A Study of AdCh63 ME-TRAP Alone and With MVA ME-TRAP

University of Oxford

Status and phase

Completed

Phase 1

Conditions

Malaria

Treatments

Biological: AdCh63 ME-TRAP; MVA ME-TRAP

Biological: AdCh63 ME-TRAP

Study type

Interventional

Funder types

Other

Identifiers

NCT00890019

VAC033

Details and patient eligibility

About

This is an open label phase I study, to assess the safety of a novel malaria vaccine, AdCh63 ME-TRAP, simian adenovirus encoding Plasmodium falciparum antigens. This follows promising phase I clinical studies of MVA ME-TRAP and preclinical studies of AdCh63 and MVA ME-TRAP used together in prime-boost regimes. All volunteers recruited will be healthy adults. They will be primed with various doses of AdCh63 ME-TRAP administered intradermally or intramuscularly. Some of the volunteers will receive a booster vaccination with MVA ME-TRAP at various doses administered via the intradermal or intramuscular route. Safety data will be collected for each of the eight regimens. Secondary aims of this study will be to assess the immune responses generated by each of these regimes.

Full description

ME-TRAP insert contains a fusion protein of multiple epitopes (ME) and the Plasmodium falciparum pre-erythrocytic thrombospondin-related adhesion protein (TRAP). The 'ME' is a string of 20 epitopes fused to the thrombospondin-related adhesion protein. TRAP was selected as it is well characterized and has a protective homologue in rodents. We have safely administered ME-TRAP to over 700 volunteers in the UK and Africa.

MVA vector proved to be non-contagious and avirulent. Viral replication is blocked late during infection of cells but importantly viral and recombinant protein synthesis is unimpaired even during this abortive infection. Replication-deficient recombinant MVA has been viewed as an exceptionally safe viral vector. When tested in animal model studies recombinant MVAs have been shown to be avirulent, yet protectively immunogenic as vaccines against viral diseases and cancer. Recent studies in macaques severely immuno-suppressed by SIV infection have further supported the view that MVA should be safe in immuno-compromised humans.

Simian adenoviruses have not been used previously in a clinical trial in humans. However, they are under active development as vaccines for HIV, (by GSK), and for HCV, (Merck).

Enrollment

54 patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy adults aged 18 to 50 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
Willing to use barrier contraception until three months after the last vaccination
For females only negative pregnancy test on the day(s) of vaccination
Agreement to refrain from blood donation during the course of the study
Written informed consent

Exclusion criteria

Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period
Prior receipt of a recombinant MVA vaccine containing a relevant antigen (for those in B groups) or adenoviral vaccine, (all volunteers).
Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
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 clinically significant contact dermatitis
Any history of anaphylaxis in reaction to vaccination
History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
History of serious psychiatric condition
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
Seropositive for hepatitis B surface antigen (HBsAg)
Seropositive for hepatitis C virus (antibodies to HCV)
Seropositive for simian adenovirus 63 (antibodies to AdCh63) at a titre >1 ;200
Pregnancy, lactation or willingness/intention to become pregnant during the study
Any other significant disease, disorder or finding, which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer's ability to participate in the study.
Any history of malaria or
Travel to a malaria endemic region during the study period or within the previous six months
Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis
Any other finding which in the opinion of the investigators would significantly increase the risk of having an adverse outcome from participating in the protocol.