Efficacy of GSK Biologicals' Candidate Malaria Vaccine 257049 Against Malaria Disease in Infants and Children in Africa

• For a primary schedule, the occurrence of cases of malaria meeting the primary case definition for clinical malaria disease. [ Time Frame: Starting 14 days post Dose 3 for 12 months in children aged 6-12 weeks at the time of Dose 1, or until the time at which 450 subjects experience a case, whichever occurs later. ] [ Designated as safety issue: No ]
• For a primary schedule, the occurrence of cases of malaria meeting the primary case definition for clinical malaria disease. [ Time Frame: Starting 14 days post Dose 3 for 12 months in children aged 5-17 months at the time of Dose 1, or until the time at which 450 subjects experience a case, whichever occurs later. ] [ Designated as safety issue: No ]

• Efficacy against severe malaria disease: for a primary schedule (pooled with and without a boost), the occurrence of severe malaria disease meeting the primary and secondary case definitions. [ Time Frame: Timepoint at which 250 subjects are diagnosed with severe malaria meeting the primary case definition or at study end ] [ Designated as safety issue: No ]
• Efficacy against severe malaria disease: for a primary schedule with and without a boost, the occurrence of severe malaria disease meeting the primary and secondary case definitions. [ Time Frame: Starting 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Efficacy against incident severe anemia and malaria hospitalization: for a primary schedule with and without a boost, the occurrence of incident severe anemia and malaria hospitalization meeting the primary and secondary case definitions. [ Time Frame: Starting 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Efficacy; duration of efficacy of a primary course: for a primary schedule without a boost, the occurrence of clinical malaria disease meeting the primary case definition [ Time Frame: Starting 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Efficacy; role of a booster: for a primary schedule with and without a boost, the occurrence of clinical malaria disease meeting the primary case definition. [ Time Frame: Starting at boost until study end ] [ Designated as safety issue: No ]
• Efficacy under different transmission settings: for each site, for a primary schedule with and without a boost, the occurrence of clinical malaria disease meeting the primary case definition. [ Time Frame: Starting 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Efficacy against secondary case definitions of clinical malaria disease: for a primary schedule with and without a boost, the occurrence of clinical malaria disease meeting the secondary case definitions. [ Time Frame: Starting 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Efficacy against prevalence of parasitemia [ Time Frame: For a primary schedule without a boost, at 18 months and 30 months after a primary schedule. For a booster schedule, 12 months after a boost. ] [ Designated as safety issue: No ]
• Efficacy against prevalence of moderate and severe anemia [ Time Frame: For a primary schedule without a boost, at 18 months and 30 months after a primary schedule. For a booster schedule, 12 months after a boost. ] [ Designated as safety issue: No ]
• Safety of a primary course--SAEs (for each age category) [ Time Frame: For a primary schedule, SAEs from Dose 1 until 14 months post Dose 1. For a primary schedule without boost, SAEs starting at Dose 1 until boost, boost until study end and Dose 1 until study end. ] [ Designated as safety issue: No ]
• Safety of a primary course--solicited symptoms (for each age category) [ Time Frame: For a primary schedule, over a 7-day follow-up period after each vaccination (on a subset). ] [ Designated as safety issue: No ]
• Safety of a primary course--unsolicited symptoms related to vaccination or leading to withdrawal (for each age category) [ Time Frame: For a primary schedule, over a 30-day follow-up period after each vaccination. ] [ Designated as safety issue: No ]
• Safety of a booster dose--SAEs (for each age category) [ Time Frame: Starting at, boost until study end. ] [ Designated as safety issue: No ]
• Safety of a booster dose--solicited symptoms (for each age category) [ Time Frame: Over a 7-day follow-up period after the boost (on a subset). ] [ Designated as safety issue: No ]
• Safety of a booster dose--unsolicited symptoms (for each age category) [ Time Frame: Over a 30 day follow-up period after boost ] [ Designated as safety issue: No ]
• Immunogenicity of a primary course: anti-CS antibody titers (for each age category) [ Time Frame: At screening, 1 month post Dose 3, 18 months post Dose 3 and 30 months post Dose 3 (on a subset). ] [ Designated as safety issue: No ]
• Immunogenicity of a primary course: anti-HBs antibody titers (for each age category) [ Time Frame: At screening, 1 month post Dose 3, 18 months post Dose 3 and 30 months post Dose 3 (on a subset). ] [ Designated as safety issue: No ]
• Immunogenicity of a booster dose: anti-CS antibody titers (for each age category) [ Time Frame: At boost, 1 month post boost, 12 months post boost (on a subset). ] [ Designated as safety issue: No ]
• Immunogenicity of a booster dose: anti-HBs antibody titers (for each age category) [ Time Frame: At boost, 1 month post boost, 12 months post boost (on a subset). ] [ Designated as safety issue: No ]
• Immunogenicity of polio serotypes 1, 2 and 3: percentage of subjects with seroprotective levels of anti-polio 1, 2, 3 antibodies (in a subset of African children whose age at first dose will be 6-12 weeks) [ Time Frame: At one month post dose 3 ] [ Designated as safety issue: No ]
• Immunogenicity of polio serotypes 1, 2 and 3: percentage of subjects with seroprotective levels of anti-polio 1, 2, 3 antibodies (in a subset of African children whose age at first dose will be 6-12 weeks) [ Time Frame: At one month post boost ] [ Designated as safety issue: No ]
• Efficacy against other serious illness: the occurrence of other serious illness meeting the primary and secondary case definitions [ Time Frame: 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end. ] [ Designated as safety issue: No ]
