GSK Biologicals is developing in partnership with the PATH Malaria Vaccine Initiative a candidate malaria vaccine 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. The vaccine would also provide protection against infection with hepatitis B virus (HBV).
This trial is being carried out following the demonstration of efficacy of a previous version of the malaria candidate vaccine in children in Mozambique: there, the vaccine demonstrated approximately 30% efficacy against clinical episodes of malaria and approximately 58% efficacy against severe malaria disease.
In order to integrate the malaria vaccine into the EPI regimen, in malaria-endemic regions, for this trial, a 0.5 ml dose of GSK 257049 vaccine has been developed. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Primary Outcome Measures:
- Occurrence of serious adverse events (SAEs) [ Time Frame: From the time of first TETRActHib vaccination until month 6 post Dose 1 ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Occurrence of unsolicited adverse events (AEs) [ Time Frame: after Doses 1, 2 and 3 of TETRActHib over a 14-day follow-up period after Doses 1, 2 and 3 ] [ Designated as safety issue: Yes ]
- Occurrence of unsolicited AEs [ Time Frame: after Doses 1 and 2 of GSK 257049 vaccine or Engerix-B over a 14-day follow-up period after Doses 1 and 2 ] [ Designated as safety issue: Yes ]
- Occurrence of unsolicited AEs [ Time Frame: after Dose 3 of GSK 257049 vaccine or Engerix-B over a 30-day follow-up period (day of vaccination and 29 subsequent days) ] [ Designated as safety issue: Yes ]
- Occurrence of solicited general and local reactions [ Time Frame: over a 7-day follow-up period (day of vaccination and 6 subsequent days) after TETRActHib ] [ Designated as safety issue: Yes ]
- Occurrence of solicited general and local reactions [ Time Frame: over a 7-day follow-up period (day of vaccination and 6 subsequent days) after GSK 257049 vaccine or Engerix-B ] [ Designated as safety issue: Yes ]
- Anti-HBs antibody titers; difference between groups in percent seroprotection [ Time Frame: one month post Dose 3 of GSK 257049 vaccine or Engerix-B ] [ Designated as safety issue: No ]
- Anti-hepatitis B (anti-HBs) antibody titers [ Time Frame: prior to vaccination, 1 month post Dose 3 of or Engerix B ] [ Designated as safety issue: No ]
- Anti-circumsporozoite protein (anti-CS) antibody titers [ Time Frame: prior to vaccination, 1 month post Dose 3, 3½ months post Dose 3 of GSK 257049 vaccine or Engerix B ] [ Designated as safety issue: No ]
- Anti-diphtheria antibody titers [ Time Frame: 1 month post Dose 3 of TETRActHib ] [ Designated as safety issue: No ]
- Anti-tetanus antibody titers [ Time Frame: 1 month post Dose 3 of TETRActHib ] [ Designated as safety issue: No ]
- Anti-pertussis antibody titers [ Time Frame: 1 month post Dose 3 of TETRActHib ] [ Designated as safety issue: No ]
- Anti-polyribosyl ribitol phosphate (anti-PRP) antibody titers [ Time Frame: 1 month post Dose 3 of TETRActHib ] [ Designated as safety issue: No ]
- first P. falciparum malaria infection [ Time Frame: Starting 14 days after last vaccination with extending for 12 weeks. ] [ Designated as safety issue: No ]
- Asexual P. falciparum parasitemia [ Time Frame: At 3½ months post Dose 3 ] [ Designated as safety issue: No ]
Enrollment: |
220 |
Study Start Date: |
August 2005 |
Study Completion Date: |
December 2007 |
Primary Completion Date: |
December 2007 (Final data collection date for primary outcome measure) |
Group B: Active Comparator
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Biological: Engerix B®
IM into the antero-lateral thigh
Biological: TETRActHibTM
IM into the antero-lateral thigh
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Group A: Experimental
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Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049
IM into the antero-lateral thigh
Biological: TETRActHibTM
IM into the antero-lateral thigh
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All infants participating in this phase I/IIb study will receive TETRActHib (a licensed diphtheria-tetanus-pertussis Haemophilus influenzae vaccine manufactured by Aventis Pasteur) by IM injection in their right thigh at 8, 12, and 16 weeks; They will be randomized to receive either the candidate malaria vaccine, GSK 257049 vaccine (0.5 ml dose) or Engerix-B (a licensed hepatitis B vaccine manufactured by GSK Biologicals) by IM injection in their left thigh at 10, 14, 18 weeks. Infants will be followed-up daily for 7 days after each vaccine dose for evaluation of safety and reactogenicity. There will be a 14-day follow-up period after each dose of TETRActHib and after Dose 1 and Dose 2 of GSK 257049 vaccine or Engerix-B, and a one month follow-up period after Dose 3 of GSK 257049 vaccine or Engerix-B for reporting unsolicited symptoms. Serious adverse events will be recorded throughout the 14 month study period. A small amount of blood (2 ml = 1/2 teaspoon) will be obtained at four different time points to measure the immune response elicited by the vaccines administered during this study period. Preliminary indication of vaccine efficacy in this age group will be established by actively monitoring for infection with Plasmodium falciparum.