A Phase I/IIa Study of the Safety, Immunogenicity and Efficacy of FMP2.1/AS01B, an Asexual Blood-Stage Vaccine for Plasmodium Falciparum Malaria
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Plasmodium Falciparum Malaria
- Sponsor
- University of Oxford
- Enrollment
- 30
- Locations
- 3
- Primary Endpoint
- PCR-derived parasite multiplication rate (PMR)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
The purpose of this study is to evaluate an experimental malaria vaccine for its ability to prevent malaria infection or disease in a blood-stage challenge model (when volunteers are infected with malaria parasites using malaria-infected red blood cells). The vaccine being testing is a protein called FMP2.1, which is given with an adjuvant (a substance to improve the body's response to a vaccination) called AS01B.
The aim is to use this protein and adjuvant to help the body make an immune response against parts of the malaria parasite. This study will enable assessment of:
- The ability of the vaccine to prevent malaria infection.
- The safety of the vaccine in healthy participants.
- The response of the human immune system to the vaccine.
This will be done by giving participants three vaccinations and then exposing them to malaria infection by transfusing a small number of red blood cells infected with malaria under carefully regulated conditions. Participants will be followed closely to observe if and when they develop malaria. If the vaccine provides some protection against malaria, participants will take longer to develop malaria than usual or will not develop malaria at all.
The study will enrol 15 participants to be vaccinated and then challenged with malaria in addition to recruit 15 individuals to be control subjects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy, male or non-pregnant female adults aged 18 - 45 years
- •Subject is willing and able to give written informed consent for participation in the study
- •Resident in or near Oxford for the duration of the challenge part of the study. Or for volunteers not living in Oxford: agreement to stay in arranged accommodation close to the trial centre during a part of the study (from the day before challenge until anti-malarial treatment is completed).
- •Female subjects of child bearing potential must be willing to ensure that they practice continuous effective contraception for the duration of the study
- •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, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines (73).
- •Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of antimalarial treatment.
- •Willingness to take a curative anti-malaria regimen following CHMI.
- •Answer all questions on the informed consent questionnaire correctly.
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).
- •Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data.
- •Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
- •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).
- •Use of immunoglobulins or blood products within 3 months prior to enrolment or previous severe adverse reaction to a blood transfusion.
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (or malaria infection).
- •Any history of anaphylaxis post vaccination.
Outcomes
Primary Outcomes
PCR-derived parasite multiplication rate (PMR)
Time Frame: From the day before CHMI until 23 days after the challenge
PCR-derived parasite multiplication rate (PMR) will be the primary study endpoint, and comparison of the endpoint between the two study groups will constitute the primary analysis for efficacy.