• Efficacy against fatal malaria and all-cause mortality: the occurrence of fatal malaria (meeting the case definitions) and all-cause mortality [ Time Frame: 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Effect on growth: to compare the height/length for age z-score [ Time Frame: From study start until study end ] [ Designated as safety issue: No ]
• Effect on growth: to compare the weight for age z-score [ Time Frame: From study start until study end ] [ Designated as safety issue: No ]
• Effect on growth: to compare the mid upper arm circumference for age z-score [ Time Frame: From study start until study end ] [ Designated as safety issue: No ]
• Gender-specific efficacy: in male and female children, for a primary schedule with and without a boost the occurrence of clinical malaria disease meeting the primary case definition [ Time Frame: 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Immunological correlates of protection: in cases and non-cases of malaria disease, CS-antibody titers. [ Time Frame: 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• In HIV-infected children, for each age category, for a primary schedule with and without a boost, the occurrence of SAEs [ Time Frame: At Dose 1 until boost, boost until study end and Dose 1 until study end ] [ Designated as safety issue: No ]
• In HIV-infected children, for each age category, for a primary schedule and a booster dose, the occurrence of unsolicited symptoms related to vaccination or leading to withdrawal [ Time Frame: Over a 30-day follow-up period after each vaccination. ] [ Designated as safety issue: No ]
• In HIV-infected children, for each age category, for a primary schedule with and without a boost, the anti-CS antibody titers [ Time Frame: At screening, 1 month post Dose 3, 18 months post Dose 3 and 30 months post Dose 3 ] [ Designated as safety issue: No ]
• In HIV-infected children for each age category, for a primary schedule with and without a boost, the anti-HBs antibody titers [ Time Frame: At screening, 1 month post Dose 3, 18 months post Dose 3 and 30 months post Dose 3 ] [ Designated as safety issue: No ]
• In low weight for age children (weight for age z-score ≤-2) and in very low weight for age children (weight for age z-score ≤-3), for each age category, for a primary schedule with and without a boost, the occurrence of SAEs [ Time Frame: At Dose 1 until boost, boost until study end and Dose 1 until study end ] [ Designated as safety issue: No ]
• In low weight for age children (weight for age z-score ≤-2) and in very low weight for age children (weight for age z-score ≤-3), for each age category, the occurrence of unsolicited symptoms related to vaccination or leading to withdrawal [ Time Frame: Over a 30-day follow-up period after each vaccination. ] [ Designated as safety issue: No ]
• In low weight for age children (weight for age z-score ≤-2) and in very low weight for age children (weight for age z-score ≤-3), for each age category, for a primary schedule with and without a boost, the anti-CS antibody titers [ Time Frame: At screening, 1 month post Dose 3, 18 months post Dose 3 and 30 months post Dose 3. ] [ Designated as safety issue: No ]
• In low weight for age children (weight for age z-score ≤-2) and in very low weight for age children (weight for age z-score ≤-3), for each age category, for a primary schedule with and without a boost, the anti-HBs antibody titers [ Time Frame: At screening, 1 month post Dose 3, 18 months post Dose 3 and 30 months post Dose 3 ] [ Designated as safety issue: No ]
• In each of at least three study centers, the occurrence of clinical malaria disease meeting the primary and secondary case definitions for clinical malaria [ Time Frame: Over a period starting 14 days post Dose 3 until the last visit of the extension ] [ Designated as safety issue: No ]
• Pooled across at least three study centers, the occurrence of clinical malaria disease meeting the primary and secondary case definitions for clinical malaria [ Time Frame: Over annual time periods ] [ Designated as safety issue: No ]
• Pooled across all participating study centers, the occurrence of severe malaria disease meeting the primary and secondary case definitions for severe malaria [ Time Frame: Over a period starting 14 days post Dose 3 until the last visit of the extension ] [ Designated as safety issue: No ]
• Pooled across all participating study centers, the occurrence of malaria hospitalization meeting the primary and secondary case definitions for malaria hospitalization [ Time Frame: Over a period starting 14 days post Dose 3 until the last visit of the extension ] [ Designated as safety issue: No ]
• Pooled across all participating study centers, the presence of parasitemia [ Time Frame: At annual timepoints during the extension ] [ Designated as safety issue: No ]
• Pooled across all participating study centers, the presence of moderate and severe anemia [ Time Frame: At annual timepoints during the extension ] [ Designated as safety issue: No ]
• Pooled across all participating study centers, the occurrence of all-cause mortality and fatal malaria meeting the primary and secondary case definitions [ Time Frame: Over a period starting 14 days post Dose 3 until the last visit of the extension ] [ Designated as safety issue: No ]
• Pooled across all participating study centers, the occurrence of all-medical hospitalization meeting the primary case definition [ Time Frame: Over a period starting 14 days post Dose 3 until the last visit of the extension ] [ Designated as safety issue: No ]
• Pooled across all participating study centers, the occurrence of pneumonia meeting the primary and secondary case definitions [ Time Frame: Over a period starting 14 days post Dose 3 until the last visit of the extension ] [ Designated as safety issue: No ]
• Pooled across all participating study centers, the occurrence of sepsis meeting the primary case definition [ Time Frame: Over a period starting 14 days post Dose 3 until the last visit of the extension ] [ Designated as safety issue: No ]
• In all participating study centers, the occurrence of SAEs [ Time Frame: From Dose 1 (Day 0) until the end of extension ] [ Designated as safety issue: No ]
• In a subset of subjects, the anti-CS antibody titers [ Time Frame: At annual timepoints during the extension ] [ Designated as safety issue: No ]
• In all subjects at all participating study centers, to compare the height for age z-score [ Time Frame: At the end of extension ] [ Designated as safety issue: No ]

