An Extended Follow up of a RTS,S/AS01E Malaria Vaccine Trial

Study Overview
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Brief Summary
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Malaria is one of the leading causes of deaths in children below five years old. Despite antimalarial drugs and insecticide treated bed nets, the established means of treatment and protection, malaria still continues to affect many children. A malaria vaccine would be a very effective way of reducing malaria infection in the community. RTS,S/AS01E is a leading malaria vaccine candidate which is being developed for children in Africa. The investigators have done a study to find out if this vaccine is effective in reducing infection by malaria in children aged 5-17 months living in Kenya and Tanzania. The follow up of the original study was 14-18 months. The extended follow up is proposed to continue for another four years.

Detailed Description
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The RTS,S/AS01E candidate malaria vaccine is being developed for the routine immunization of infants and children living in malaria-endemic areas as part of the Expanded Program of Immunization (EPI). 30% efficacy against clinical malaria and 58% efficacy against severe malaria disease was seen with a related vaccine, RTS,S/AS02A, in children aged 1 to 4 years (Malaria-026) in Mozambique. The efficacy against clinical malaria and infection was sustained beyond 18 months. The RTS,S/AS01 vaccines have been developed in parallel with the RTS,S/AS02 vaccines, and differ in the adjuvant formulation which has been shown to be more immunogenic.The utility of a partially effective vaccination depends heavily on the overall effect of malaria incidence during a childs acquisition of natural immunity. However, other cohorts vaccinated in Phase II studies have already discontinued follow up for episodes of malaria, and the planned Phase III studies will run for at most 30 months post vaccination. The proposed extended follow up is expected to run for four years and will inform the design of Phase 4 studies and may prove critical in informing public health policy once the vaccine is licensed.

Official Title
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An Extended Follow up of a Phase 2b Vaccine Trial With RTS,S/AS01E in Kilifi District, Kenya.

Conditions
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Malaria

Intervention / Treatment
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* Biological: RTS,S/AS01E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrollment and vaccination in the RTS,S/AS01E clinical trial (NCT00380393) Written or oral, signed or thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child. Exclusion Criteria: Moving out of the study area, so that follow up is impractical.

Ages Eligible for Study
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Minimum Age: 19 Months
Maximum Age: 35 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| RABIES VACCINE<br>Those subjects who received the active comparator | Biological: RTS,S/AS01E<br>* 0.5MLS of RTS,S/AS01E at 0,1,2 monthly schedule 0.5mls Rabies vaccine at 0,1,2 monthly schedule<br>* Other names: rabies vaccine BP, Sanofi-Pasteur;|
| RTS,S/AS01E<br>The subjects who received investigational product | Biological: RTS,S/AS01E<br>* 0.5MLS of RTS,S/AS01E at 0,1,2 monthly schedule 0.5mls Rabies vaccine at 0,1,2 monthly schedule<br>* Other names: rabies vaccine BP, Sanofi-Pasteur;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long term febrile malaria episodes |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the age distribution of episodes of malaria following vaccination with RTS,S with the age distribution following control vaccination. |  | 4 years | 
| To compare the in vitro markers of naturally acquired immunity in vaccinated and unvaccinated children, and assess the associations of these markers with subsequent episodes of febrile malaria. |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malaria vaccine, RTS,S,