An Efficacy Study of IV Boosting With ChAd63/MVA ME-TRAP

September 25, 2019 updated by: University of Oxford

A Phase I/IIa Sporozoite Challenge Study to Assess the Safety, Immunogenicity and Protective Efficacy of Intravenous Boosting With Malaria Vaccine Candidates ChAd63 and MVA Encoding ME-TRAP

Plasmodium falciparum Malaria remains a major global health problem with approximately 200 million cases and 500,000 deaths worldwide annually, mostly in African infants. Current malarial control strategies are threatened by emergence of parasite resistance to drug treatment and resistance of the mosquito vector to certain insecticides. A deployable malaria vaccine is therefore a key strategy for reducing malaria mortality and progressing towards global eradication, but those in clinical trials are currently someway short of WHO targets.

ChAd63 ME-TRAP and MVA ME-TRAP are leading candidate vaccines being developed by Adrian Hill's group at the University of Oxford, and collaborators. Since 2007, testing of these vaccines intramuscularly in over 900 volunteers has shown them to be safe, well tolerated and capable of delivering partial efficacy against malaria infection. This study will be the first time studying the efficacy of giving a boosting dose of the vaccines intravenously in what the investigators call a "prime-target" strategy. It follows very encouraging pre-clinical work showing this route can target desirable immune responses to the liver to fight a crucial stage of malaria infection. An ongoing recent phase I study is dose escalating both these vaccines intravenously as a single dose prior to commencing this trial where intramuscular and intravenous doses will be combined for the first time. The investigators will initially recruit 46 healthy UK adult volunteers who will be enrolled into 4 vaccination arms (10 volunteers each) and an unvaccinated control group (6 volunteers) who will undergo a controlled human malaria infection (CHMI). These are standardised, carefully supervised infection experiments used internationally to assess vaccine efficacy. As this is the first time giving intramuscular and intravenous doses of these vaccines in a combined schedule, the investigators will closely profile the safety and immune response during the vaccination follow-up. All trial activity will take place in Oxford.

Study Overview

Status

Status

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

Conditions

Conditions

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

Intervention / Treatment

Intervention / Treatment

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

Detailed Description

The study is considered of low risk to the health of participants. Volunteers will receive investigational vaccines, be infected with malaria by mosquito bite, may develop clinical malaria disease, will be treated with antimalarial drugs, and will have blood taken regularly. They will also be given the option to undergo a minimally invasive procedure - Fine Needle Aspiration of the liver - to examine the immune response in this target organ which is also considered to be low risk.

As this is the first time intravenous dose of the vaccines following intramuscular prime/boost doses will be administered, once volunteers have received their intramuscular doses the investigators will stagger the intravenous vaccinations to allow for interim safety reviews. The first volunteer in groups 1&2, once they have received their two intramuscular doses, will receive their intravenous vaccine dose alone and observed for a minimum 8 hours. If there have been no concerns identified at the 8 hour and 24 hour reviews identified by the CI and Local Safety Committee (LSC) chair, the next two volunteers in these groups will receive their intravenous vaccine dose. There will be a further safety 24 hours after these volunteers have been vaccinated before the remaining volunteers are vaccinated.

Volunteers are expected to have both vaccine site reactions (eg, pain, swelling, warmth in the arm where the vaccine is given) and systemic reactions to vaccination (eg, fever, headache, tiredness, sore muscles and joints). These are expected to resolve completely within several days, and symptoms strong enough to prevent usual activities over this time are expected to be uncommon.

Study Type

Study Type

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

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
43

Phase

Phase

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

Contacts and Locations

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

Study Locations

  • United Kingdom
      • London, United Kingdom, W12 0HS
        • NIHR Clinical Research Facility, Hammersmith Hospital
      • Oxford, United Kingdom, OX3 9DU
        • John Radcliffe Hospital
      • Oxford, United Kingdom, OX3 7LE
        • CCVTM, University of Oxford
      • Southampton, United Kingdom, SO16 6YD
        • Southampton National Institute for Health Research

Participation Criteria

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

Eligibility Criteria

Eligibility Criteria

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

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy adults aged 18 to 45 years
  • 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
  • For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and vaccination
  • Agreement to refrain from blood donation during the course of the study
  • Provide written informed consent to participate in the trial.
  • Agreement to refrain from blood donation during the course of the study and for at least 3 years after the end of their involvement in the study.
  • Reachable (24/7) by mobile phone during the period between CHMI and completion of antimalarial treatment.
  • Willingness to provide a named person who may be contacted in the event it is not possible to locate the volunteer following CHMI
  • Willingness to take a curative anti-malaria regimen following CHMI.
  • For volunteers not living in Oxford: agreement to stay in a hotel room close to the trial centre during a part of the study (from at least day 6.5 post mosquito bite until anti-malarial treatment is completed).
  • Answer all questions on the informed consent quiz correctly.

