Study to Assess Efficacy of New Malaria Vaccine Candidates AdCh63 AMA1, MVA AMA1, AdCh63 MSP1, MVA MSP1, AdCh63 ME-TRAP & MVA ME-TRAP

NCT01142765 | Completed Phase 1 DMC

• 1 other identifier: VAC039
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 3

Brief Summary

This study aims to test the safety and efficacy of six new malaria vaccines - AdCh63 AMA1, MVA AMA1, AdCh63 MSP1, MVA MSP1, AdCh63 ME-TRAP \& MVA ME-TRAP. These vaccines consist of inactivated viruses which have been modified - so they cannot reproduce (replicate) in humans, and also to include genetic material (genes) for malaria proteins which are expressed by the malaria parasite during both liver and blood stage infection. The vaccines are designed to stimulate an immune response to these malaria proteins (immunogenicity describes the nature and magnitude of this immune response) and thus provide protection against malaria infection. The protective efficacy of vaccines will be evaluated by challenging a small number of volunteers who have received the vaccines with malaria infection from the bites of infected mosquitos(sporozoite challenge).

Conditions

Malaria

Keywords

Vaccine; Safety; Immunogenicity; Protection; Sporozoite challenge

Outcome Measures

Primary Outcomes (1)

• Safety and efficacy of vaccine

  To assess if volunteers who receive the novel vaccine candidates; AdCh63 MSP1, MVA MSP1, AdCh63 AMA1, MVA AMA1, AdCh63 ME-TRAP and MVA ME-TRAP in heterologous prime boost regimens are protected wholly or partially against malaria infection in a sporozoite challenge model. This will be determined by noting the number of subjects who develop malaria infection and the time in hours between exposure and parasitaemia as detected by thick-film blood smear compared with controls. To assess the safety of the immunisation regimens alone and during co-administration.

  Up to 18 months

Secondary Outcomes (1)

• Immunogenicity of vaccine

  Up to 18 months

Study Arms (5)

Group 1

EXPERIMENTAL

1 dose of AdCh63 MSP1 and 1 dose MVA MSP1 followed by sporozoite challenge

Biological: AdCh63 MSP1, MVA MSP1, challenge

Group 2

EXPERIMENTAL

1 dose of AdCh63 AMA1 and 1 dose MVA AMA1 followed by sporozoite challenge

Biological: AdCh63 AMA1, MVA AMA1, challenge

Group 3

EXPERIMENTAL

1 dose of AdCh63 AMA1 and 1 dose AdCh63 MSP1 co-administered into separate arms followed by 1 dose of MVA AMA1 and 1 dose MVA MSP1 co-administered into separate arms (but the same arm as the corresponding AdCh63 vaccine) followed by sporozoite challenge

Biological: AdCh63 AMA1, AdCh63 MSP1, MVA AMA1, MVA MSP1, challenge

Group 4

EXPERIMENTAL

1 dose of AdCh63 MSP1 and 1 dose AdCh63 ME-TRAP co-administered into separate arms followed by 1 dose of MVA MSP1 and 1 dose MVA ME-TRAP co-administered into separate arms (but the same arm as the corresponding AdCh63 vaccine) followed by sporozoite challenge

Biological: AdCh63 MSP1, AdCh63 ME-TRAP, MVA MSP1, MVA ME-TRAP, challenge

Group 5

OTHER

Non-vaccinated controls for sporozoite challenge

Biological: Sporozoite challenge

Interventions

AdCh63 MSP1, MVA MSP1, challenge BIOLOGICAL

1 dose of AdCh63 MSP1 5 x 1010 vp intramuscularly and 1 dose MVA MSP1 2.5 x 108 pfu intramuscularly 8 weeks later (range 6-12 weeks) followed by sporozoite challenge 12-28 days later

Group 1

AdCh63 AMA1, MVA AMA1, challenge BIOLOGICAL

1 dose of AdCh63 AMA1 5 x 1010 vp intramuscularly and 1 dose MVA AMA1 2.5 x 108 pfu intramuscularly 8 weeks later (range 6-12 weeks) followed by sporozoite challenge 12-28 days later

Group 2

AdCh63 AMA1, AdCh63 MSP1, MVA AMA1, MVA MSP1, challenge BIOLOGICAL

1 dose of AdCh63 AMA1 5 x 1010 vp intramuscularly and 1 dose AdCh63 MSP1 5 x 1010 vp intramuscularly co-administered into separate arms followed 8 weeks later (range 6-12 weeks) by 1 dose of MVA AMA1 2.5 x 108 pfu intramuscularly and 1 dose MVA MSP1 2.5 x 108 pfu intramuscularly co-administered into separate arms (but the same arm as the corresponding AdCh63 vaccine) followed by sporozoite challenge 12-28 days later.

Group 3

AdCh63 MSP1, AdCh63 ME-TRAP, MVA MSP1, MVA ME-TRAP, challenge BIOLOGICAL

1 dose of AdCh63 MSP1 5 x 1010 vp intramuscularly and 1 dose AdCh63 ME-TRAP 5 x 1010 vp intramuscularly co-administered into separate arms followed 8 weeks later (range 6-12 weeks) by 1 dose of MVA MSP1 2.5 x 108 pfu intramuscularly and 1 dose MVA ME-TRAP 2 x 108 pfu intramuscularly co-administered into separate arms (but the same arm as the corresponding AdCh63 vaccine) followed by sporozoite challenge 12-28 days later.

Group 4

Sporozoite challenge BIOLOGICAL

Non-vaccinated controls for sporozoite challenge

Group 5

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 female volunteers, willingness to practice continuous effective contraception for the duration of the study.
• Agreement to refrain from blood donation during the course of the study
• Written informed consent

You may not qualify if:

• History of clinical P. falciparum malaria
• Travel to a malaria endemic region during the study period or within the preceding six months with a risk of malaria exposure.
• 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 an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data
• 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)
• Pregnancy, lactation or intention to become pregnant during the study
• Contraindication to both anti-malarial drugs; Riamet \& chloroquine
• Concomitant use with other drugs known to cause QT-interval prolongation (e.g. macrolides, quinolones, amiodarone etc)
• History of epilepsy
• History of arrhythmia or prolonged QT interval.
• Family history for sudden cardiac death.
• An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system 107
• 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

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (3)

Hospital for Tropical Diseases Mortimer Market

London, WC1E 6JB, United Kingdom

Location

Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford

Oxford, OX3 7LJ, United Kingdom

Location

Wellcome Trust Clinical Research Facility, University of Southampton

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Adrian VS Hill, D.Phil, FRCP

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 7, 2010
• First Posted: June 11, 2010
• Study Start: June 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: March 28, 2011

Record last verified: 2011-03

Locations

GB (3)