• Efficacy against severe malaria disease: for a primary schedule (pooled with and without a boost), the occurrence of severe malaria disease meeting the primary and secondary case definitions. [ Time Frame: Timepoint at which 250 subjects are diagnosed with severe malaria meeting the primary case definition or at study end ] [ Designated as safety issue: No ]
• Efficacy against severe malaria disease: for a primary schedule with and without a boost, the occurrence of severe malaria disease meeting the primary and secondary case definitions. [ Time Frame: Starting 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Efficacy against incident severe anemia and malaria hospitalization: for a primary schedule with and without a boost, the occurrence of incident severe anemia and malaria hospitalization meeting the primary and secondary case definitions. [ Time Frame: Starting 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Efficacy; duration of efficacy of a primary course: for a primary schedule without a boost, the occurrence of clinical malaria disease meeting the primary case definition [ Time Frame: Starting 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Efficacy; duration of efficacy of a primary course: for a primary schedule without a boost, the occurrence of clinical malaria disease meeting the primary case definition. [ Time Frame: Starting 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end. ] [ Designated as safety issue: No ]
• Efficacy; role of a booster: for a primary schedule with and without a boost, the occurrence of clinical malaria disease meeting the primary case definition. [ Time Frame: Starting at boost until study end ] [ Designated as safety issue: No ]
• Efficacy under different transmission settings: for each site, for a primary schedule with and without a boost, the occurrence of clinical malaria disease meeting the primary case definition. [ Time Frame: Starting 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Efficacy against secondary case definitions of clinical malaria disease: for a primary schedule with and without a boost, the occurrence of clinical malaria disease meeting the secondary case definitions. [ Time Frame: Starting 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Efficacy against prevalence of parasitemia [ Time Frame: For a primary schedule without a boost, at 18 months and 30 months after a primary schedule. For a booster schedule, 12 months after a boost. ] [ Designated as safety issue: No ]
• Efficacy against prevalence of moderate and severe anemia [ Time Frame: For a primary schedule without a boost, at 18 months and 30 months after a primary schedule. For a booster schedule, 12 months after a boost. ] [ Designated as safety issue: No ]
• Safety of a primary course--SAEs (for each age category) [ Time Frame: For a primary schedule, SAEs from Dose 1 until 14 months post Dose 1. For a primary schedule without boost, SAEs starting at Dose 1 until boost, boost until study end and Dose 1 until study end. ] [ Designated as safety issue: No ]
• Safety of a primary course--solicited symptoms (for each age category) [ Time Frame: For a primary schedule, over a 7-day follow-up period after each vaccination (on a subset). ] [ Designated as safety issue: No ]
• Safety of a primary course--unsolicited symptoms related to vaccination or leading to withdrawal (for each age category) [ Time Frame: For a primary schedule, over a 30-day follow-up period after each vaccination. ] [ Designated as safety issue: No ]
• Safety of a booster dose--SAEs (for each age category) [ Time Frame: Starting at, boost until study end. ] [ Designated as safety issue: No ]
• Safety of a booster dose--solicited symptoms (for each age category) [ Time Frame: Over a 7-day follow-up period after the boost (on a subset). ] [ Designated as safety issue: No ]
• Safety of a booster dose--unsolicited symptoms (for each age category) [ Time Frame: Over a 30 day follow-up period after boost ] [ Designated as safety issue: No ]
• Immunogenicity of a primary course: anti-CS antibody titers (for each age category) [ Time Frame: At screening, 1 month post Dose 3, 18 months post Dose 3 and 30 months post Dose 3 (on a subset). ] [ Designated as safety issue: No ]
• Immunogenicity of a primary course: anti-HBs antibody titers (for each age category) [ Time Frame: At screening, 1 month post Dose 3, 18 months post Dose 3 and 30 months post Dose 3 (on a subset). ] [ Designated as safety issue: No ]
• Immunogenicity of a booster dose: anti-CS antibody titers (for each age category) [ Time Frame: At boost, 1 month post boost, 12 months post boost (on a subset). ] [ Designated as safety issue: No ]
