Malaria Vaccine Safety and Immunogenicity Study in Healthy Adults

Summary

Targeted malaria elimination (TME), which comprises appropriate case management by village health workers, vector control and mass drug administration, is currently being implemented through pilot projects in selected villages in the Greater Mekong Subregion (GMS) and the scale-up of the intervention to the regional level are underway. Based on mathematical modelling, extending the post-TME parasitaemia-free period in the majority of villagers for as short as 200 days will substantially increase the chances of achieving the interruption of malaria transmission. Immunogenicity of RTS,S is greater in older children, and the short term malaria protective effect is stronger than the overall effect assessed over 1-2 years. Addition of mass RTS,S/AS01E vaccination to the TME arsenal could provide this much needed additional protection.

Currently there are no safety and immunogenicity data for the use of RTS,S/AS01 in Asian populations. This trial will generate the required data for the use of this vaccine in Asian populations. For integration with the current TME activities, which provide mass drug administrations at months M0, M1, and M2, it would be most efficient and practical to provide the vaccine at the same intervals. To address a two round intervention (M0, M2) where a three round intervention is not feasible, one study arm will look at the immune response generated by only two doses of vaccine and antimalarial medications. Recent evidence suggests that a vaccination schedule which includes a fractional dose of RTS,S/AS01 (1/5th of the standard dose) could be similarly or more protective than a schedule with three standard full doses, while requiring less vaccine and resources. The trial therefore includes study arms which will assess the safety and immunogenicity of fractional dose schedules.

Each participant will be randomized into one of the following study arms in a ratio of 20:20:30:30:30:30:30, as follows:

* RTS,S/AS01B Fractional dose group (Group 1)
* Double RTS,S /AS01E Fractional dose group (Group 2)
* RTS,S/AS01E Standard dose group (Group 3)
* RTS,S/AS01E + DHA-PIP+PQ Standard dose group (Group 4)
* RTS,S/AS01E Fractional dose group (Group 5)
* RTS,S/AS01E + DHA-PIP+PQ Fractional dose group (Group 6)
* RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose group (Group 7)

Conditions

• Malaria Vaccine

Interventions

BIOLOGICAL

RTS,S/AS01B Fractional dose

RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.

BIOLOGICAL

Double RTS,S/AS01E Fractional dose

A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.

BIOLOGICAL

RTS,S/AS01E Standard dose

RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.

BIOLOGICAL

RTS,S/AS01E + DHA-PIP+PQ Standard dose

RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2

BIOLOGICAL

RTS,S/AS01E Fractional dose

RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.

BIOLOGICAL

RTS,S/AS01E + DHA-PIP+PQ Fractional dose

RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.

BIOLOGICAL

RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose

RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2

Sponsors & Collaborators

• University of Oxford

  lead OTHER

Principal Investigators

• Lorenz von Seidlein, MD · Mahidol Oxford Tropical Medicine Research Unit

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-06-04

Primary Completion

2018-02-20

Completion

2018-02-20

Countries

• Thailand

Study Locations