's opinion) to comply with all study requirements.
  • Willing to allow the Investigators to discuss the volunteer's medical history with their General Practitioner.
  • Women only: Must practice continuous effective contraception* for the duration of the study
  • Agreement to permanently refrain from blood donation
  • Written informed consent to participate in the trial.
  • Reachable (24/7) by mobile phone during the period between CHMI and completion of all antimalarial treatment.
  • Willing to take a curative anti-malarial regimen following CHMI.
  • Willing to reside in Oxford for the duration of the study, until antimalarials have been completed.
  • Answer all questions on the informed consent quiz correctly.

    • Female volunteers are required to use an effective form of contraception during the course of the study as malaria challenge could pose a serious risk to both maternal health and the unborn foetus.

Exclusion Criteria:

  • History of clinical malaria (any species).
  • Travel to a clearly malaria endemic locality during the study period or within the preceding six months.
  • Current or planned treatment with long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
  • Chronic use of antibiotics with antimalarial effects (e.g. tetracyclines for dermatologic patients, trimethoprim-sulfamethoxazole for recurrent urinary tract infections, etc.).
  • Haemoglobin <125 g/L for a female volunteer or <135 g/L for a male volunteer), as measured at screening
  • Weight less than 50kg, as measured at the screening visit
  • Use of immunoglobulins or blood products (e.g., blood transfusion) at any time in the past
  • Peripheral venous access unlikely to allow twice daily blood testing (as determined by the Investigator)
  • Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period
  • Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days following each vaccination
  • Concurrent involvement in another clinical trial or planned involvement during the study period
  • Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data or the P. vivax parasite as assessed by the Investigator
  • History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
  • Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine e.g. egg products, Kathon
  • History of allergic disease or reactions likely to be exacerbated by malaria infection.

History of clinically significant contact dermatitis

  • Any history of anaphylaxis in reaction to vaccinations
  • Pregnancy, lactation or intention to become pregnant during the study.
  • Use of medications known to cause prolongation of the QT interval and existing contraindication to the use of Malarone.

Use of medications known to have a potentially clinically significant interaction with Riamet and Malarone.

  • Any clinical condition known to prolong the QT interval.
  • History of cardiac arrhythmia, including clinically relevant bradycardia.
  • Disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia.
  • Family history of congenital QT prolongation or sudden death.
  • Contraindications to the use of both of the proposed anti-malarial medications; Riamet Malarone.
  • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
  • History of serious psychiatric condition that may affect participation in the study.
  • Any other serious chronic illness requiring hospital specialist supervision.
  • Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 25 standard UK units every week.
  • Suspected or known injecting drug abuse in the 5 years preceding enrolment.
  • Hepatitis B surface antigen (HBsAg) detected in serum.
  • Seropositive for hepatitis C virus (antibodies to HCV) at screening or (unless has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV RNA PCR at screening for this study).
  • Positive family history in both 1st AND 2nd degree relatives < 50 years old for cardiac disease.
  • Volunteers unable to be closely followed for social, geographic or psychological reasons.
  • Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. In the event of abnormal test results, confirmatory repeat tests will be requested. Procedures for identifying laboratory values meeting exclusion criteria are shown in SOP VC027.
  • Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
  • Inability of the study team to contact the volunteer's GP to confirm medical history and safety to participate

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04009096


Contacts
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Contact: Volunteer Recruitment Co-ordinator 01865 611424 vaccinetrials@ndm.ox.ac.uk
Contact: Volunteer Recruitment Co-ordinator vaccinetrials@ndm.ox.ac.uk

Locations
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United Kingdom
Centre for Clinical Vaccinology & Tropical Medicine
Oxford, Oxfordshire, United Kingdom, OX3 7LE
Sponsors and Collaborators
University of Oxford
Investigators
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Principal Investigator: Angela M Minassian, MBBS MA DPhil MRCP FRCPath University of Oxford

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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT04009096     History of Changes
Other Study ID Numbers: VAC071
First Posted: July 4, 2019    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Oxford:
PvDBP
efficacy

Additional relevant MeSH terms:
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Malaria
Malaria, Vivax
Protozoan Infections
Parasitic Diseases