A Study of AdCh63 AMA1 Alone and With MVA AMA1
|Malaria||Biological: AdCh63 AMA1 Biological: AdCh63 AMa1 and MVA AMA1||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Phase I Study to Assess the Safety and Immunogenicity of New Malaria Vaccine Candidates AdCh63 AMA1 Alone and With MVA AMA1|
- Safety of AdCh63 administered alone, and combinedwith MVA AMA1 [ Time Frame: Up to 6 months following the last vaccination ]To assess the safety in healthy volunteers of two candidate malaria vaccines, AdCh63 AMA1 with MVA AMA1 in a prime-boost regimen. The safety of AdCh63 administered alone, and combined with MVA AMA1 will be assessed. The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events.
- The level of immune response induced by vaccination with AdCh63 AMA1, when administered as a single vaccination and sequentially with MVA AMA1 [ Time Frame: Up to 6 moths following the last vaccination ]To assess the level of immune response induced by vaccination with AdCh63 AMA1, when administered as a single vaccination and sequentially with MVA AMA1
|Study Start Date:||March 2010|
|Study Completion Date:||October 2010|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
Experimental: Group 1
Biological: AdCh63 AMA1
Group 1A - single dose of AdCH63 AMA1 5x10^9 vp intramuscularly Group 2A - single dose of AdCH63 AMA1 5x10^10 vp intramuscularly
Other Name: Simian adenovirus expressing malaria antigen AMA1
Experimental: Group 2
AdCh63 AMA1 followed by MVA AMA1
Biological: AdCh63 AMa1 and MVA AMA1
Group 1B - single dose of AdCH63 AMA1 5x10^9 vp intramuscularly and single dose of MVA AMA1 5x10^8 pfu 8 weeks later intramuscularly Group 2B - single dose of AdCH63 AMA1 5x10^10 vp intramuscularly and single dose of MVA AMA1 5x10^8 pfu 8 weeks later intramuscularly
Other Name: Simian adenovirus, modified vaccinia Ankara virus expressing malaria antigen AMA1
AMA1 is a type I integral membrane protein. It is produced by mature P. falciparum schizonts in infected erythrocytes AMA1 has become a leading candidate vaccine antigen. This is based on several facts, most notably that in several field studies an association was found between antibodies to the ectodomain of AMA1 and protection against clinical malaria. Also, in the Gambia, presence of antibodies to AMA1 and MSP-1 has been shown to enhance clearance of chloroquine resistant parasites in vivo.
There are a number of trials currently ongoing in Oxford which are aimed at examining a simian adenovirus as a delivery vehicle and liver and blood stage malaria antigens as inserts. AdCh63 is currently in use with the MSP-1 insert, a blood stage antigen, in a phase I dose escalation clinical trial in Oxford (VAC037 / GTAC 166). The trial design includes AdCh63 MSP-1 administered alone and with MVA MSP-1 as part of a heterologous prime boost schedule, with sporozoite challenge of 3 volunteers in the higher dose group. At the most recent interim analysis, AdCh63 MSP-1 demonstrates an excellent safety profile.
Also, AdCh63 is currently in use with the ME-TRAP insert, a liver stage antigen in a phase I dose escalation clinical trial in Oxford, (VAC033 / GTAC133) and a phase I/IIa trial with sporozoite challenge (MAL034 / OXREC: 09/H064/9). AdCh63 ME-TRAP has been administered alone and with MVA ME-TRAP as part of a heterologous prime boost schedule at various doses with excellent safety and immunogenicity to 87 volunteers at time of interim analysis.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01095055
|Hospital for Tropical Diseases|
|London, United Kingdom, WC1E 6JB|
|Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Old Road, Headington|
|Oxford, United Kingdom, OX3 7LJ|
|Principal Investigator:||Adrian VS Hill||Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Churchill Hospital|