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

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00866619

Purpose

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.

Condition	Intervention	Phase
Malaria, Falciparum Malaria	Biological: Malaria Vaccine 257049 Biological: Meningococcal C Conjugate Vaccine Biological: Cell-culture rabies vaccine Biological: TritanrixHepB/Hib Biological: Polio Sabin Oral Polio Vaccine (GSK)	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Efficacy of GSK Biologicals' Candidate Malaria Vaccine (257049) Against Malaria Disease Caused by P. Falciparum Infection in Infants and Children in Africa.

Resource links provided by NLM:

MedlinePlus related topics: Malaria Polio and Post-Polio Syndrome Rabies

Drug Information available for: Rabies Vaccine Malaria Vaccines Rabies Vaccines

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	16000
Study Start Date:	March 2009
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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	Biological: Malaria Vaccine 257049 Vaccine, 0.5mL per dose
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	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
Active Comparator: Group C3C (children) Children enrolled to this group will receive 3 doses of comparator vaccine, and a booster dose of comparator vaccine	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
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	Biological: Malaria Vaccine 257049 Vaccine, 0.5mL per dose 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 R3C (infants) Infants enrolled to this group will receive 3 doses of experimental malaria vaccine, and a booster dose of comparator vaccine	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: 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
Active Comparator: Group C3C (infants) Infants enrolled to this group will receive 3 doses of comparator vaccine, and a booster dose of comparator vaccine	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: 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

Ages Eligible for Study:	6 Weeks to 17 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Burkina Faso
GSK Investigational Site
Ouagadougou, Burkina Faso
Gabon
GSK Investigational Site
Lambaréné, Gabon
Ghana
GSK Investigational Site
Kintampo, Ghana
GSK Investigational Site
Knust- Kumasi, Ghana
Kenya
GSK Investigational Site
Kilifi, Kenya, 80108
GSK Investigational Site
Kisumu, Kenya
Malawi
GSK Investigational Site
Lilongwe, Malawi
Mozambique
GSK Investigational Site
Maputo, Mozambique
Tanzania
GSK Investigational Site
Dar-es-Salaam, Tanzania
GSK Investigational Site
Tanga, Tanzania

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00866619 History of Changes
Other Study ID Numbers:	110021
Study First Received:	March 19, 2009
Last Updated:	February 17, 2011
Health Authority:	Kenya: KEMRI (Kenya Medical Research Institute); Burkina Faso: Comité d'éthique pour la recherche en santé au Burkina Faso (CNERS); Gabon: Ministère de la Santé publique et de l'Hygiène publique; Ghana: Food and Drug Board; Mozambique: Comité Nacional de Bioética para Saùde (CNBS); Tanzania: TFDA (Tanzania Food and Drugs Authority); Malawi: Pharmacy, Medicines and Poisons Board