A Study of the Safety and Effectiveness of Two New Malaria Vaccines

NCT01003314 | Completed Phase 1 DMC

• 1 other identifier: VAC037
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to test the safety of two new malaria vaccines AdCh63 MSP1 and MVA MSP1. 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 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), to provide protection against malaria infection. This protection has been demonstrated in nonhuman studies. Although these vaccines have not been given to humans before, similar vaccines using the same viruses with different malaria genes have been given to humans before. In these studies, the vaccines have been shown to be safe. They have also provided evidence from laboratory tests of immunogenicity. In this study the investigators main aim is to ensure these new vaccines given alone and in combination are safe. The investigators will increase the dose of the first vaccine (AdCh63 MSP1) given to volunteers if the initial dose is safe. The investigators also wish to ensure that challenging a small number of volunteers who have received both vaccines with malaria infection from the bites of infected mosquitos(sporozoite challenge) is safe. Sporozoite challenge has been widely used in humans to test the effectiveness of malaria vaccines and is considered a well established, reliable, predictable and safe system.In the study the investigators will also look for evidence of immunogenicity of these new vaccines, and whether there is any delay to developing malaria following sporozoite challenge. The study will be conducted at the University of Oxfords Centre for Clinical Vaccinology and Tropical Medicine (CCVTM). The challenge part of the study will take place at the insectary at Imperial College, (Infection and Immunity Section)in London.

Conditions

Malaria

Keywords

Vaccine; Safety; Immunogenicity; Protection; Sporozoite challenge

Outcome Measures

Primary Outcomes (1)

• Safety of new candidate malaria vaccines AdCh63 MSP1 administered alone, and with MVA MSP1 in a prime-boost regime, to healthy volunteers. and safety of the prime-boost vaccine strategy following malaria sporozoite challenge.

  Up to 6 months post enrollment into the study

Secondary Outcomes (1)

• Humoral and cellular immune responses generated by AdCh63 MSP1, when administered to healthy volunteers alone, with MVA MSP1, and following sporozoite challenge. Efficacy of AdCh63 MSP1 and MVA MSP1 against malaria sporozoite challenge

  Up to 6 months post enrollment into the study

Study Arms (2)

Group 1

EXPERIMENTAL

Biological: AdCh63-MSP1 (lower dose) vaccine and MVA-MSP1 vaccine

Group 2

EXPERIMENTAL

Biological: AdCh63-MSP1 vaccine (higher dose) and MVA-MSP1 vaccine followed by challenge

Interventions

AdCh63-MSP1 (lower dose) vaccine and MVA-MSP1 vaccine BIOLOGICAL

Group 1A: single dose of AdCh63-MSP1 vaccine 5 x 10\^9 vp administered IM. Group 1B: single dose of AdCh63-MSP1 vaccine 5 x 10\^9 vp administered IM followed by a single dose of MVA-MSP1 vaccine 5 x 10\^8 vp administered IM 8 weeks later

Group 1

AdCh63-MSP1 vaccine (higher dose) and MVA-MSP1 vaccine followed by challenge BIOLOGICAL

Group 2A: single dose of AdCh63-MSP1 vaccine 5 x 10\^10 vp administered IM. Group 2B: single dose of AdCh63-MSP1 vaccine 5 x 10\^10 vp administered IM followed by a single dose of MVA-MSP1 vaccine 5 x 10\^8 vp administered IM 8 weeks later. Group 2C: single dose of AdCh63-MSP1 vaccine 5 x 10\^10 vp administered IM followed by a single dose of MVA-MSP1 vaccine 5 x 10\^8 vp administered IM 8 weeks later and subsequent sporozoite malaria challenge 12-28 days post second vaccination

Group 2

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 females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day(s) of vaccination and/or challenge
• For males only, willingness to use barrier contraception until 3 months after last vaccination
• Agreement to refrain from blood donation during the course of the study
• Written informed consent

You may not qualify if:

• Significant concern raised by GP in relation to participation
• 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 and/or MVA-vectored 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
• A predicted ten year risk of fatal cardiovascular disease of =\>5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system \[59\]
• History of arrhythmia or congenital QT interval prolongation
• Family history of sudden cardiac death
• Contraindication to both anti-malarial drugs (Riamet and chloroquine)
• o concomitant use with other drugs known to cause QT-interval prolongation, (e.g. macrolides, quinolones, amiodarone etc)
• 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)

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford

Oxford, United Kingdom

Location

MeSH Terms

Conditions

Malaria

Interventions

Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Adrian VS Hill, D.Phil, FRCP

  Univeristy 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: October 27, 2009
• First Posted: October 28, 2009
• Study Start: November 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: March 28, 2011

Record last verified: 2011-03

Locations

GB (1)