Safety and Immunogenicity of GSK Biologicals' Malaria Vaccine 257049 When Administered on 7 Schedules to African Infants

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Malaria

Treatments: Biological: Engerix-B; Biological: BCG; Biological: Tritanrix HepB Hib; Biological: Rouvax; Biological: OPV; Biological: GSK Biological's Investigational Malaria Vaccine 257049

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01231503

111315

Details and patient eligibility

About

The aim of the malaria vaccine program of the MVI/GSK partnership is to develop an efficacious malaria vaccine that is deliverable through the existing system, the Expanded Program on Immunization (EPI) of WHO. This study has been designed to:

• Investigate the safety and immunogenicity of 7 infant immunization schedules of the experimental malaria vaccine integrated with an EPI regimen.
• Investigate how to maximize the antibody response to the experimental malaria vaccine.

Enrollment: 480 patients

Sex: All

Ages: 1 to 7 days old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

All subjects must satisfy the following criteria at study entry:

• A male or female infant between 1 and 7 days (inclusive) of age (where day 1 is day of birth).
• Signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child. Where parent(s)/guardian(s) are illiterate, the consent form will be countersigned by a witness.
• 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.
• Born to a mother negative for HIV antibody and Hepatitis B surface antigen.
• Subjects who are born after a normal gestation period (between 37 and 42 weeks) (Gestational age will be determined by carrying out a clinical assessment on infants according to the principles set out by Dubowitz (1970) in the first 5 days of life).
• A minimum weight of 2.5 kg.

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 or chronic illness determined by clinical or physical examination and laboratory screening tests including, but not limited to:

  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • A family history of congenital or hereditary immunodeficiency.
  • Major congenital defects.
  • History of any neurological disorders or seizures.

• Laboratory screening tests out of normal ranges/limits defined per protocol.

• Previous vaccination with diphtheria, tetanus, pertussis (whole-cell or acellular), Hemophilus influenzae type b, hepatitis B, BCG tuberculosis, measles or oral polio vaccines.

• Planned administration/administration of a licensed vaccine (i.e. a vaccine that is approved by one of the following authorities: FDA or EU member state or WHO [with respect to prequalification]) not foreseen by the study protocol within 7 days of the first dose of study vaccine.

• Administration of immunoglobulins, blood transfusions or other blood products since birth to the first dose of study vaccine or planned administration during the study period.

• Use of a drug or vaccine that is not approved for that indication (by one of the following authorities: FDA or EU member state or WHO [with respect to prequalification]) other than the study vaccine starting at birth or planned use during the study period.

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.

• Simultaneous participation in any other clinical trial.

• Same-sex twins (to avoid misidentification).

• Maternal death.

• 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 vaccine.

• Children will not be enrolled if any maternal, obstetrical or neonatal event that has occurred might, in the judgment of the investigator, result in increased neonatal/infant morbidity

• Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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480 participants in 8 patient groups

RTS,S Neo-10-14 Group

Experimental group

Description:

Subjects received 3 doses of RTS,S/AS01E (GSK257049) when ≤ 7 days of age and at 10 and 14 weeks of age. In addition, all subjects received a 3-doses course of Tritanrix HepB/Hib (DTPwHepB/Hib), administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine (BCG), administered when ≤ 7 days of age, 4 doses of Polio Sabin (OPV), administered when ≤7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax (Measles), administered at 9 months of age. The RTS,S/AS01E vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The DTPwHepB/Hib and Measles vaccines were administered IM in the right antero-lateral thigh and the OPV vaccine orally. The BCG vaccine was administered via intradermal route in the shoulder.

Treatment:

Biological: BCG

Biological: Rouvax

Biological: OPV

Biological: GSK Biological's Investigational Malaria Vaccine 257049

Biological: Tritanrix HepB Hib

RTS,S Neo-10-26 Group

Experimental group

Description:

Subjects received 3 doses of RTS,S/AS01E (GSK257049) when ≤ 7 days of age and at 10 and 26 weeks of age. In addition, all subjects received a 3-doses course of Tritanri xHepB/Hib (DTPwHepB/Hib), administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine (BCG), administered when ≤ 7 days of age, 4 doses of Polio Sabin (OPV), administered when below ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax (Measles), administered at 9 months of age. The RTS,S/AS01E vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The DTPwHepB/Hib and Measles vaccines were administered IM in the right antero-lateral thigh and the OPV vaccine orally. The BCG vaccine was administered via intradermal route in the shoulder.

Treatment:

Biological: BCG

Biological: Rouvax

Biological: OPV

Biological: GSK Biological's Investigational Malaria Vaccine 257049

Biological: Tritanrix HepB Hib

RTS,S 6-10-14 Group

Experimental group

Description:

Subjects received 3 doses of RTS,S/AS01E (GSK257049) at 6, 10 and 14 weeks of age In addition, all subjects received a 3-doses course of Tritanrix HepB/Hib (DTPwHepB/Hib), administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine (BCG), administered when ≤ 7 days of age, 4 doses of Polio Sabin (OPV), administered when ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax (Measles), administered at 9 months of age. The RTS,S/AS01E vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The DTPwHepB/Hib and Measles vaccines were administered IM in the right antero-lateral thigh and the OPV vaccine orally. The BCG vaccine was administered via intradermal route in the shoulder.

