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

Primary Purpose

Malaria

Status

Completed

Phase

Phase 2

Locations

Malawi

Study Type

Interventional

Intervention

GSK Biological's Investigational Malaria Vaccine 257049

Engerix-B

Tritanrix HepB Hib

BCG

OPV

Rouvax

About this trial

This is an interventional prevention trial for Malaria focused on measuring Africa, malaria vaccine, schedule, EPI, Plasmodium falciparum

Eligibility Criteria

1 Day - 7 Days (Child)All SexesAccepts 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.

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Active Comparator

Arm Label

RTS,S Neo-10-14 Group

RTS,S Neo-10-26 Group

RTS,S 6-10-14 Group

RTS,S 6-10-26 Group

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

RTS,S 10-14-26 Group

RTS,S 14-26-9M Group

Engerix-B Neo Group

Arm 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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Number of Subjects Reported With Serious Adverse Events (SAEs)

An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. "Any" is defined an incidence of a SAE regardless of intensity/severity.

Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)

Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off for the endpoint was a GMC value greater than or equal to (≥) 0.5 EL.U/mL.

Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)

Secondary Outcome Measures

Number of Subjects Reported With Unsolicited Adverse Events (AEs)

An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. "Any" is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. Please note that, for this outcome measure, analysis was performed only on subjects with at least one administered dose of RTS,S/AS01E and/or DTPwHepB/Hib for the Engerix-B Neo Group.

Number of Subjects Reported With Serious Adverse Events (SAEs)

Number of Subjects Reported With Biochemical Abnormalities, for the Alanine Aminotransferase (ALT) Parameter

This outcome measure concerns biochemical abnormalities, for the alanine aminotransferase (ALT) parameter. Subjects' levels were assessed as either normal, Grade 1, Grade 2, Grade 3, Grade 4 or Missing. Normal ALT level was defined as ALT< 60 International units per milliliter (IU/mL). Grade 1 ALT level was defined as 1.1 to 2.5 times the upper limit of normal (ULN). Grade 2 ALT level was defined as 2.6 to 5.0 times the ULN. Grade 3 ALT level was defined as 5.1 to 10.0 times the ULN. Grade 4 ALT level was defined as > 10.0 times the ULN.

Number of Subjects Reported With Biochemical Abnormalities, for the Creatinine (CREA) Parameter

This outcome measure concerns biochemical abnormalities, for the creatinine (CREA) parameter. Subjects' levels were assessed as either normal, Grade 1, Grade 2, Grade 3, Grade 4 or Missing. Normal CREA level was defined as CREA ≤ 106, 88 and 71 micromoles per liter (µmol/L) for subjects 1, 2 or ≥ 2 days of age, respectively. Grade 1 CREA level was defined as 1.1 to 1.3 times the upper limit of normal (ULN). Grade 2 CREA level was defined as 1.4 to 1.8 times the ULN. Grade 3 CREA level was defined as 1.9 to 3.4 times the ULN. Grade 4 CREA level was defined as ≥ 3.5 times the ULN.

Number of Subjects Reported With Haematological Abnormalities, for the Haemoglobin (HAE) Parameter

This outcome measure concerns haematological abnormalities, for the haemoglobin (HAE) parameter. Subjects' levels were assessed as either normal, Grade (G) 1, G 2, G 3, G 4 or Missing. Normal HAE level was defined as HAE > 13.0 and 10.5 grams per deciliter (g/dL) for subjects aged 1 to 21 and 22 to 35 days respectively. Grades were defined as follows: 1) In subjects aged 1 to 21 days: G1 = HAE as 12.0 to 13.0 g/dL, G2 = HAE as 10.0 to 11.9 g/dL, G3 = HAE as 9.0 to 9.9 g/dL, G4 = HAE < 9.0 g/dL; 2) In subjects aged 22 to 35 days: G1 = HAE as 9.5 to 10.5 g/dL, G2 = HAE as 8.0 to 9.4 g/dL, G3 = HAE as 7.0 to 7.9 g/dL, G4 = HAE < 7.0 g/dL; 3) In subjects aged 36 to 56 days: G1 = HAE as 8.5 to 9.4 g/dL, G2 = HAE as 7.0 to 8.4 g/dL, G3 = HAE as 6.0 to 6.9 g/dL, G4 = HAE < 6.0 g/dL; 4) In subjects aged ≥ 57 days: G1 = HAE as 10.0 to 10.9 g/dL, G2 = HAE as 9.0 to 9.9 g/dL, G3 = HAE as 7.0 to 8.9 g/dL, G4 = HAE < 7.0 g/dL.

