Safety and Immunogenicity of GSK Biologicals' Malaria Vaccine 257049 When Administered on 7 Schedules to African Infants
1 other identifier
interventional
480
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2011
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 14, 2010
CompletedFirst Posted
Study publicly available on registry
November 1, 2010
CompletedStudy Start
First participant enrolled
January 13, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
December 23, 2014
CompletedResults Posted
Study results publicly available
May 20, 2015
CompletedAugust 15, 2018
June 1, 2018
3.3 years
October 14, 2010
May 4, 2015
July 17, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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.
From study start at Month 0 up to Month 10.
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.
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
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.
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
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.
At 1 month (M) post Dose 3 of RTS,S/AS01E, e. a. M10 for RTS,S 14-26-9M Group
Secondary Outcomes (26)
Number of Subjects Reported With Unsolicited Adverse Events (AEs)
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
Number of Subjects Reported With Serious Adverse Events (SAEs)
From study start at Month 0 up to Month 18 (corresponding data lock point =23 March 2015)
Number of Subjects Reported With Biochemical Abnormalities, for the Alanine Aminotransferase (ALT) Parameter
At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
Number of Subjects Reported With Biochemical Abnormalities, for the Creatinine (CREA) Parameter
At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
Number of Subjects Reported With Haematological Abnormalities, for the Haemoglobin (HAE) Parameter
At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
- +21 more secondary outcomes
Other Outcomes (2)
Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)
At Month 18 post vaccination
Anti-Hepatitis B Surface Antibody (Anti-HBs) Concentrations
At Month 18 post vaccination
Study Arms (8)
RTS,S Neo-10-14 Group
EXPERIMENTALSubjects 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.
RTS,S Neo-10-26 Group
EXPERIMENTALSubjects 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.
RTS,S 6-10-14 Group
EXPERIMENTALSubjects 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.
RTS,S 6-10-26 Group
EXPERIMENTALSubjects 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.
Engerix-B Neo/RTS,S 6-10-26 Group
EXPERIMENTALSubjects 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.
RTS,S 10-14-26 Group
EXPERIMENTALSubjects 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.
RTS,S 14-26-9M Group
EXPERIMENTALSubjects 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.
Engerix-B Neo Group
ACTIVE COMPARATORSubjects 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.
Interventions
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
1 dose, intramuscular route: left antero-lateral thigh at birth (=\< 7 days of age)
3 doses, intramuscular route: right antero-lateral thigh at 6, 10 and 14 weeks of age
1 dose, intradermal route, in shoulder at birth (=\< 7 days of age)
4 doses, orally, at birth (=\< 7 days of age) and at 6, 10 and 14 weeks of age
1 dose, intramuscular (IM) route, in left antero-lateral thigh, at 9 months of age
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
- The PATH Malaria Vaccine Initiative (MVI)collaborator
Study Sites (1)
GSK Investigational Site
Bangwe, Blantyre, 3, Malawi
Related Publications (1)
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.
PMID: 29432383DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 14, 2010
First Posted
November 1, 2010
Study Start
January 13, 2011
Primary Completion
April 30, 2014
Study Completion
December 23, 2014
Last Updated
August 15, 2018
Results First Posted
May 20, 2015
Record last verified: 2018-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- IPD is available via the Clinical Study Data Request site (click on the link provided below)
- 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 for this study will be made available via the Clinical Study Data Request site.