Clinical trial NCT00197041: A Study to Evaluate the Safety, Immunogenicity and Efficacy of GlaxoSmithKline (GSK) Biologicals' Candidate Malaria Vaccine RTS,S/AS02A, When Administered to Children Aged 1 to 4 Years Living in a Malaria-endemic Region of Mozambique.
Official title: A Study to Evaluate the Safety, Immunogenicity and Efficacy of GlaxoSmithKline Biologicals' Candidate Malaria Vaccine RTS,S/AS02A, Administered Intramuscularly According to a 0, 1 and 2 Month Vaccination Schedule in Toddlers and Children Aged 1 to 4 Years in a Malaria-endemic Region of Mozambique.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-09-20
Enrollment: 2022
Sex: ALL
Minimum age (years): 1
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Malaria is an important cause of death and serious illness among Mozambican children. Although the risk of malaria can be reduced by drugs and by impregnated bed nets, it would be helpful if children could be protected against malaria by a vaccine.

GSK Biologicals is developing in partnership with Malaria Vaccine Initiative at PATH a candidate malaria vaccine RTS,S/AS02 for the routine immunization of infants and children living in malaria endemic areas. The vaccine would offer protection against malaria disease due to the parasite Plasmodium falciparum and also would provide protection against infection with hepatitis B virus. Previous studies have shown the candidate malaria vaccine RTS,S/AS02 to be safe when administered in adults and children aged 1-11 years. However, to assess if this vaccine could provide protection against malaria in children, this study has been undertaken.

Detailed description: In this study, the participating children will either receive either 3 doses of the new malaria vaccine or the control vaccine which has been selected because of its benefit to the children in preventing important childhood diseases. The control vaccines include the following:

* If the child is of 24 months or older, he/she may receive 3 doses of a vaccine, called Engerix-B™, which protects against hepatitis B.
* If the child is less than 24 months, he/she may receive: two doses of a vaccine called Prevnar® and one dose of a vaccine called Hiberix™. Prevnar® prevents pneumonia and meningitis caused by some Streptococcus pneumoniae bacteria. Hiberix™ prevents severe infections such as pneumonia and meningitis caused by Haemophilus influenzae type b bacteria (Hib). All children will be monitored for the development of malaria disease over an 18-month period extending from the third vaccination. All participants will also be monitored for vaccine safety from first vaccination to study close.

Eligibility criteria: Inclusion Criteria:

* Healthy male and female children, 1 to 4 years of age at the time of first vaccination (up to but not including 5th birthday).
* Written/thumbprinted and witnessed informed consent obtained from the parents or legal guardians.

Exclusion Criteria:

* Major congenital defects or serious chronic illness.
* History of allergic reactions to vaccination or to any component of the Hiberix™, Prevnar® or Engerix-B™ vaccines.
* Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune modifying drugs within six months prior to the first vaccine dose .
* Previous vaccination with an experimental vaccine or with hepatitis B vaccine in children equal to or more than 18 months of age.
* Simultaneous participation in any other clinical trial.
* Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Planned administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of vaccine. An exception, is the receipt of an EPI or licensed vaccine.
* Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.

Primary outcomes:
measure: Time to the first clinical episode of symptomatic Plasmodium falciparum malaria infection detected over the 6-month surveillance period after Dose 3 vaccination.
Secondary outcomes:
measure: Occurrence of episodes of asymptomatic and symptomatic infections of Plasmodium falciparum malaria. Occurrence of solicited symptoms, unsolicited symptoms and SAEs.
Other outcomes:
Locations:
city: Maputo
country: Mozambique
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
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citation: Sacarlal J, Aide P, Aponte JJ, Renom M, Leach A, Mandomando I, Lievens M, Bassat Q, Lafuente S, Macete E, Vekemans J, Guinovart C, Sigauque B, Sillman M, Milman J, Dubois MC, Demoitie MA, Thonnard J, Menendez C, Ballou WR, Cohen J, Alonso PL. Long-term safety and efficacy of the RTS,S/AS02A malaria vaccine in Mozambican children. J Infect Dis. 2009 Aug 1;200(3):329-36. doi: 10.1086/600119.
citation: Guinovart C, Aponte JJ, Sacarlal J, Aide P, Leach A, Bassat Q, Macete E, Dobano C, Lievens M, Loucq C, Ballou WR, Cohen J, Alonso PL. Insights into long-lasting protection induced by RTS,S/AS02A malaria vaccine: further results from a phase IIb trial in Mozambican children. PLoS One. 2009;4(4):e5165. doi: 10.1371/journal.pone.0005165. Epub 2009 Apr 14.
citation: Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Aide P, Sigauque B, Milman J, Mandomando I, Bassat Q, Guinovart C, Espasa M, Corachan S, Lievens M, Navia MM, Dubois MC, Menendez C, Dubovsky F, Cohen J, Thompson R, Ballou WR. Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled trial. Lancet. 2005 Dec 10;366(9502):2012-8. doi: 10.1016/S0140-6736(05)67669-6.