A Phase I/IIa Sporozoite Challenge Study to Assess the Efficacy of Candidate Combination Malaria Vaccine Approaches Using the ChAd63 and MVA Vectors Encoding the Antigens ME-TRAP, CS and AMA1

NCT ID: NCT01739036

Last Updated: 2013-11-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-31

Study Completion Date

2013-10-31

Brief Summary

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This is an open label, multi-centre phase I/IIa sporozoite-challenge trial to assess the safety, immunogenicity and efficacy of two combination ChAd63-MVA heterologous prime-boost vaccination regimens. All volunteers recruited will be healthy, malaria naïve adults aged between 18 and 45 years.

To determine the efficacy of each of two combinations of heterologous prime-boost immunisation strategies:

1. ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS
2. ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS and ChAd63-MVA AMA1

The study will be conducted at the University of Oxford's Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford, UK and the Wellcome Trust Clinical Research Facility in Southampton, UK. The malaria challenge will take place at the insectary at Imperial College (Infection and Immunity Section) in London, UK.

Detailed Description

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Conditions

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Plasmodium Falciparum Malaria

Keywords

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Malaria Vaccine Plasmodium Falciparum

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Group 4

Unvaccinated control volunteers who undergo controlled human malaria infection.

Group Type ACTIVE_COMPARATOR

Controlled Human Malaria Infection Administered by Mosquito Bite

Intervention Type OTHER

Approximately three weeks post MVA dosing.

Group 3

Controlled human malaria infection administered at an interval of approximately 8-12 months after the initial controlled human malaria infection that the volunteers received in the VAC045 clinical trial.

Group Type ACTIVE_COMPARATOR

Controlled Human Malaria Infection Administered by Mosquito Bite

Intervention Type OTHER

Approximately three weeks post MVA dosing.

Group 2

Intramuscular administration of a mixture of ChAd63 ME-TRAP 5 x 1010 vp and ChAd63 CS 5 x 1010 vp and ChAd63 AMA1 5 x 1010 vp followed by intramuscular administration of a mixture of MVA ME-TRAP 1.33 x 108 pfu and MVA CS 1.33 x 108 pfu and MVA AMA1 1.33 x 108 pfu eight weeks later, followed by controlled human malaria infection 17-24 days later.

Group Type ACTIVE_COMPARATOR

ChAd63 CS/ME-TRAP/AMA1

Intervention Type BIOLOGICAL

Mixture of ChAd63 CS 5 x 1010 vp, ChAd63 ME-TRAP 5 x 1010 vp, and ChAd63 AMA1 5 x 1010 vp. Intramuscular needle injection.

MVA CS/ME-TRAP/AMA1

Intervention Type BIOLOGICAL

Mixture of MVA CS 1.33 x 108 pfu, MVA ME-TRAP 1.33 x 108 pfu, and MVA AMA1 1.33 x 108 pfu. Intramuscular needle injection.

Controlled Human Malaria Infection Administered by Mosquito Bite

Intervention Type OTHER

Approximately three weeks post MVA dosing.

Group 1

Intramuscular administration of a mixture of ChAd63 ME-TRAP 5 x 1010 vp and ChAd63 CS 5 x 1010 vp, followed by intramuscular administration of a mixture of MVA ME-TRAP 2 x 108 pfu and MVA CS 2 x 108 pfu eight weeks later, followed by controlled human malaria infection 17-24 days later.

Group Type ACTIVE_COMPARATOR

ChAd63 CS/ME-TRAP

Intervention Type BIOLOGICAL

Mixture of ChAd63 CS 5 x 1010 vp and ChAd63 ME-TRAP 5 x 1010 vp. Intramuscular needle injection.

MVA CS/ME-TRAP

Intervention Type BIOLOGICAL

Mixture of MVA CS 2 x 108 pfu and MVA ME-TRAP 2 x 108 pfu. Intramuscular needle injection.

Controlled Human Malaria Infection Administered by Mosquito Bite

Intervention Type OTHER

Approximately three weeks post MVA dosing.

Interventions

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ChAd63 CS/ME-TRAP

Mixture of ChAd63 CS 5 x 1010 vp and ChAd63 ME-TRAP 5 x 1010 vp. Intramuscular needle injection.

Intervention Type BIOLOGICAL

MVA CS/ME-TRAP

Mixture of MVA CS 2 x 108 pfu and MVA ME-TRAP 2 x 108 pfu. Intramuscular needle injection.

Intervention Type BIOLOGICAL

ChAd63 CS/ME-TRAP/AMA1

Mixture of ChAd63 CS 5 x 1010 vp, ChAd63 ME-TRAP 5 x 1010 vp, and ChAd63 AMA1 5 x 1010 vp. Intramuscular needle injection.

Intervention Type BIOLOGICAL

MVA CS/ME-TRAP/AMA1

Mixture of MVA CS 1.33 x 108 pfu, MVA ME-TRAP 1.33 x 108 pfu, and MVA AMA1 1.33 x 108 pfu. Intramuscular needle injection.

Intervention Type BIOLOGICAL

Controlled Human Malaria Infection Administered by Mosquito Bite

Approximately three weeks post MVA dosing.

Intervention Type OTHER

Eligibility Criteria

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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.
* Women only: Must practice continuous effective contraception for the duration of the study.
* 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.
* Written informed consent to participate in the trial.
* Reachable (24/7) by mobile phone during the period between CHMI and completion of antimalarial treatment.
* 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.
* Group 3 volunteers only: have been sterilely protected against malaria following CHMI after receiving ChAd63-MVA prime-boost vaccination in the VAC045 clinical trial

Exclusion Criteria

* History of clinical malaria (any species).
* Travel to a malaria endemic region during the study period or within the preceding six months with significant risk of malaria exposure.
* Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
* Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
* Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data. For Group 3 participants, and Group 1 and 2 participants undergoing rechallenge, this exclusion criterion does not extend to the vaccines previously received for the VAC045 and VAC052 trials.
* 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.
* History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
* Pregnancy, lactation or intention to become pregnant during the study.
* Use of medications known to cause prolongation of the QT interval or to otherwise have a potentially clinically significant interaction with Riamet
* Any clinical condition known to prolong the QT interval
* History of cardiac arrhythmia, including clinically relevant bradycardia
* Disturbances of electrolyte balance, eg, hypokalaemia or hypomagnesaemia
* Family history of congenital QT prolongation or sudden death
* Contraindications to the use of all three proposed anti-malarial medications; Riamet, Malarone and Chloroquine.
* 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 units every week.
* Suspected or known injecting drug abuse in the 5 years preceding enrolment.
* Seropositive for hepatitis B surface antigen (HBsAg).
* Seropositive for hepatitis C virus (antibodies to HCV) with positive PCR for hepatitis C at screening.
* An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system.76
* Positive family history in 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.
* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adrian V S Hill, MD

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Locations

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Wellcome Trust CRF, Southampton General Hospital

Southampton, Hampshire, United Kingdom

Site Status

Centre for Clinical Vaccinology and Tropical Medicine

Oxford, Oxfordshire, United Kingdom

Site Status

Infection and Immunity Section, Imperial College of Science, Technology and Medicine

London, , United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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VAC052

Identifier Type: -

Identifier Source: org_study_id