Number of Subjects Reported With Haematological Abnormalities, for the Platelets (PLA) Parameter

This outcome measure concerns haematological abnormalities, for the platelets (PLA) parameter. Subjects' levels were assessed as either normal, Grade (G) 1, G2, G3, G4 or Missing. Normal PLA level was defined as > 125 x 10 exp 9 PLA per liter (Billions PLA/L). Grade 1 PLA level was defined as 100 to 125 Billions PLA/L. Grade 2 PLA level was defined as 50 to 99 Billions PLA/L. Grade 3 PLA level was defined as 25 to 49 Billions PLA/L. Grade 4 PLA level was defined as < 25 Billions PLA/L.

Number of Subjects Reported With Haematological Abnormalities, for the White Blood Cells (WBC) Parameter

This outcome measure concerns haematological abnormalities, for the white blood cells (WBC) parameter. Subjects' levels were assessed as either normal, Grade 1, Grade 2, Grade 3, Grade 4 or Missing. Normal WBC level was defined as > 2.5 x 10 exp 9 WBC per liter (Billions WBC/L). Grade 1 WBC level was defined as 2.0 to 2.5 Billions WBC/L. Grade 2 WBC level was defined as 1.5 to 1.999 Billions WBC/L. Grade 3 WBC level was defined as 1.0 to 1.499 Billions WBC/L. Grade 4 WBC level was defined as < 1.0 Billions WBC/L.

Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)

Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value for the assay was greater than or equal to (≥) 0.5 EL.U/mL.

Anti-Hepatitis B Surface Antibody (Anti-HBs) Concentrations.

Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The seropositivity and seroprotection cut-off values for the assay were greater than or equal to (≥) 6.2 and 10 mIU/mL, respectively.

Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations

Anti-D and anti-TT antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in International units per milliliter (IU/mL), and tabulated. The seropositivity cut-off value for the assay was ≥ 0.1 IU/mL.

Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations

Anti-PRP antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in microgram per milliliter (µg/mL), and tabulated. The seroprotection cut-off value for the assay was ≥ 0.15 µg/mL.

Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) Antibody Concentrations

Anti-Polio 1, 2 and 3 antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in international units per mililiter (IU/mL) and tabulated. The seroprotection cut-off value for the assay was ≥ 8 IU/mL.

Concentrations of Antibodies Against Acellular B-pertussis (BPT)

Concentrations of anti-BPT antibodies were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value for the assay was ≥ 15 EL.U/mL.

Concentrations of Antibodies Against Measles Antigens

Concentrations of anti measles antibodies were determined by ELISA and expressed as GMCs in milli-international units per millilitre (mIU/mL). The seropositivity cut-off value for the assay was ≥ 150 mIU/mL. Please note that this outcome measure was only assessed in subjects in the RTS,S 14-26-9M and Engerix-B Neo groups.

Number of Subjects Reported With Solicited Local Symptoms

Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.

Number of Subjects Reported With Solicited Local Symptoms

Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.

Number of Subjects Reported With Solicited Local Symptoms

Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.

Number of Subjects Reported With Solicited Local Symptoms

Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.

Number of Subjects Reported With Solicited Local Symptoms

Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity. RTS,S Neo-10-14 Group, RTS,S 6-10-14 Group and Engerix-B Neo Group didn't receive vaccination at this time point.

Number of Subjects Reported With Solicited Local Symptoms

Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.

Number of Subjects Reported With Solicited General Symptoms

Solicited general symptoms assessed include Drowsiness, Fever (temperature by axillary route ≥ 37.5°C), Irritability/Fussiness and Loss of appetite. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity or relationship to vaccination.

Number of Subjects Reported With Solicited General Symptoms

Full Information

NCT ID

NCT01231503

First Posted

October 14, 2010

Last Updated

July 17, 2018

Sponsor

GlaxoSmithKline

Collaborators

The PATH Malaria Vaccine Initiative (MVI)

1. Study Identification

Unique Protocol Identification Number

NCT01231503

Brief Title

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

Official Title

Safety and Immunogenicity of GSK Biologicals' Candidate Malaria Vaccine 257049 When Administered on Different Schedules to Infants in Africa

Study Type

Interventional

2. Study Status

Record Verification Date

June 2018

Overall Recruitment Status

Completed

Study Start Date

January 13, 2011 (Actual)

Primary Completion Date

April 30, 2014 (Actual)

Study Completion Date

December 23, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

Collaborators

The PATH Malaria Vaccine Initiative (MVI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malaria

