Safety and Immunogenicity of GSK Biologicals' Investigational Malaria Vaccine in HIV Infected Infants and Children

• Occurrence of solicited general and local reactions [ Time Frame: After each vaccine administration over a 7 day follow-up period (day of vaccination and 6 subsequent days) ] [ Designated as safety issue: No ]
• Occurrence of unsolicited symptoms [ Time Frame: After each vaccine administration over a 30 day follow-up period (day of vaccination and 29 subsequent days) ] [ Designated as safety issue: No ]
• Occurrence of non-malaria related SAEs [ Time Frame: From the time of first vaccination until 14 months post Dose 1 ] [ Designated as safety issue: No ]
• Anti-CS antibody titers [ Time Frame: Prior to vaccination and one month post Dose 3 ] [ Designated as safety issue: No ]
• Anti-HBs antibody titers [ Time Frame: Prior to vaccination and one month post Dose 3 ] [ Designated as safety issue: No ]
• Anti-CS antibody titers [ Time Frame: 12 months post Dose 3 ] [ Designated as safety issue: No ]
• Anti-HBs antibody titers [ Time Frame: 12 months post Dose 3 ] [ Designated as safety issue: No ]
• Occurrence of malaria disease according to specific case definitions [ Time Frame: From Day 0 to Day 420 ] [ Designated as safety issue: No ]
• Asexual P. falciparum parasitemia prevalence and density [ Time Frame: 12 months post Dose 3 ] [ Designated as safety issue: No ]
• HIV viral load [ Time Frame: At baseline and at one month, 6 months and 12 months post Dose 3 ] [ Designated as safety issue: No ]
• Rate of positive CD4 and absolute cell counts [ Time Frame: At baseline and at one month, 6 months and 12 months post Dose 3 ] [ Designated as safety issue: No ]
• WHO HIV clinical classification progression [ Time Frame: At baseline, one month, 6 months and 12 months post Dose3 ] [ Designated as safety issue: No ]
• Growth parameters: weight, age/length and middle upper arm circumference for age score [ Time Frame: At Day 0 and Day 420 ] [ Designated as safety issue: No ]

• Occurrence of solicited general and local reactions [ Time Frame: After each vaccine administration over a 7 day follow-up period (day of vaccination and 6 subsequent days) ] [ Designated as safety issue: No ]
• Occurrence of unsolicited symptoms [ Time Frame: After each vaccine administration over a 30 day follow-up period (day of vaccination and 29 subsequent days) ] [ Designated as safety issue: No ]
• Occurrence of non-malaria related SAEs [ Time Frame: From the time of first vaccination until 14 months post Dose 1 ] [ Designated as safety issue: No ]
• Anti-CS antibody titers [ Time Frame: Prior to vaccination and one month post Dose 3 ] [ Designated as safety issue: No ]
• Anti-HBs antibody titers [ Time Frame: Prior to vaccination and one month post Dose 3 ] [ Designated as safety issue: No ]
• Anti-CS antibody titers [ Time Frame: 12 months post Dose 3 ] [ Designated as safety issue: No ]
• Anti-HBs antibody titers [ Time Frame: 12 months post Dose 3 ] [ Designated as safety issue: No ]
• Occurrence of malaria disease according to specific case definitions [ Time Frame: From Day 0 to Day 420 ] [ Designated as safety issue: No ]
• Asexual P. falciparum parasitemia prevalence and density [ Time Frame: 12 months post Dose 3 ] [ Designated as safety issue: No ]
• HIV viral load [ Time Frame: At baseline and at one month, 6 months and 12 months post Dose 3 ] [ Designated as safety issue: No ]
• Rate of positive CD4 and absolute cell counts [ Time Frame: At baseline and at one month, 6 months and 12 months post Dose 3 ] [ Designated as safety issue: No ]
• WHO HIV clinical classification progression [ Time Frame: At baseline, one month, 6 months and 12 months post Dose3 ] [ Designated as safety issue: No ]
• Growth parameters: weight, age/length and middle upper arm circumference for age score [ Time Frame: At Day 0 and 420 ] [ Designated as safety issue: No ]

The purpose of this study is to assess the safety and immunogenicity of the candidate malaria vaccine in HIV-infected infants and children

This protocol posting has been updated due to protocol Amendment 2.

• Biological: GSK Biological's Investigational Malaria Vaccine 257049
  All infants enrolled to group A will receive 3 doses of the experimental vaccine. The vaccine will be administered intramuscularly.
• Biological: Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur);

  To ensure consistent vaccine availability, three cell culture rabies vaccines from two manufacturers may be sourced for this trial (Aventis-Pasteur and Novartis). It will be ensured that an individual child will receive all 3 doses of cell culture rabies vaccine from the same product.

  The vaccine will be administered intramuscularly

• Biological: Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis).

  To ensure consistent vaccine availability, three cell culture rabies vaccines from two manufacturers may be sourced for this trial (Aventis-Pasteur and Novartis). It will be ensured that an individual child will receive all 3 doses of cell culture rabies vaccine from the same product.

  The vaccine will be administered intramuscularly.

• Experimental: Group A
  Infants enrolled to this group will receive 3 doses of the experimental vaccine.
  Intervention: Biological: GSK Biological's Investigational Malaria Vaccine 257049
• Active Comparator: Group B
  Infants enrolled to this group will receive 3 doses of the rabies comparator vaccine.
  Interventions:

  • Biological: Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur);
  • Biological: Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis).

Inclusion Criteria:

All subjects must satisfy ALL the following criteria at study entry:

• A male or female infant or child between and including 6 weeks to 17 months of age, at the time of first vaccination.
• Signed or thumb-printed informed consent obtained from the parent(s)/LAR(s) of the infant or child. Where parents/LARs are illiterate, the consent form will be countersigned by a witness.
• Subjects who the investigator believes that their parents/LARs can and will comply with the requirements of the protocol should be enrolled in the study.
• Subjects who are known to be HIV-infected (documented positive DNA PCR), whether taking HIV antiretroviral treatment (ART) or not.
• Subjects who are born following a normal gestation period.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If ANY exclusion criterion applies, the subject must not be included in the study:

• Acute disease at the time of enrolment. However, the presence of an illness listed as Grade I or Grade II (WHO pediatric AIDS clinical staging) will not of itself constitute an exclusion criterion. Enrolment should be deferred if axillary temperature is >=37.5°C.
• Grade III or Grade IV abnormality on screening laboratory blood sample.
• Grade III or IV AIDS at the time of enrolment (WHO pediatric AIDS clinical staging).
• Major congenital defects.
• Planned administration/administration of a vaccine not foreseen by the study protocol prior to or within 7 days of study vaccine.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine 30 days preceding Dose°1 of study vaccine, or planned use during the study period.
• Previous participation in any other malaria vaccine trial.
• Simultaneous participation in another clinical trial including administration of experimental treatment.
• Same sex twins.
• History of allergic reactions (significant IgE-mediated events) or anaphylaxis to previous immunizations.
• History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine.
• Child in care.