An Efficacy Study of IV Boosting With ChAd63/MVA ME-TRAP

Malaria Clinical Trial

Official title: A Phase I/IIa Sporozoite Challenge Study to Assess the Safety, Immunogenicity and Protective Efficacy of Intravenous Boosting With Malaria Vaccine Candidates ChAd63 and MVA Encoding ME-TRAP

Status Completed

Clinical Trial Summary

Plasmodium falciparum Malaria remains a major global health problem with approximately 200 million cases and 500,000 deaths worldwide annually, mostly in African infants. Current malarial control strategies are threatened by emergence of parasite resistance to drug treatment and resistance of the mosquito vector to certain insecticides. A deployable malaria vaccine is therefore a key strategy for reducing malaria mortality and progressing towards global eradication, but those in clinical trials are currently someway short of WHO targets.

ChAd63 ME-TRAP and MVA ME-TRAP are leading candidate vaccines being developed by Adrian Hill's group at the University of Oxford, and collaborators. Since 2007, testing of these vaccines intramuscularly in over 900 volunteers has shown them to be safe, well tolerated and capable of delivering partial efficacy against malaria infection. This study will be the first time studying the efficacy of giving a boosting dose of the vaccines intravenously in what the investigators call a "prime-target" strategy. It follows very encouraging pre-clinical work showing this route can target desirable immune responses to the liver to fight a crucial stage of malaria infection. An ongoing recent phase I study is dose escalating both these vaccines intravenously as a single dose prior to commencing this trial where intramuscular and intravenous doses will be combined for the first time. The investigators will initially recruit 46 healthy UK adult volunteers who will be enrolled into 4 vaccination arms (10 volunteers each) and an unvaccinated control group (6 volunteers) who will undergo a controlled human malaria infection (CHMI). These are standardised, carefully supervised infection experiments used internationally to assess vaccine efficacy. As this is the first time giving intramuscular and intravenous doses of these vaccines in a combined schedule, the investigators will closely profile the safety and immune response during the vaccination follow-up. All trial activity will take place in Oxford.

Clinical Trial Description

The study is considered of low risk to the health of participants. Volunteers will receive investigational vaccines, be infected with malaria by mosquito bite, may develop clinical malaria disease, will be treated with antimalarial drugs, and will have blood taken regularly. They will also be given the option to undergo a minimally invasive procedure - Fine Needle Aspiration of the liver - to examine the immune response in this target organ which is also considered to be low risk.

As this is the first time intravenous dose of the vaccines following intramuscular prime/boost doses will be administered, once volunteers have received their intramuscular doses the investigators will stagger the intravenous vaccinations to allow for interim safety reviews. The first volunteer in groups 1&2, once they have received their two intramuscular doses, will receive their intravenous vaccine dose alone and observed for a minimum 8 hours. If there have been no concerns identified at the 8 hour and 24 hour reviews identified by the CI and Local Safety Committee (LSC) chair, the next two volunteers in these groups will receive their intravenous vaccine dose. There will be a further safety 24 hours after these volunteers have been vaccinated before the remaining volunteers are vaccinated.

Volunteers are expected to have both vaccine site reactions (eg, pain, swelling, warmth in the arm where the vaccine is given) and systemic reactions to vaccination (eg, fever, headache, tiredness, sore muscles and joints). These are expected to resolve completely within several days, and symptoms strong enough to prevent usual activities over this time are expected to be uncommon. ;

Related Conditions & MeSH terms

• Malaria

• NCT number: NCT03707353
• Study type: Interventional
• Source: University of Oxford
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 30, 2018
• Completion date: June 10, 2019