A Study of AdCh63 AMA1 Alone and With MVA AMA1

• Sponsor: University of Oxford
• Information provided by: University of Oxford

Study Description

Brief Summary:

This is an open label phase I study, to assess the safety of a novel malaria vaccine, AdCh63 AMA1, simian adenovirus encoding Plasmodium falciparum blood stage antigen, Apical Membrane Antigen -1. All volunteers recruited will be healthy adults. They will be primed with various doses of AdCh63 AMA1 administered intramuscularly. Some of the volunteers will receive a booster vaccination with MVA AMA1 administered via intramuscular route. Safety data will be collected for each of the eight regimens. Secondary aims of this study will be to assess the immune responses generated by each of these regimes.

Condition or disease	Intervention/treatment	Phase
Malaria	Biological: AdCh63 AMA1; Biological: AdCh63 AMa1 and MVA AMA1	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: March 2010
• Actual Primary Completion Date: October 2010
• Actual Study Completion Date: October 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1; AdCh63 AMA1	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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

Healthy adults aged 18 to 50 years

• Able and willing (in the Investigator's opinion) to comply with all study requirements
• Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner
• For females only, willingness to practice continuous effective barrier contraception during the study and a negative pregnancy test on the day(s) of vaccination
• For males only to use barrier contraception until three months after the last vaccination
• Agreement to refrain from blood donation during the course of the study
• Written informed consent

Exclusion Criteria:

Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period

• Prior receipt of a recombinant adenoviral vaccine.
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
• 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)
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products, Kathon.
• History of clinically significant contact dermatitis
• Any history of anaphylaxis in reaction to vaccination
• Pregnancy, lactation or willingness/intention to become pregnant during the study
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
• History of serious psychiatric condition
• Any other serious chronic illness requiring hospital specialist supervision
• Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
• Suspected or known injecting drug abuse
• Seropositive for hepatitis B surface antigen (HBsAg)
• Seropositive for hepatitis C virus (antibodies to HCV)
• Any other significant disease, disorder or finding, which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer's ability to participate in the study.
• Any history of malaria or
• Travel to a malaria endemic region during the study period or within the previous six months
• Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis
• Any other finding which in the opinion of the investigators would significantly increase the risk of having an adverse outcome from participating in the protocol.

Contacts and Locations

Locations

United Kingdom

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

Sponsors and Collaborators

University of Oxford

Investigators

• Principal Investigator: Adrian VS Hill; Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Churchill Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sheehy SH, Duncan CJ, Elias SC, Biswas S, Collins KA, O'Hara GA, Halstead FD, Ewer KJ, Mahungu T, Spencer AJ, Miura K, Poulton ID, Dicks MD, Edwards NJ, Berrie E, Moyle S, Colloca S, Cortese R, Gantlett K, Long CA, Lawrie AM, Gilbert SC, Doherty T, Nicosia A, Hill AV, Draper SJ. Phase Ia clinical evaluation of the safety and immunogenicity of the Plasmodium falciparum blood-stage antigen AMA1 in ChAd63 and MVA vaccine vectors. PLoS One. 2012;7(2):e31208. doi: 10.1371/journal.pone.0031208. Epub 2012 Feb 21.

• Responsible Party: Prof Adrian Hill, University of Oxford
• ClinicalTrials.gov Identifier: NCT01095055 History of Changes
• Other Study ID Numbers: VAC036
• First Posted: March 29, 2010
• Last Update Posted: March 28, 2011
• Last Verified: March 2011

Additional relevant MeSH terms:

Malaria; Protozoan Infections; Parasitic Diseases