Treatment:

Biological: BCG

Biological: Rouvax

Biological: OPV

Biological: GSK Biological's Investigational Malaria Vaccine 257049

Biological: Tritanrix HepB Hib

RTS,S 6-10-26 Group

Experimental group

Description:

Subjects received 3 doses of RTS,S/AS01E (GSK257049) at 6, 10 and 26 weeks of age. In addition, all subjects received a 3-doses course of Tritanrix HepB/Hib (DTPwHepB/Hib), administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine (BCG), administered when ≤ 7 days of age, 4 doses of Polio Sabin (OPV), administered when ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax (Measles), administered at 9 months of age. The RTS,S/AS01E vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The DTPwHepB/Hib and Measles vaccines were administered IM in the right antero-lateral thigh and the OPV vaccine orally. The BCG vaccine was administered via intradermal route in the shoulder.

Treatment:

Biological: BCG

Biological: Rouvax

Biological: OPV

Biological: GSK Biological's Investigational Malaria Vaccine 257049

Biological: Tritanrix HepB Hib

Engerix-B Neo/RTS,S 6-10-26 Group

Experimental group

Description:

Subjects received one dose of Engerix-B (HBV) when ≤ 7 days of age followed by 3 doses of RTS,S/AS01E (GSK257049) at 6, 10 and 26 weeks of age In addition, all subjects received a 3-doses course of Tritanrix HepB/Hib (DTPwHepB/Hib), administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine (BCG), administered when ≤ 7 days of age, 4 doses of Polio Sabin (OPV), administered when ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax (Measles), administered at 9 months of age. The RTS,S/AS01E and HBV vaccines were administered intramuscularly (IM) in the left antero-lateral thigh. The DTPwHepB/Hib and Measles vaccines were administered IM in the right antero-lateral thigh and the OPV vaccine orally. The BCG vaccine was administered via intradermal route in the shoulder.

Treatment:

Biological: BCG

Biological: Engerix-B

Biological: Rouvax

Biological: OPV

Biological: GSK Biological's Investigational Malaria Vaccine 257049

Biological: Tritanrix HepB Hib

RTS,S 10-14-26 Group

Experimental group

Description:

Subjects received 3 doses of RTS,S/AS01E (GSK257049) at 10, 14 and 26 weeks of age. In addition, all subjects received a 3-doses course of Tritanrix HepB/Hib (DTPwHepB/Hib), administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine (BCG), administered when ≤ 7 days of age, 4 doses of Polio Sabin (OPV), administered when below ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax (Measles), administered at 9 months of age. The RTS,S/AS01E vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The DTPwHepB/Hib and Measles vaccines were administered IM in the right antero-lateral thigh and the OPV vaccine orally. The BCG vaccine was administered via intradermal route in the shoulder.

Treatment:

Biological: BCG

Biological: Rouvax

Biological: OPV

Biological: GSK Biological's Investigational Malaria Vaccine 257049

Biological: Tritanrix HepB Hib

RTS,S 14-26-9M Group

Experimental group

Description:

Subjects received 3 doses of RTS,S/AS01E (or GSK257049) at 14 and 26 weeks of age and at 9 months of age. In addition, all subjects received a 3-doses course of Tritanrix HepB/Hib (DTPwHepB/Hib), administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine (BCG), administered when below ≤ 7 days of age, 4 doses of Polio Sabin (OPV), administered when below ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax (Measles), administered at 9 months of age. The RTS,S/AS01E vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The DTPwHepB/Hib and Measles vaccines were administered IM in the right antero-lateral thigh and the OPV vaccine orally. The BCG vaccine was administered via intradermal route in the shoulder.

Treatment:

Biological: BCG

Biological: Rouvax

Biological: OPV

Biological: GSK Biological's Investigational Malaria Vaccine 257049

Biological: Tritanrix HepB Hib

Engerix-B Neo Group

Active Comparator group

Description:

Subjects in this group received one dose of Engerix-B (HBV) ≤ 7 days of age. In addition, all subjects received a 3-doses course of Tritanrix HepB/Hib (DTPwHepB/Hib), administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine (BCG), administered when below ≤ 7 days of age, 4 doses of Polio Sabin (OPV), administered when ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax (Measles), administered at 9 months of age. The HBV vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The DTPwHepB/Hib and Measles vaccines were administered IM in the right antero-lateral thigh and the OPV vaccine orally. The BCG vaccine was administered via intradermal route in the shoulder.

Treatment:

Biological: BCG

Biological: Engerix-B

Biological: Rouvax

Biological: OPV

Biological: Tritanrix HepB Hib