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
  • Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
  • Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data as assessed by the investigator. This may include non-malaria adenovirus vectored experimental vaccine. If any volunteers undergo rechallenge, this exclusion criterion does not extend to the vaccines previously received in the VAC066 trial.
  • 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).
  • Use of immunoglobulins or blood products within 3 months prior to enrolment. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (e.g. egg products, Kathon) or malaria infection.
  • Any history of anaphylaxis post vaccination.
  • History of clinically significant contact dermatitis.
  • Pregnancy, lactation or intention to become pregnant during the study.
  • 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 42 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 (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).
  • Inability of the study team to contact the volunteer's GP to confirm medical history and safety to participate
  • 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 (described in section 9.6.1).
  • 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.
  • Clinically significant disturbances of electrolyte balance, eg, hypokalaemia or hypomagnesaemia
  • Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin).
  • History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
  • 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.
  • Contraindications to the use of both Riamet and Malarone.
  • Any clinical condition known to prolong the QT interval and existing contraindication to the use of Malarone.

Family history of congenital QT prolongation or sudden death and existing contraindication to the use of Malarone.

  • History of cardiac arrhythmia, including clinically relevant bradycardia and existing contraindication to the use of Malarone.
  • Positive family history in both 1st and 2nd degree relatives < 50 years old for cardiac disease.
  • Volunteer unable to be closely followed for social, geographic or psychological reason.

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

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

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Group 1
Volunteers will receive ChAd63 ME-TRAP vaccination intramuscularly, then MVA ME-TRAP vaccination intramuscularly followed by ChAd63 ME-TRAP vaccination intravenously.
Biological: ChAd63 ME-TRAP and MVA ME-TRAP vaccination
vaccination with ChAd63 ME-TRAP 5x10^10 vp (intramuscularly and intravenously) vaccination with MVA METRAP 2x10^8 pfu (intramuscularly) and MVA METRAP 2x10^7 pfu (intravenously) Group 5 will be challenged with malaria by mosquito bite.
Experimental: Group 2
Volunteers will receive ChAd63 ME-TRAP vaccination intramuscularly, then MVA ME-TRAP vaccination intramuscularly followed by MVA ME-TRAP vaccination intravenously.
Biological: ChAd63 ME-TRAP and MVA ME-TRAP vaccination
vaccination with ChAd63 ME-TRAP 5x10^10 vp (intramuscularly and intravenously) vaccination with MVA METRAP 2x10^8 pfu (intramuscularly) and MVA METRAP 2x10^7 pfu (intravenously) Group 5 will be challenged with malaria by mosquito bite.
Experimental: Group 3
Volunteers will receive ChAd63 ME-TRAP vaccination intramuscularly, followed by ChAd63 ME-TRAP vaccination intravenously.
Biological: ChAd63 ME-TRAP and MVA ME-TRAP vaccination
vaccination with ChAd63 ME-TRAP 5x10^10 vp (intramuscularly and intravenously) vaccination with MVA METRAP 2x10^8 pfu (intramuscularly) and MVA METRAP 2x10^7 pfu (intravenously) Group 5 will be challenged with malaria by mosquito bite.
Experimental: Group 4
Volunteers will receive ChAd63 ME-TRAP vaccination intramuscularly, followed by MVA ME-TRAP vaccination intravenously. 4 weeks after the last vaccine dose, all vaccinated volunteers will undergo malaria challenge by mosquito bite.
Biological: ChAd63 ME-TRAP and MVA ME-TRAP vaccination
vaccination with ChAd63 ME-TRAP 5x10^10 vp (intramuscularly and intravenously) vaccination with MVA METRAP 2x10^8 pfu (intramuscularly) and MVA METRAP 2x10^7 pfu (intravenously) Group 5 will be challenged with malaria by mosquito bite.
No Intervention: Group 5
6 Volunteers will receive no vaccinations but will undergo malaria challenge infection by mosquito bite at the same time as groups 1-4.
No Intervention: Group 6
6 Volunteers will be used as infectivity controls if any volunteers from Groups 1-4 are rechallenged 5 - 7 months after the initial CHMI.
Experimental: Group A
Volunteers will receive ChAd63 ME-TRAP vaccination intramuscularly, then MVA ME-TRAP vaccination intramuscularly followed by MVA ME-TRAP vaccination intravenously.
Biological: ChAd63 ME-TRAP and MVA ME-TRAP vaccination
vaccination with ChAd63 ME-TRAP 5x10^10 vp (intramuscularly and intravenously) vaccination with MVA METRAP 2x10^8 pfu (intramuscularly) and MVA METRAP 2x10^7 pfu (intravenously) Group 5 will be challenged with malaria by mosquito bite.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Efficacy and safety of intramuscular vaccination followed by intravenous boosting with ChAd63 and MVA encoding ME-TRAP, in healthy malaria-naïve volunteers, assessed by frequency of adverse events
Time Frame: Solicited and Unsolicited AEs will be collected for 28 days. SAEs will be collected from enrolment until the end of the follow-up period (16 weeks following completion of the prime target regimen)
Occurrence of solicited and unsolicited local and systemic adverse events
Solicited and Unsolicited AEs will be collected for 28 days. SAEs will be collected from enrolment until the end of the follow-up period (16 weeks following completion of the prime target regimen)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To assess cell-mediated immunogenicity generated in malaria naïve individuals of vaccination schedules incorporating intramuscular prime dose(s) followed by intravenous booster with ChAd63 and MVA encoding ME-TRAP.
Time Frame: Up to 11-13 months from initial vaccination
The key measure of immunogenicity will be ELISPOT to enumerate IFN-γ producing T cells.
Up to 11-13 months from initial vaccination

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Oxford

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Adrian V Hill, DPhill FRCP, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK

Study record dates

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

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 30, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 10, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 10, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 10, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 15, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 16, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 26, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VAC066

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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

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