• Immunogenicity of a booster dose: anti-HBs antibody titers (for each age category) [ Time Frame: At boost, 1 month post boost, 12 months post boost (on a subset). ] [ Designated as safety issue: No ]
• Immunogenicity of polio serotypes 1, 2 and 3: percentage of subjects with seroprotective levels of anti-polio 1, 2, 3 antibodies (in a subset of African children whose age at first dose will be 6-12 weeks) [ Time Frame: At one month post dose 3 ] [ Designated as safety issue: No ]
• Immunogenicity of polio serotypes 1, 2 and 3: percentage of subjects with seroprotective levels of anti-polio 1, 2, 3 antibodies (in a subset of African children whose age at first dose will be 6-12 weeks) [ Time Frame: At one month post boost ] [ Designated as safety issue: No ]
• Efficacy against other serious illness: the occurrence of other serious illness meeting the primary and secondary case definitions [ Time Frame: 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end. ] [ Designated as safety issue: No ]
• Efficacy against fatal malaria and all-cause mortality: the occurrence of fatal malaria (meeting the case definitions) and all-cause mortality [ Time Frame: 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Effect on growth: to compare the height/length for age z-score [ Time Frame: From study start until study end ] [ Designated as safety issue: No ]
• Effect on growth: to compare the weight for age z-score [ Time Frame: From study start until study end ] [ Designated as safety issue: No ]
• Effect on growth: to compare the mid upper arm circumference for age z-score [ Time Frame: From study start until study end ] [ Designated as safety issue: No ]
• Gender-specific efficacy: in male and female children, for a primary schedule with and without a boost the occurrence of clinical malaria disease meeting the primary case definition [ Time Frame: 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• Immunological correlates of protection: in cases and non-cases of malaria disease, CS-antibody titers. [ Time Frame: 14 days post Dose 3 until boost, boost until study end and 14 days post Dose 3 until study end ] [ Designated as safety issue: No ]
• In HIV-infected children, for each age category, for a primary schedule with and without a boost, the occurrence of SAEs [ Time Frame: At Dose 1 until boost, boost until study end and Dose 1 until study end ] [ Designated as safety issue: No ]
• In HIV-infected children, for each age category, for a primary schedule and a booster dose, the occurrence of unsolicited symptoms related to vaccination or leading to withdrawal [ Time Frame: Over a 30-day follow-up period after each vaccination. ] [ Designated as safety issue: No ]
• In HIV-infected children, for each age category, for a primary schedule with and without a boost, the anti-CS antibody titers [ Time Frame: At screening, 1 month post Dose 3, 18 months post Dose 3 and 30 months post Dose 3 ] [ Designated as safety issue: No ]
• In HIV-infected children for each age category, for a primary schedule with and without a boost, the anti-HBs antibody titers [ Time Frame: At screening, 1 month post Dose 3, 18 months post Dose 3 and 30 months post Dose 3 ] [ Designated as safety issue: No ]
• In low weight for age children (weight for age z-score ≤-2) and in very low weight for age children (weight for age z-score ≤-3), for each age category, for a primary schedule with and without a boost, the occurrence of SAEs [ Time Frame: At Dose 1 until boost, boost until study end and Dose 1 until study end ] [ Designated as safety issue: No ]
• In low weight for age children (weight for age z-score ≤-2) and in very low weight for age children (weight for age z-score ≤-3), for each age category, the occurrence of unsolicited symptoms related to vaccination or leading to withdrawal [ Time Frame: Over a 30-day follow-up period after each vaccination. ] [ Designated as safety issue: No ]
• In low weight for age children (weight for age z-score ≤-2) and in very low weight for age children (weight for age z-score ≤-3), for each age category, for a primary schedule with and without a boost, the anti-CS antibody titers [ Time Frame: At screening, 1 month post Dose 3, 18 months post Dose 3 and 30 months post Dose 3. ] [ Designated as safety issue: No ]
• In low weight for age children (weight for age z-score ≤-2) and in very low weight for age children (weight for age z-score ≤-3), for each age category, for a primary schedule with and without a boost, the anti-HBs antibody titers [ Time Frame: At screening, 1 month post Dose 3, 18 months post Dose 3 and 30 months post Dose 3 ] [ Designated as safety issue: No ]

