Pharmacy and Poisons Board
Protocol No: ECCT/18/01/01 Date of Protocol: 06-04-2017
Study Title:
Efficacy, safety and immunogenicity study of GSK Biologicals’ candidate malaria vaccine (SB257049) evaluating schedules with or without fractional doses, early Dose 4 and yearly doses, in children 5-17 months of age.
Study Objectives:
General Objective
  1. The overall objective of the proposed study is to evaluate the safety, immunogenicity and efficacy of the candidate malaria vaccine RTS,S/AS01E in vaccination schedules with or without fractional doses, early Dose 4 and yearly doses, in children 5-17 months of age living in a malaria endemic area of western Kenya.
 
Specific Objectives
  1. To evaluate the efficacy of RTS,S/AS01E primary schedule with or without fractional doses, early dose 4 and yearly doses
  2. To assess efficacy against prevalent P. falciparum infections (defined by a positive blood slide) of each RTS,S/AS01E schedule at cross sectional visits
  3. To describe the antibody response to the anti-circumsporozoite protein of P. falciparum (anti-CS) and hepatitis B surface antigen (anti-HBs) in a subset of subjects for each schedule.
  4. To assess the safety of RTS,S/AS01E for each schedule in terms of serious adverse events (SAEs), unsolicited adverse events (AEs) and AEs of specific interest.
  5. To assess the reactogenicity of RTS,S/AS01E in a subset of subjects terms of solicited local and general AEs.
  6. To assess the safety of RTS,S/AS01E in a subset of subjects in terms of biochemistry (alanine aminotransferase [ALT], creatinine) and hematology (hemoglobin, white blood cells [WBC], platelets) parameters.
  7. To describe the anti-CS antibody response in a subset of subjects in terms of avidity.
Laymans Summary:
What was the main purpose of the study?
Malaria is a sickness that one can get from the bite of a mosquito carrying the malaria parasite. Malaria causes high fever, chills and can lead to serious problems. Problems include low blood levels, loss of consciousness and sometimes death. Young children have the biggest risk for getting very sick and dying from malaria.
Vaccination is a means of protection against a disease. A vaccine increases body’s ability to fight off a particular infection. A malaria vaccine has been developed to protect children against malaria.
The aim of this study was to find out how well the malaria vaccine (RTS,S/AS01E- which will be referred as RTS,S in this document) worked against malaria (vaccine efficacy) when given in different doses and at various schedules. The researchers were also interested in knowing if the vaccine continued to be well tolerated in children at those doses and schedules.
 
When and where did the study take place?
A total of 1500 children from Kenya and Ghana participated in this study (750 Kenya, 750 Ghana)
 
Who took part in the study?
Studies have a list of requirements for participants who can take part or cannot take part in the study.
The children were included in the study if they:
•Were a boy or a girl, aged 5–17 months.
•Had previously received 3 injections of diphtheria, tetanus, pertussis, and hepatitis B vaccine and at least 3 doses of oral polio vaccine.
•Were healthy, without any history of serious illness.
Children were excluded from the study if they:
• Were under the care of an orphanage.
• Were taking long-term medication which could affect their immune responses or unapproved medicines/ vaccines before the study start.
• Had a history of allergy to the vaccine contents or had a history of serious illness that would make the study vaccine unsafe.
Which medicines were studied?
RTS,S-Malaria vaccine
- In this study, a standard vaccine dose (full dose) and smaller amounts called fractional dose (1/5th of the volume)were tested.
Rabies vaccine
- In this study the rabies vaccine was given as a comparator vaccine.
- Comparator is a non-malaria vaccine, helpful to see the malaria vaccine protects against malaria as compared to the comparator.
What happened during the study?
This was an open-label study, which means that the study doctors and the parents of the children knew which vaccine was given.
Children were randomly assigned to a group using a computer program to receive one of the malaria vaccine combinations or the rabies comparator vaccine.
Depending on the group, children received 3, 4, 5 or 6 injections of vaccine at various times. The vaccine injections were given in the arm. The details of the groups and vaccination schedules were as shown in the study design below.
Abstract of Study:

Malaria due to Plasmodium falciparum infection is a major cause of human suffering and an economic drain in many parts of sub-Saharan Africa. The current malaria control programs in endemic areas have relied mainly on three key strategies i.e. use of effective artemisinin-based combination therapies (ACTs), insecticide-treated bednets (ITNs) and indoor residual spraying (IRS). Widescale deployment of these control tools has significantly reduced the burden of malaria in endemic areas. However, challenges such as the emergence of parasite resistance to antimalarial drugs and vector resistance to insecticides used in ITNs and IRS calls for additional and novel tools. Historically, vaccines have proven to be one of the most cost-effective means of preventing infectious diseases and saving lives. Therefore, a malaria vaccine could be an important additional tool that could complement the existing malaria control strategies.

The RTS,S/AS01E is the only vaccine at the most advanced stage of clinical development and the first to be tested in a large phase III clinical trial in children and infants in malaria endemic areas of sub-Saharan Africa. In these phase III studies, the vaccine was shown to be safe, immunogenic and provided moderate protection against malaria. However, vaccine efficacy waned with time and further research is needed to explore alternative vaccination schedules to those tested and other strategies to improve its efficacy. The proposed study will evaluate the efficacy, safety and immunogenicity of RTS,S/AS01E vaccine administered using different schedules from those tested in the phase III trials, with or without fractional doses, early Dose 4 and yearly doses, in children 5-17 months of age in a malaria endemic area of Siaya County, western Kenya. Results from this study will aid in the ongoing evaluation of RTS,S and will be critical in the development of malaria vaccine-based control strategies which, in combination with other interventions, may contribute to the global malaria elimination efforts.