Keywords

Africa, malaria vaccine, schedule, EPI, Plasmodium falciparum

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

480 (Actual)

8. Arms, Groups, and Interventions

Arm Title

RTS,S Neo-10-14 Group

Arm Type

Experimental

Arm Description

Arm Title

RTS,S Neo-10-26 Group

Arm Type

Experimental

Arm Description

Arm Title

RTS,S 6-10-14 Group

Arm Type

Experimental

Arm Description

Arm Title

RTS,S 6-10-26 Group

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

RTS,S 10-14-26 Group

Arm Type

Experimental

Arm Description

Arm Title

RTS,S 14-26-9M Group

Arm Type

Experimental

Arm Description

Arm Title

Engerix-B Neo Group

Arm Type

Active Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

GSK Biological's Investigational Malaria Vaccine 257049

Other Intervention Name(s)

GSK257049, RTS, S/AS01E

Intervention Description

3 doses, intramuscular (IM) route, in left antero-lateral thigh, as follows: 1) RTS,S Neo-10-14 Group at less than (=<) 7 days, at 10 and 14 weeks (wks) of age; 2) RTS,S Neo-10-26 Group =< 7 days, at 10 and 26 wks of age; 3) RTS,S 6-10-14 Group at 6, 10 and 14 wks of age; 4) RTS,S 6-10-26 Group at 6, 10 and 26 wks of age; 5) Engerix-B Neo/RTS,S 6-10-26 Group at 6, 10 and 26 wks of age; 6) RTS,S 10-14-26 Group at 10, 14 and 26 wks of age; 7) RTS,S 14-26-9M Group at 14 and 26 wks of age and at 9 months of age

Intervention Type

Biological

Intervention Name(s)

Engerix-B

Other Intervention Name(s)

HBV

Intervention Description

1 dose, intramuscular route: left antero-lateral thigh at birth (=< 7 days of age)

Intervention Type

Biological

Intervention Name(s)

Tritanrix HepB Hib

Other Intervention Name(s)

DTPwHepB/Hib

Intervention Description

3 doses, intramuscular route: right antero-lateral thigh at 6, 10 and 14 weeks of age

Intervention Type

Biological

Intervention Name(s)

BCG

Other Intervention Name(s)

Bacille Calmette Guerin tuberculosis vaccine

Intervention Description

1 dose, intradermal route, in shoulder at birth (=< 7 days of age)

Intervention Type

Biological

Intervention Name(s)

OPV

Other Intervention Name(s)

Polio Sabin

Intervention Description

4 doses, orally, at birth (=< 7 days of age) and at 6, 10 and 14 weeks of age

Intervention Type

Biological

Intervention Name(s)

Rouvax

Other Intervention Name(s)

Measles, measles vaccine

Intervention Description

1 dose, intramuscular (IM) route, in left antero-lateral thigh, at 9 months of age

Primary Outcome Measure Information:

Title

Number of Subjects Reported With Serious Adverse Events (SAEs)

Description

Time Frame

From study start at Month 0 up to Month 10.

Title

Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)

Description

Time Frame

At 1 month (M) post Dose 3 of RTS,S/AS01E, e. a. M5 for RTS,S Neo-10-14, RTS,S 6-10-14 and Engerix-B Neo groups

Title

Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)

Description

Time Frame

At 1 month (M) post Dose 3 of RTS,S/AS01E, e. a. M7 for RTS,S Neo-10-26, RTS,S 6-10-26, Engerix-B Neo/RTS,S 6-10-26, and RTS,S 10-14-26 groups

Title

Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)

Description

Time Frame

At 1 month (M) post Dose 3 of RTS,S/AS01E, e. a. M10 for RTS,S 14-26-9M Group

Secondary Outcome Measure Information:

Title

Number of Subjects Reported With Unsolicited Adverse Events (AEs)

Description

Time Frame

During the 30-day (Days 0-29) post vaccination period following 3 doses of RTS,S/AS01E versus DTPwHepB/Hib for the Engerix-B Neo Group

Title

Number of Subjects Reported With Serious Adverse Events (SAEs)

Description

Time Frame

From study start at Month 0 up to Month 18 (corresponding data lock point =23 March 2015)

Title

Number of Subjects Reported With Biochemical Abnormalities, for the Alanine Aminotransferase (ALT) Parameter

Description

Time Frame

At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).

Title

Number of Subjects Reported With Biochemical Abnormalities, for the Creatinine (CREA) Parameter

Description

Time Frame

At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).