The purpose of this observer-blind study is to gather key efficacy, safety, and immunogenicity information on GSK's candidate malaria vaccine in infants and children.

The protocol posting document was updated due to a protocol amendment dated 01-Dec-2010. The following sections were amended: outcome measures and inclusion criteria.

This study was double-blind during the first part and single-blind during the extension part.

Including the extension, subjects from 5-17 months will be followed up during 49 months post dose 1 (range: 41-55), while subjects from 6-12 weeks will be followed up during 41 months post dose 1 (range: 35-48).

• Biological: Malaria Vaccine 257049
  Vaccine, 0.5mL per dose
• Biological: Meningococcal C Conjugate Vaccine

  Children enrolled to receive a comparator booster dose (i.e. those enrolled to R3C [children] or C3C [children]) will get 1 dose of Meningococcal C Conjugate Vaccine at the booster dose visit.

  Infants enrolled to receive a comparator booster dose (i.e. those enrolled to R3C [infants] or C3C [infants]) will get 1 dose of Meningococcal C Conjugate Vaccine at the booster dose visit.

  In addition, infants enrolled to receive a primary course comprising 3 doses of comparator vaccine (i.e. those enrolled to C3C [infants]) will get 3 doses of Meningococcal C Conjugate Vaccine.

  Subjects will receive either Meningitec (Wyeth), NeisVac-C (Baxter) or Menjugate (Novartis). Note: where a subject is enrolled to receive 3 doses, each of the 3 doses will be from the same manufacturer

• Biological: Cell-culture rabies vaccine
  Children enrolled to receive a primary course comprising 3 doses of comparator vaccine (i.e. those enrolled to C3C [children]) will get 3 doses of cell-culture rabies vaccine. Subjects will receive either Human Diploid Cell Rabies Vaccine (Sanofi Pasteur) or Purified Chick Embryo Cell Culture Vaccine (i.e. Rabipur, or equivalent) (Novartis). Note: each of the 3 doses will be from the same manufacturer
• Biological: TritanrixHepB/Hib

  Diptheria, Tetanus, whole-cell Pertussis, Hemophilus influenzae (type B) Hepatitis B vaccine (0.5 mL dose).

