A Study of AdCh63 AMA1 Alone and With MVA AMA1

March 25, 2011 updated by: University of Oxford

A Phase I Study to Assess the Safety and Immunogenicity of New Malaria Vaccine Candidates AdCh63 AMA1 Alone and With MVA AMA1

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, WC1E 6JB
        • Hospital For Tropical Diseases
      • Oxford, United Kingdom, OX3 7LJ
        • Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Old Road, Headington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Simian adenovirus, modified vaccinia Ankara virus expressing malaria antigen AMA1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 6 months following the last vaccination

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Up to 6 moths following the last vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (Actual)

October 1, 2010

Study Completion (Actual)

October 1, 2010

Study Registration Dates

First Submitted

March 25, 2010

First Submitted That Met QC Criteria

March 26, 2010

First Posted (Estimate)

March 29, 2010

Study Record Updates

Last Update Posted (Estimate)

March 28, 2011

Last Update Submitted That Met QC Criteria

March 25, 2011

Last Verified

March 1, 2011

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VAC036

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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