Primary Vaccination Course in Children Receiving the Pneumococcal Vaccine GSK 1024850A, Zilbrix™ Hib and Polio Sabin™

Primary Vaccination Course in Children Receiving the Pneumococcal Vaccine GSK 1024850A Co-administered With Zilbrix™ Hib and Polio Sabin™

The purpose of this study is to assess the immunogenicity in terms of antibody response and the safety/reactogenicity in terms of solicited and unsolicited symptoms and serious adverse events following primary vaccination of African Sub-Saharan infants with pneumococcal conjugate vaccine GSK 1024850A co-administered with a diphtheria, tetanus, whole cell pertussis (DTPw)-combined vaccine and oral polio vaccine in children during the first 4 months of life.

Study Overview

• Status: Completed
• Conditions: Infections, Streptococcal
• Intervention / Treatment: Biological: GSK Biologicals' Synflorix™; Biological: GSK Biologicals' Polio Sabin™; Biological: GSK Biologicals' Zilbrix™ Hib

Detailed Description

Vaccination course at 6, 10, 14 weeks of age.

• Study Type: Interventional
• Enrollment (Actual): 365
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mali
  • Bamako, Mali
    • GSK Investigational Site
• Nigeria
  • Ikeja / Lagos, Nigeria, P.M.B. 21266
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects between, and including 6-10 weeks of age at the time of the first vaccination.
• Subjects for whom the investigator believes that their parent(s)/guardian(s) can and will comply with the requirements of the protocol should be enrolled in the study.
• Written or oral, signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child/ward. Where parent(s)/guardian(s) are illiterate, the consent form will be countersigned by a witness.
• Free of any known or suspected health problems (as established by medical history and clinical examination before entering into the study), that would contraindicate the initiation of routine immunizations outside a clinical trial context.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of the study vaccines, or planned use during the study period.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
• Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
• A family history of congenital or hereditary immunodeficiency.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period (Hepatitis B immunoglobulins at birth are allowed).
• Previous vaccination against, diphtheria, tetanus, pertussis, Haemophilus influenzae type b and/or Streptococcus pneumoniae.
• History of, or intercurrent diphtheria, tetanus, pertussis, hepatitis B, Streptococcus and Haemophilus influenzae type b disease.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
• History of any neurological disorders or seizures.
• Major congenital defects or serious chronic illness.
• Acute disease at the time of enrolment. Study entry should be delayed until the illness has improved.
• Babies for which birth weight is < 2 kilogram (if known) at Visit 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SYNFLORIX™ + ZILBRIX™ HIB + POLIO SABIN™; Subjects in this group received 3 doses of Synflorix™ vaccine, according to a 3-dose schedule at 6-10-14 weeks of age co-administered with 3 doses of Expanded Program on Immunization (EPI) vaccines Zilbrix™ Hib and Polio Sabin™ according to the same schedule. The Synflorix™ and Zilbrix™ Hib vaccines were administered by intramuscular injection, in the right and left thigh respectively. The Polio Sabin™ vaccine was administered orally.	Biological: GSK Biologicals' Synflorix™; 3 IM doses.; Other Names: 10Pn; Biological: GSK Biologicals' Polio Sabin™; 3 oral doses; Other Names: OPV; Biological: GSK Biologicals' Zilbrix™ Hib; 3 IM doses.; Other Names: DTPw-HBV/Hib vaccine
EXPERIMENTAL: ZILBRIX™ HIB + POLIO SABIN™; Subjects in this group received 3 doses of Expanded Program on Immunization (EPI) vaccines Zilbrix™ Hib and Polio Sabin™ according to a 3-dose schedule at 6-10-14 weeks of age. The Zilbrix™ Hib vaccine was administered by intramuscular injection, in the left thigh. The Polio Sabin™ vaccine was administered orally.	Biological: GSK Biologicals' Polio Sabin™; 3 oral doses; Other Names: OPV; Biological: GSK Biologicals' Zilbrix™ Hib; 3 IM doses.; Other Names: DTPw-HBV/Hib vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes	Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity cut-off for the assay was an anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) concentrations greater than or equal to (≥) 0.05 microgram per milliliter (μg/mL).	At Month 3, one month after the administration of the third dose of Synflorix vaccine
Antibody Concentrations Against Protein D (Anti-PD Antibodies)	Anti-PD antibody concentrations were expressed in enzyme-linked immunsorbent assay (ELISA) units per milliliter (EL.U/mL). Seropositivity cut-off for the assay was an anti-PD antibody concentrations ≥ 100 EL.U/mL.	At Month 3, one month after the administration of the third dose of Synflorix vaccine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A)	Seropositivity status was defined as anti-pneumococcal cross-reactive serotypes 6A/19A antibody concentrations (Anti-6A/19A) ≥ 0.05 microgram per milliliter (μg/mL).	At Month 3, one month after the administration of the third dose of Synflorix vaccine
Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes	Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity status was defined as an opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 8.	At Month 3, one month after the administration of the third dose of Synflorix vaccine
Titers for Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes	Pneumococcal serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19A. Seropositivity status was defined as an opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A (OPA-6A and 19A) ≥ 8.	At Month 3, one month after the administration of the third dose of Synflorix vaccine
Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes	Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity cut-off for the assay was an anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) concentrations ≥ 0.05 microgram per milliliter (μg/mL).	At Month 3, one month after the administration of the third dose of Synflorix vaccine
Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes	Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seroprotection cut-off for the assay was an anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) concentrations ≥ 0.2 microgram per milliliter (μg/mL).	At Month 3, one month after the administration of the third dose of Synflorix vaccine
Number of Subjects Seropositive for Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A)	Serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19A. Seropositivity status was defined as anti-pneumococcal cross-reactive serotypes 6A/19A antibody concentrations (Anti-6A/19A) ≥ 0.05 microgram per milliliter (μg/mL).	At Month 3, one month after the administration of the third dose of Synflorix vaccine
Number of Subjects Seroprotected Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A)	Serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19 A. Seroprotection cut-off for the assay was an anti-6A/19A antibody concentrations ≥ 0.2 microgram per milliliter (μg/mL).	At Month 3, one month after the administration of the third dose of Synflorix vaccine
Number of Subjects Seropositive for Antibodies Against Protein D (Anti-PD Antibodies)	Seropositivity cut-off for the assay was an anti-PD antibody concentrations ≥ 100 EL.U/mL.	At Month 3, one month after the administration of the third dose of Synflorix vaccine
Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes	Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity status was defined as an opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 8.	At Month 3, one month after the administration of the third dose of Synflorix vaccine
Number of Subjects Seropositive for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes	Pneumococcal serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19A. Seropositivity status was defined as an opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A (OPA-6A and 19A) ≥ 8.	At Month 3, one month after the administration of the third dose of Synflorix vaccine
Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations	Anti-BPT antibody concentrations were expressed in enzyme-linked immunosorbent assay (ELISA) unit per millilitre (EL.U/mL). Seropositivity cut-off for the assay was defined as an anti-BPT antibody concentrations ≥ 15 EL.U/mL	At Month 3, one month after the administration of the third dose of Synflorix vaccine
Number of Subjects Seropositive for Antibodies Against Bordetella Pertussis (Anti-BPT)	Seropositivity cut-off for the assay was defined as an anti-BPT antibody concentration ≥ 15 enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL).	At Month 3, one month after the administration of the third dose of DTPw-HBV/Hib vaccine
Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations	The seroprotection cut-off for the assay was an anti-diphtheria toxoid or anti-tetanus toxoid antibody concentrations ≥ 0.1 international unit per milliliter (IU/mL).	At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine
Number of Subjects Seroprotected Against Diphtheria (D) and Tetanus Toxoids (TT) Antigens	A subject seroprotected against D/TT antigens was defined as a subject with an Anti-D/-TT antibody concentration ≥ 0.1 IU/mL.	At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine
Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations	Anti-PRP antibody concentrations were measured and tabulated in microgram per milliliter (μg/mL). Cut-off for the assay was ≥ 0.15 μg/mL.	At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine
Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP)	Anti-PRP antibody concentrations were expressed in microgram per milliliter (μg/mL). The seroprotection cut-off applied for the assay was ≥ 0.15 μg/mL.	At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine
Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP) Antigens	Anti-PRP antibody concentrations were expressed in microgram per milliliter (μg/mL). The seroprotection cut-off applied for the assay was ≥ 1 μg/mL.	At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine
Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations	The seroprotection cut-off for the endpoint was an anti-HBs antibody concentration ≥ 10 milli-international units per milliliter (mIU/mL).	At Month 3, one month after the administration of the third dose of Tritanrix -HepB /Hiberix vaccine
Number of Subjects Seroprotected Against Anti-Hepatitis B Surface Antigens (HBs).	The seroprotection cut-off values considered for this endpoint were an anti-HBs antibody concentration ≥ 10 and 100 milli-international units per milliliter (mIU/mL).	At Month 3, one month after the administration of the third dose of Tritanrix HepB/ Hiberix vaccine
Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms	Solicited local symptoms assessed included pain, redness and swelling. Grade 3 pain was defined as crying when limb was moved/ spontaneously painful. Grade 3 swelling/ redness was defined as swelling/ redness greater than (>) 30 millimeters (mm). "Any" was defined as incidence of the specified symptom regardless of intensity.	Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines
Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms	Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature ≥ 38.0°C), irritability, and loss of appetite. "Any" was defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. Grade 3 drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (rectal temperature) greater than (>) 40.0 degree Celsius (°C). Grade 3 irritability was defined as crying that could not be comforted/ preventing normal activity. Grade 3 loss of appetite was defined as the subject not eating at all.	Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines
Number of Subjects With Fever (Temperature Measured Rectally) > the Cut-off	The cut-off for the assay was > 39.0°C.	Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines
Number of Subjects 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" was defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination.	Within the 31-day (Days 0-30) follow-up periods post vaccination, across doses and across vaccines
Number of Subjects With Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity.	Throughout the entire study period, from Month 0 to Month 3