  All infants enrolled to the trial will receive 3 doses of TritanrixHebB/Hib, a standard EPI-compatible vaccine, commonly administered to infants in sub-Saharan Africa.

• Biological: Polio Sabin Oral Polio Vaccine (GSK)
  All infants enrolled to the trial will receive 3 doses of Polio Sabin Oral Polio Vaccine, a standard EPI-compatible vaccine, commonly administered to infants in sub-Saharan Africa

• Experimental: Group R3R (children)
  Children enrolled to this group will receive 3 doses of experimental malaria vaccine, and a booster dose of experimental malaria vaccine
  Intervention: Biological: Malaria Vaccine 257049
• Active Comparator: Group R3C (children)
  Children enrolled to this group will receive 3 doses of experimental malaria vaccine, and a booster dose of comparator vaccine
  Interventions:

  • Biological: Malaria Vaccine 257049
  • Biological: Meningococcal C Conjugate Vaccine
• Active Comparator: Group C3C (children)
  Children enrolled to this group will receive 3 doses of comparator vaccine, and a booster dose of comparator vaccine
  Interventions:

  • Biological: Meningococcal C Conjugate Vaccine
  • Biological: Cell-culture rabies vaccine
• Experimental: Group R3R (infants)
  Infants enrolled to this group will receive 3 doses of experimental malaria vaccine, and a booster dose of experimental malaria vaccine
  Interventions:

  • Biological: Malaria Vaccine 257049
  • Biological: TritanrixHepB/Hib
  • Biological: Polio Sabin Oral Polio Vaccine (GSK)
• Experimental: Group R3C (infants)
  Infants enrolled to this group will receive 3 doses of experimental malaria vaccine, and a booster dose of comparator vaccine
  Interventions:

  • Biological: Malaria Vaccine 257049
  • Biological: Meningococcal C Conjugate Vaccine
  • Biological: TritanrixHepB/Hib
  • Biological: Polio Sabin Oral Polio Vaccine (GSK)
• Active Comparator: Group C3C (infants)
  Infants enrolled to this group will receive 3 doses of comparator vaccine, and a booster dose of comparator vaccine
  Interventions:

  • Biological: Meningococcal C Conjugate Vaccine
  • Biological: TritanrixHepB/Hib
  • Biological: Polio Sabin Oral Polio Vaccine (GSK)