Title

Number of Subjects Reported With Haematological Abnormalities, for the Haemoglobin (HAE) Parameter

Description

Time Frame

At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).

Title

Number of Subjects Reported With Haematological Abnormalities, for the Platelets (PLA) Parameter

Description

Time Frame

At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).

Title

Number of Subjects Reported With Haematological Abnormalities, for the White Blood Cells (WBC) Parameter

Description

Time Frame

At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).

Title

Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)

Description

Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value for the assay was greater than or equal to (≥) 0.5 EL.U/mL.

Time Frame

At Screening (SCR), at Month (M) 4, at M5, at M7 and/or at M10, according to the vaccination scheduling for the specific group assessed concerned group

Title

Anti-Hepatitis B Surface Antibody (Anti-HBs) Concentrations.

Description

Time Frame

At Screening (SCR), at Month 5 (M5), at Month 7 (M7) and at Month 10 (M10), according to the vaccination scheduling

Title

Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations

Description

Time Frame

At Month 5

Title

Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations

Description

Time Frame

At Month 5

Title

Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) Antibody Concentrations

Description

Time Frame

At Month 5

Title

Concentrations of Antibodies Against Acellular B-pertussis (BPT)

Description

Time Frame

At Month 5

Title

Concentrations of Antibodies Against Measles Antigens

Description

Time Frame

At Month 10

Title

Number of Subjects Reported With Solicited Local Symptoms

Description

Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.

Time Frame

Within 7 days (Days 0-6) after Week 0 vaccination

Title

Number of Subjects Reported With Solicited Local Symptoms

Description

Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.

Time Frame

Within 7 days (Days 0-6) after Week 6 vaccination

Title

Number of Subjects Reported With Solicited Local Symptoms

Description

Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.

Time Frame

Within 7 days (Days 0-6) after Week 10 vaccination

Title

Number of Subjects Reported With Solicited Local Symptoms

Description

Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.

Time Frame

Within 7 days (Days 0-6) after Week 14 vaccination

Title

Number of Subjects Reported With Solicited Local Symptoms

Description

Time Frame

Within 7 days (Days 0-6) after Week 26 vaccination

Title

Number of Subjects Reported With Solicited Local Symptoms

Description

Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.

Time Frame

Within 7 days (Days 0-6) after Month 9 vaccination

Title

Number of Subjects Reported With Solicited General Symptoms

Description

Time Frame

Within 7 days (Days 0-6) after Week 0 vaccination

Title

Number of Subjects Reported With Solicited General Symptoms

Description

Time Frame

Within 7 days (Days 0-6) after Week 6 vaccination

Title

Number of Subjects Reported With Solicited General Symptoms

Description

Time Frame

Within 7 days (Days 0-6) after Week 10 vaccination

Title

Number of Subjects Reported With Solicited General Symptoms

Description

Time Frame

Within 7 days (Days 0-6) after Week 14 vaccination

Title

Number of Subjects Reported With Solicited General Symptoms

Description

Time Frame

Within 7 days (Days 0-6) after Week 26 vaccination

Title

Number of Subjects Reported With Solicited General Symptoms

Description

Time Frame

Within 7 days (Days 0-6) after Month 9 vaccination

Other Pre-specified Outcome Measures:

Title

Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)

Description

Month 18 immunogenicity data were tertiary objectives, and although not required to be disclosed were included in this result summary at the request of the study team to show the full study immunogenicity results.

Time Frame

At Month 18 post vaccination

Title

Anti-Hepatitis B Surface Antibody (Anti-HBs) Concentrations

Description

Time Frame

At Month 18 post vaccination

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Day

Maximum Age & Unit of Time

7 Days

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Bangwe, Blantyre

ZIP/Postal Code

Country

Malawi

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD is available via the Clinical Study Data Request site (click on the link provided below)

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing URL

https://clinicalstudydatarequest.com

Citations:

PubMed Identifier

29432383

Citation

Witte D, Cunliffe NA, Turner AM, Ngulube E, Ofori-Anyinam O, Vekemans J, Chimpeni P, Lievens M, Wilson TP, Njiram'madzi J, Mendoza YG, Leach A. Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS,S/AS01E Malaria Vaccine Integrated Within an Expanded Program on Immunization Regimen: A Phase II, Single-Center, Open, Controlled Trial in Infants in Malawi. Pediatr Infect Dis J. 2018 May;37(5):483-491. doi: 10.1097/INF.0000000000001937.

Results Reference

derived

Links:

URL

https://clinicalstudydatarequest.com

Description

IPD for this study will be made available via the Clinical Study Data Request site.

Learn more about this trial

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

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