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Dicko A, Odusanya OO, Diallo AI, Santara G, Barry A, Dolo A, Diallo A, Kuyinu YA, Kehinde OA, Francois N, Borys D, Yarzabal JP, Moreira M, Schuerman L. Primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in infants in Mali and Nigeria: a randomized controlled trial. BMC Public Health. 2011 Nov 23;11:882. doi: 10.1186/1471-2458-11-882.
• Odusanya OO, Kuyinu YA, Kehinde OA, Francois N, Yarzabal JP, Moreira M, Borys D, Schuerman L. Immunogenicity, safety and reactogenicity of the 10-valent pneumococcal non-typeable haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Nigerian Infants: a randomised trial. Niger Postgrad Med J. 2013 Dec;20(4):272-81.
• Silfverdal SA, Coremans V, Francois N, Borys D, Cleerbout J. Safety profile of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Expert Rev Vaccines. 2017 Feb;16(2):109-121. doi: 10.1586/14760584.2016.1164044. Epub 2016 Sep 30.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 18, 2008
• Primary Completion (ACTUAL): November 9, 2009
• Study Completion (ACTUAL): December 10, 2009

Study Registration Dates

• First Submitted: May 13, 2008
• First Submitted That Met QC Criteria: May 14, 2008
• First Posted (ESTIMATE): May 15, 2008

Study Record Updates

• Last Update Posted (ACTUAL): November 15, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Streptococcus pneumoniae; pneumococcal conjugate vaccine
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 110521; 2011-004650-25 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this 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 Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Study Protocol
   Information identifier: 110521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 110521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 110521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 110521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Annotated Case Report Form
   Information identifier: 110521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 110521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: 110521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register