Primary Vaccination Study With a Pneumococcal Conjugate Vaccine in Healthy Children 6 to 10 Weeks of Age

Primary Vaccination Course in Healthy Children Receiving the Pneumococcal Vaccine GSK 1024850A Co-administered With Tritanrix™-HepB/Hib at 6, 10 and 14 Weeks of Age

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 Indian infants with pneumococcal conjugate vaccine GSK1024850A co-administered with a diphtheria, tetanus, whole cell pertussis (DTPw)-combined vaccine during the first 4 months of life. The study will be conducted in India.

Study Overview

• Status: Completed
• Conditions: Streptococcus Pneumoniae; Infections, Streptococcal
• Intervention / Treatment: Biological: Pneumococcal conjugate vaccine GSK1024850A; Biological: Tritanrix-HepB/Hib; Biological: Hiberix; Biological: Tritanrix-HepB

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Kolkata, India, 700073
    • GSK Investigational Site
  • Ludhiana, India, 141 008
    • GSK Investigational Site
  • Pune, India
    • GSK Investigational Site
  • Vellore, India, 632004
    • 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.
• 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).

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 (defined as more than 14 days) 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 (with the exception of hepatitis B immunoglobulins at birth).
• Previous vaccination against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b and/or Streptococcus pneumoniae (with the exception of hepatitis B vaccination at birth or at least 30 days before the subject's first study visit).
• 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.
• Babies for which birth weight is < 2 kilogram.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Synflorix & Tritanrix-HebB/Hib Group; Subjects received SynflorixTM (GSK1024850A) intramuscularly in the right thigh co-administered with TritanrixTM-HepB/Hib intramuscularly in the left thigh at 6-10-14 weeks of age (=study month 0, 1, 2)	Biological: Pneumococcal conjugate vaccine GSK1024850A; Intramuscular injection, 3 doses; Biological: Tritanrix-HepB/Hib; Intramuscular injection, 3 doses; Other Names: DTPw-HBV/Hib
Active Comparator: Hiberix group & Tritanrix-HebB Group; Subjects received HiberixTM intramuscularly in the right thigh co-administered with TritanrixTM-HepB intramuscularly in the left thigh at 6-10-14 weeks of age (=study month 0, 1, 2)	Biological: Hiberix; Intramuscular injection, 3 doses; Other Names: Hib; Biological: Tritanrix-HepB; Intramuscular injection, 3 doses; Other Names: DTPw-HBV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes	Concentrations were expressed as Geometric Mean Concentrations (GMCs) in microgram per milliliter (µg/mL). Pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.	One month after primary immunization (month 3)
Concentration of Antibody Against Protein D (PD)	Concentrations were expressed as GMCs GSK's 22F-inhibition in enzyme-linked-immunosorbent assay (ELISA) units per milliliter (EL.U/mL).	One month after primary immunization (month 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes	Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Cross-reactive pneumococcal serotypes included 6A and 19A. Opsonophagocytic activity was defined as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titer equal to or greater than 8.	One month after primary immunization (month 3)
Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value	Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Cross-reactive pneumococcal serotypes included 6A and 19A. The cut-off was defined as 0.20 microgram per milliliter (µg/mL).	One month after primary immunization
Concentrations of Antibodies Against Pneumococcal Cross-reactive Serotypes	Concentrations were expressed as GMCs in µg/mL. Pneumococcal cross-reactive serotypes included 6A and 19A.	One month after primary immunization (month 3)
Number of Subjects Seropositive for Pneumococcal Serotypes	Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Cross-reactive pneumococcal serotypes included 6A and 19A. Seropositivity was defined as a titer equal to or greater than 0.05 µg/mL	One month after primary immunization (month 3)
Number of Subjects Seropositive for Protein D (PD)	Seropositivity for PD was defined greater than or equal to 100 EL.U/mL.	One month after primary immunization (month 3)
Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP)	Concentration is expressed as GMC in µg/mL.	One month after primary immunization (month 3)
Concentration of Antibodies Against Diphteria (Anti-DT) and Tetanus (Anti-TT)	Concentrations were expressed as GMCs in international units per milliliter (IU/mL).	One month after primary immunization (month 3)
Concentration of Antibody Against Bordetella Pertussis (B. Pertussis)	Concentration was expressed as GMC in EL.U/mL.	One month after primary immunization (month 3)
Concentration of Antibody Against Hepatitis B (Anti-HBs) by Enzyme-Linked ImmunoSorbent Assay (ELISA).	Concentration was expressed as GMC in milli international units per milliliter (mIU/mL). As a decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL), the table shows results following partial or complete retesting/reanalysis.	One month after primary immunization (month 3)
Number of Subjects Seropostive for B. Pertussis	Seropositivity was defined as and antibody concentration equal to or greater than 15 EL.U/mL.	One month after primary immunization (month 3)
Number of Seroprotected Subjects (Anti-DT, Anti-TT, Anti-PRP, Anti-HBs)	Seroprotection was defined as: Anti-DT antibody concentration equal to or greater than 0.1 IU/mL. Anti-TT antibody concentration equal to or greater than 0.1 IU/mL. Anti-PRP antibody concentration equal to or greater than 0.15 µg/mL Anti-HBs antibody concentration greater than or equal to 10 mIU/mL.	One month after primary immunization (month 3)
Number of Seroprotected Subjects (Anti-PRP Above the Cut-off of 1.0 µg/mL)	Anti-PRP antibody concentration equal to or greater than 1.0 µg/mL.	One month after primary immunization (month 3)
Number of Subjects With Solicited Local and General Symptoms	Solicited local symptoms included pain, redness and swelling. Solicited general symptoms included drowsiness, fever (equal to or above 38 degrees Celsius and above 39 degrees Celsius), irritability and loss of appetite.	Within 4 days (day 0-3) after vaccination
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. Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms	Within 31 days (day 0-30) after vaccination
Number of Subjects With Serious Adverse Events (SAEs)	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.	Following first vaccination (Month 0) throughout the entire study period (month 3)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Lalwani S, Chatterjee S, Chhatwal J, Simon A, Ravula S, Francois N, Mehta S, Strezova A, Borys D. Randomized, open-label study of the impact of age on booster responses to the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in children in India. Clin Vaccine Immunol. 2014 Sep;21(9):1292-300. doi: 10.1128/CVI.00068-14. Epub 2014 Jul 9.
• Lalwani S, Chatterjee S, Chhatwal J, Verghese VP, Mehta S, Shafi F, Borys D, Moreira M, Schuerman L. Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal non-typeable Hemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co-administered with the DTPw-HBV/Hib vaccine in Indian infants: a single-blind, randomized, controlled study. Hum Vaccin Immunother. 2012 May;8(5):612-22. doi: 10.4161/hv.19287. Epub 2012 May 1.

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): March 7, 2009
• Primary Completion (Actual): November 13, 2009
• Study Completion (Actual): November 13, 2009

Study Registration Dates

• First Submitted: December 23, 2008
• First Submitted That Met QC Criteria: December 23, 2008
• First Posted (Estimate): December 25, 2008

Study Record Updates

• Last Update Posted (Actual): January 3, 2020
• Last Update Submitted That Met QC Criteria: December 31, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Pneumococcal vaccine; Pneumococcal disease; Primary vaccination
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Pneumococcal Infections; Pneumonia, Pneumococcal; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 111188; 2011-004644-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• 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: 111188
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 111188
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 111188
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 111188
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 111188
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 111188
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: 111188
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register