An Extended Follow up of a RTS,S/AS01E Malaria Vaccine Trial (MAL059)

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

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.

Study Overview

• Status: Unknown
• Conditions: Malaria
• Intervention / Treatment: Biological: RTS,S/AS01E

Detailed Description

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 child"s 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.

• Study Type: Observational
• Enrollment (Anticipated): 450

Contacts and Locations

Study Locations

• Kenya
  • Coast Province
    • Kilifi, Coast Province, Kenya, 80108
      • KEMRI Wellcome Trust Research Programme

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The local population is predominantly from Mijikenda ethnic group. The study area is within Kilifi District at the Kenyan coast and majority are subsistence farmers.Kilifi District experiences long rains in May-July and short rains in November/December. Measured Entomological Inoculation Rates in the area vary from 10-50 per year.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Long term febrile malaria episodes	4 years

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: KEMRI-Wellcome Trust Collaborative Research Program
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Ally Olotu, KEMRI-Wellcome Trust Collaborative Research Program

Publications and helpful links

General Publications

• Olotu A, Fegan G, Wambua J, Nyangweso G, Leach A, Lievens M, Kaslow DC, Njuguna P, Marsh K, Bejon P. Seven-Year Efficacy of RTS,S/AS01 Malaria Vaccine among Young African Children. N Engl J Med. 2016 Jun 30;374(26):2519-29. doi: 10.1056/NEJMoa1515257.
• Olotu A, Fegan G, Wambua J, Nyangweso G, Awuondo KO, Leach A, Lievens M, Leboulleux D, Njuguna P, Peshu N, Marsh K, Bejon P. Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure. N Engl J Med. 2013 Mar 21;368(12):1111-20. doi: 10.1056/NEJMoa1207564.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Anticipated): February 1, 2016
• Study Completion (Anticipated): August 1, 2016

Study Registration Dates

• First Submitted: March 31, 2009
• First Submitted That Met QC Criteria: March 31, 2009
• First Posted (Estimate): April 1, 2009

Study Record Updates

• Last Update Posted (Estimate): December 7, 2015
• Last Update Submitted That Met QC Criteria: December 4, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: malaria vaccine; RTS,S,
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: SSC 1512