Charles Darwin University

CDU eSpace
Institutional Repository

 
CDU Staff and Student only
 

Design of a phase III multicenter trial to evaluate the efficacy of the RTS,S/AS01 malaria vaccine in children across diverse transmission settings in Africa

Leach, Amanda J., Vekemans, Johan, Lievens, Marc, Ofori-Anyinam, Opokua, Cahill, Conor, Owusu-Agyei, Seth, Abdulla, Salim, Macete, Eusebio, Njuguna, Patricia, Savarese, Barbara, Loucq, Christian and Ballou, W. Ripley (2011). Design of a phase III multicenter trial to evaluate the efficacy of the RTS,S/AS01 malaria vaccine in children across diverse transmission settings in Africa. Malaria Journal,10:1-12.

Document type: Journal Article
Attached Files (Some files may be inaccessible until you login with your CDU eSpace credentials)
Name Description MIMEType Size Downloads
Download this reading Leach_44329.pdf Published version application/pdf 1.45MB 45
Reading the attached file works best in Firefox, Chrome and IE 9 or later.

IRMA ID 75039815xPUB483
Title Design of a phase III multicenter trial to evaluate the efficacy of the RTS,S/AS01 malaria vaccine in children across diverse transmission settings in Africa
Author Leach, Amanda J.
Vekemans, Johan
Lievens, Marc
Ofori-Anyinam, Opokua
Cahill, Conor
Owusu-Agyei, Seth
Abdulla, Salim
Macete, Eusebio
Njuguna, Patricia
Savarese, Barbara
Loucq, Christian
Ballou, W. Ripley
Journal Name Malaria Journal
Publication Date 2011
Volume Number 10
ISSN 1475-2875   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-79961102845
Start Page 1
End Page 12
Total Pages 12
Place of Publication United Kingdom
Publisher BioMed Central
HERDC Category C1 - Journal Article (DIISR)
Abstract Background
GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative are working in partnership to develop a malaria vaccine to protect infants and children living in malaria endemic regions of sub-Saharan Africa, which can be delivered through the Expanded Programme on Immunization. The RTS,S/AS candidate vaccine has been evaluated in multiple phase I/II studies and shown to have a favourable safety profile and to be well-tolerated in both adults and children. This paper details the design of the phase III multicentre efficacy trial of the RTS,S/AS01 malaria vaccine candidate, which is pivotal for licensure and policy decision-making.

Methods
The phase III trial is a randomized, controlled, multicentre, participant- and observer-blind study on-going in 11 centres associated with different malaria transmission settings in seven countries in sub-Saharan Africa. A minimum of 6,000 children in each of two age categories (6-12 weeks, 5-17 months) have been enrolled. Children were randomized 1:1:1 to one of three study groups: (1) primary vaccination with RTS,S/AS01 and booster dose of RTS,S/AS01; (2) primary vaccination with RTS,S/AS01 and a control vaccine at time of booster; (3) primary vaccination with control vaccine and a control vaccine at time of booster. Primary vaccination comprises three doses at monthly intervals; the booster dose is administered at 18 months post-primary course. Subjects will be followed to study month 32. The co-primary objectives are the evaluation of efficacy over one year post-dose 3 against clinical malaria when primary immunization is delivered at: (1) 6-12 weeks of age, with co-administration of DTPwHepB/Hib antigens and OPV; (2) 5-17 months of age. Secondary objectives include evaluation of vaccine efficacy against severe malaria, anaemia, malaria hospitalization, fatal malaria, all-cause mortality and other serious illnesses including sepsis and pneumonia. Efficacy of the vaccine against clinical malaria under different transmission settings, the evolution of efficacy over time and the potential benefit of a booster will be evaluated. In addition, the effect of RTS,S/AS01 vaccination on growth, and the safety and immunogenicity in HIV-infected and malnourished children will be assessed. Safety of the primary course of immunization and the booster dose will be documented in both age categories.

Conclusions
This pivotal phase III study of the RTS,S/AS01 candidate malaria vaccine in African children was designed and implemented by the Clinical Trials Partnership Committee. The study will provide efficacy and safety data to fulfil regulatory requirements, together with data on a broad range of endpoints that will facilitate the evaluation of the public health impact of the vaccine and will aid policy and implementation decisions.

Trial registration
Clinicaltrials.gov NCT00866619
DOI http://dx.doi.org/10.1186/1475-2875-10-224   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Additional Notes This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Description for Link Link to CC Attribution 2.0 License
URL https://creativecommons.org/licenses/by/2.0/


© copyright

Every reasonable effort has been made to ensure that permission has been obtained for items included in CDU eSpace. If you believe that your rights have been infringed by this repository, please contact digitisation@cdu.edu.au.

 
Versions
Version Filter Type
Access Statistics: 37 Abstract Views, 45 File Downloads  -  Detailed Statistics
Created: Tue, 24 Feb 2015, 12:36:58 CST