Clinical trial NCT00374998: Safety and Immunogenicity Study of the Malaria Vaccines FP9 PP and MVA PP
Official title: A Phase I Study to Assess the Safety and Immunogenicity of the Polyprotein Malaria Vaccine Candidates FP9 PP and MVA PP in Healthy Adults Using a Prime-Boost Delivery Schedule
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malaria, Falciparum
Malaria
Keywords: Malaria
Vaccine
Prime-boost
Lead sponsor: European Vaccine Initiative
Sponsor class: OTHER
Collaborators: name: University of Oxford
name: Wellcome Trust
First posted: 2006-09-12
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study examines two new malaria vaccines (FP9-PP and MVA-PP) in healthy human volunteers to determine their safety and ability to induce a measurable immune response against malaria.

Detailed description: Malaria infection kills over 2 million people each year. It is a major problem for those who live in endemic areas and for travellers. There is clearly a great need for a safe effective malaria vaccine.

The purpose of this study is to test two candidate malaria vaccines (FP9-PP and MVA-PP) in different concentrations and combinations. These live viral vectors encode a 'polyprotein' of six fused malaria antigens expressed at liver and blood stages of the malaria parasite lifecycle. MVA-PP uses the Modified Virus Ankara vector, a weakened form of the smallpox vaccine, vaccinia. FP9-PP uses a highly attenuated avian pox virus (FP9) as the vector instead. The two vaccines will be used in combination in a 'prime boost' strategy to enhance the response of the cellular immune system.

This study will:

1. Examine safety
2. Examine immunogenicity
3. Provide a subgroup of vaccinated volunteers to test clinical efficacy in the following malaria challenge study (VAC027.2)

Eligibility criteria: Inclusion Criteria:

* Healthy adults aged 18 to 50 years
* Resident in or near Oxford, UK for the duration of the vaccination study
* Willingness to allow the investigators to access hospital and General Practitioner medical notes
* For females only, willingness to practice continuous effective contraception during the study and if participating, during the subsequent challenge study.
* Agreement to refrain from blood donation during the course of the study
* Written informed consent
* Willingness to undergo an HIV test

Exclusion Criteria:

* Any deviation from the protocol-defined normal range in biochemistry or haematology blood tests or in urine analysis
* Prior receipt of an investigational malaria vaccine
* Use of any investigational or non-registered drug, vaccine or medical device other than the study vaccine within 30 days preceding dosing of study vaccine, or planned use during the study period
* Administration of chronic immunosuppressive drugs or other immune modifying drugs within six months of vaccination
* 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
* Any history of malaria
* Travel to a malaria endemic country within the previous 6 months prior to the planned challenge
* Planned travel to malarious areas during the study period
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection and asplenia
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
* Evidence of cardiovascular disease
* History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
* History of haemoglobinopathies
* History of diabetes mellitus
* Chronic or active neurological disease
* Chronic gastrointestinal disease
* History of more than 2 hospitalisations for invasive bacterial infections
* Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
* Seropositive for hepatitis B surface antigen (HBsAg)
* Seropositive for hepatitis C virus (antibodies to HCV)
* Hepatomegaly, right upper quadrant abdominal pain or tenderness
* Evidence of serious psychiatric condition
* Any other on-going chronic illness requiring hospital specialist supervision

Primary outcomes:
measure: Immediate reactogenicity
measure: Adverse events occurring before the end of the trial
measure: Biological safety (haematological and biochemical indices)
Secondary outcomes:
measure: T-cell immunogenicity (prime-boost groups)
measure: Humoral immunogenicity (prime-boost groups)
measure: Gene expression (prime-boost groups)
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford
Study officials:
affiliation: University of Oxford
name: Adrian VS Hill, MA, BM BCh, DPhil, DM
role: PRINCIPAL_INVESTIGATOR
References: