A Study to Assess Safety, Immunogenicity and Parasite Growth Inhibition of an Asexual Blood Stage Vaccine for P. Falciparum Malaria

University of Oxford

Status and phase

Completed

Phase 2

Phase 1

Conditions

Malaria

Treatments

Biological: AMA1-C1/Alhydrogel® + CPG 7909

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00984763

VAC035

Details and patient eligibility

About

Malaria is a parasite, infection with which kills over 2 million people each year. It is a major problem for those who live in endemic areas and for travellers. There is a great need for a safe effective malaria vaccine. The purpose of this study is to examine a new vaccine designed to provide immunity during the blood stage of the malaria parasite's lifecycle.

The vaccine consists of AMA1-C1 which is a mixture of two recombinant synthetic AMA1 proteins from two Plasmodium falciparum strains, Alhydrogel® which is an aluminium-based adjuvant and CPG 7909 - an oligodeoxynucleotide, which enhances immune response.

This study will enable the investigators to assess:

The ability of of a growth inhibition assay to predict the effectiveness of a malaria vaccine.
The safety of the vaccine in healthy volunteers
The response of the human immune system to the vaccine

Enrollment

8 patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Subject is willing and able to give informed consent for participation in the study
Healthy, non pregnant adult aged 18 - 50 years
Resident in or near Oxford for the duration of the challenge study
Seropositive for CMV and EBV
Female subjects of child bearing potential must be willing to ensure that they practice effective contraception during the study
Males must be willing to use barrier contraception from day of first vaccination onwards until 3 months after the second vaccination
Able (in the Investigator's opinion) and willing to comply with all study requirements
Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study
Agreement to permanently refrain from blood donation.

Exclusion criteria

Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis as defined in Appendix B
Female patient/subject who is pregnant, lactating or planning pregnancy during the course of the study
Healthy volunteers who have participated in another research study involving an investigational product in the past 12 weeks
Subjects who have previously received an investigational malaria vaccine
History of malaria chemoprophylaxis with chloroquine within 5 months prior to the planned challenge, with Lariam within 6 weeks prior to the challenge, and Riamet® within 2 weeks prior to the challenge
Travel to a malaria endemic area within the previous 6 months
Planned travel to malarious areas during the study period
Any history of malaria
Contraindication to both anti-malarial drugs (Riamet® and chloroquine)
concomitant use of other drugs known to cause QT-interval prolongation, ( e.g. macrolides, quinolones, amiodarone etc)
An estimated ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system (Conroy 2003)
Family history of sudden cardiac death
History of cardiac arrhythmia or prolonged QT syndrome
Any history of severe allergic reaction or anaphylaxis
History of a known allergy to nickel
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
History or evidence of pre-existing autoimmune or antibody mediated disease or laboratory evidence of possible autoimmune disease (defined as anti-dsDNA ≥ 25 IU/mL)
Seropositive for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis C virus
Any on-going chronic illness requiring hospital specialist supervision
Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
History of or current intravenous drug abuse
Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
Any other significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or may influence the result of the study, or the subject's ability to participate in the study.
Investigator assessment of lack of willingness to participate and comply with all requirements of the protocol