• Agnandji ST, Lell B, Soulanoudjingar SS, Fernandes JF, Abossolo BP, Conzelmann C, Methogo BG, Doucka Y, Flamen A, Mordmüller B, Issifou S, Kremsner PG, Sacarlal J, Aide P, Lanaspa M, Aponte JJ, Nhamuave A, Quelhas D, Bassat Q, Mandjate S, Macete E, Alonso P, Abdulla S, Salim N, Juma O, Shomari M, Shubis K, Machera F, Hamad AS, Minja R, Mtoro A, Sykes A, Ahmed S, Urassa AM, Ali AM, Mwangoka G, Tanner M, Tinto H, D'Alessandro U, Sorgho H, Valea I, Tahita MC, Kaboré W, Ouédraogo S, Sandrine Y, Guiguemdé RT, Ouédraogo JB, Hamel MJ, Kariuki S, Odero C, Oneko M, Otieno K, Awino N, Omoto J, Williamson J, Muturi-Kioi V, Laserson KF, Slutsker L, Otieno W, Otieno L, Nekoye O, Gondi S, Otieno A, Ogutu B, Wasuna R, Owira V, Jones D, Onyango AA, Njuguna P, Chilengi R, Akoo P, Kerubo C, Gitaka J, Maingi C, Lang T, Olotu A, Tsofa B, Bejon P, Peshu N, Marsh K, Owusu-Agyei S, Asante KP, Osei-Kwakye K, Boahen O, Ayamba S, Kayan K, Owusu-Ofori R, Dosoo D, Asante I, Adjei G, Adjei G, Chandramohan D, Greenwood B, Lusingu J, Gesase S, Malabeja A, Abdul O, Kilavo H, Mahende C, Liheluka E, Lemnge M, Theander T, Drakeley C, Ansong D, Agbenyega T, Adjei S, Boateng HO, Rettig T, Bawa J, Sylverken J, Sambian D, Agyekum A, Owusu L, Martinson F, Hoffman I, Mvalo T, Kamthunzi P, Nkomo R, Msika A, Jumbe A, Chome N, Nyakuipa D, Chintedza J, Ballou WR, Bruls M, Cohen J, Guerra Y, Jongert E, Lapierre D, Leach A, Lievens M, Ofori-Anyinam O, Vekemans J, Carter T, Leboulleux D, Loucq C, Radford A, Savarese B, Schellenberg D, Sillman M, Vansadia P; RTS,S Clinical Trials Partnership. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med. 2011 Nov 17;365(20):1863-75. Epub 2011 Oct 18.
• Swysen C, Vekemans J, Bruls M, Oyakhirome S, Drakeley C, Kremsner P, Greenwood B, Ofori-Anyinam O, Okech B, Villafana T, Carter T, Savarese B, Duse A, Reijman A, Ingram C, Frean J, Ogutu B; Clinical Trials Partnership Committee. Development of standardized laboratory methods and quality processes for a phase III study of the RTS, S/AS01 candidate malaria vaccine. Malar J. 2011 Aug 4;10:223.
• Vekemans J, Marsh K, Greenwood B, Leach A, Kabore W, Soulanoudjingar S, Asante KP, Ansong D, Evans J, Sacarlal J, Bejon P, Kamthunzi P, Salim N, Njuguna P, Hamel MJ, Otieno W, Gesase S, Schellenberg D; Clinical Trials Partnership Committee. Assessment of severe malaria in a multicenter, phase III, RTS, S/AS01 malaria candidate vaccine trial: case definition, standardization of data collection and patient care. Malar J. 2011 Aug 4;10:221.
• Lievens M, Aponte JJ, Williamson J, Mmbando B, Mohamed A, Bejon P, Leach A. Statistical methodology for the evaluation of vaccine efficacy in a phase III multi-centre trial of the RTS, S/AS01 malaria vaccine in African children. Malar J. 2011 Aug 4;10:222.
• Leach A, Vekemans J, Lievens M, Ofori-Anyinam O, Cahill C, Owusu-Agyei S, Abdulla S, Macete E, Njuguna P, Savarese B, Loucq C, Ballou WR; Clinical Trials Partnership Committee. Design of a phase III multicenter trial to evaluate the efficacy of the RTS,S/AS01 malaria vaccine in children across diverse transmission settings in Africa. Malar J. 2011 Aug 4;10:224.

Inclusion Criteria:

All subjects must satisfy the following criteria at study entry:

• A male or female child of:5-17 months (inclusive) of age at time of first vaccination,or between 6-12 weeks of age at time of first vaccination and NOT have already received a dose of vaccine against diphtheria, tetanus or pertussis or Hemophilus influenzae type B and must be > 28 days of age at screening.
• Signed informed consent or thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child.
• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.

All subjects must satisfy the following criteria at the start of the extension phase:

• Subjects who were enrolled and who received at least one vaccine dose in the primary trial phase.
• Subjects who were present for Visit 35 on or before 30 September 2013.
• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits) should be enrolled in the study.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:

• Acute disease at the time of enrolment.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality.
• Anemia associated with clinical signs or symptoms of decompensation or hemoglobin ≥ 5.0 g/dL.
• Major congenital defects.
• History of allergic reactions, significant IgE-mediated events or anaphylaxis to previous immunizations.
• Children with a past history of a neurological disorder or atypical febrile seizure.
• Children with malnutrition requiring hospital admission.
• Children currently meeting the criteria for HIV disease of Stage III or Stage IV severity as defined by the World Health Organization.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to a drug or vaccine that is not licensed for that indication with the exception of studies with the objective of improving the drug treatment or clinical management of severe malaria disease.
• Use of a drug or vaccine that is not approved for that indication other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Previous participation in any other malaria vaccine trial.
• Receipt of a vaccine within the preceding 7 days.
• Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.
• Any other findings that the investigator feels would result in data collected being incomplete or of poor quality