Non-inferiority of GSK Biologicals' DTPw-HBV/Hib Compared to Two Formulations of GSK Biologicals' DTPw-HBV/Hib

Non-inferiority of One Formulation of GSK Biologicals' DTPw-HBV/Hib to 2 Formulations of GSK Biologicals' DTPw-HBV/Hib With Respect to the Immune Response to the PRP Antigen, When Administered to Healthy Infants at 6, 10, 14 Weeks of Age

The purpose of this observer-blind study is to generate immunogenicity data with one formulation of GSK Biologicals' DTPw-HBV/Hib vaccine after the primary vaccination course and to demonstrate non-inferiority of this vaccine as compared to two formulations of GSK Biologicals' DTPw-HBV/Hib vaccine with respect to the anti-PRP antibody response. Additionally to assess the reactogenicity and safety of GSK Biologicals' DTPw-HBV/Hib vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Overview

• Status: Completed
• Conditions: Hepatitis B; Tetanus; Diphtheria; Haemophilus Influenzae Type b; Whole Cell Pertussis
• Intervention / Treatment: Biological: Zilbrix-Hib; Biological: Tritanrix™-HepB/ Hiberix™

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Bangalore, India, 560034
    • GSK Investigational Site
  • Kolkotta, India, 700072
    • GSK Investigational Site
  • Varanasi, India, 221005
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
• A male or female between, and including, 6 and 8 weeks of age at the time of the first vaccination.
• Written informed consent obtained from the parent or guardian of the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Born after a gestation period of 36 to 42 weeks inclusive.
• Administration of one dose of hepatitis B vaccine at birth

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period with the exception of OPV.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
• Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting 30 days before the administration of the first vaccine dose, (with the exception of OPV).
• Bacille Calmette-Guérin (BCG) vaccine received after the first 2 weeks of life.
• Hepatitis B vaccine received after the first week of life.
• Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenzae or hepatitis B (except hepatitis B at birth).
• History of diphtheria, tetanus, pertussis, Haemophilus influenzae or hepatitis B diseases.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• A family history of congenital or hereditary immunodeficiency.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
• Major congenital defects or serious chronic illness.
• History of any neurologic disorders or seizures.
• Acute disease at the time of enrolment.
• Other conditions which in the opinion of the investigator may potentially interfere with interpretation of study outcomes.
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TRITANRIX-HEPB/HIBERIX KFT. GROUP; Subjects, male or female, aged 6 to 8 weeks received 3 doses of Tritanrix™-HepB/Hiberix™ Kft. vaccine, administered intramuscularly in the anterolateral thigh at 6, 10 and 14 weeks of age.	Biological: Zilbrix-Hib; Intramuscular injection, 1 dose
Active Comparator: TRITANRIX-HEPB/HIBERIX LD GROUP; Subjects, male or female, aged 6 to 8 weeks received 3 doses of Tritanrix™-HepB/Hiberix™ low-dose (LD) formulation vaccine, administered intramuscularly in the anterolateral thigh at 6, 10 and 14 weeks of age.	Biological: Tritanrix™-HepB/ Hiberix™; Intramuscular injection, 1 dose
Active Comparator: TRITANRIX-HEPB/HIBERIX HD GROUP; Subjects, male or female, aged 6 to 8 weeks received 3 doses of Tritanrix™-HepB/Hiberix™ high-dose (HD) formulation vaccine, administered intramuscularly in the anterolateral thigh at 6, 10 and 14 weeks of age.	Biological: Tritanrix™-HepB/ Hiberix™; Intramuscular injection, 1 dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroprotected Subjects Against Polyribosyl-ribitol-phosphate (PRP) Antigens	A seroprotected subject was defined as a subject with anti-PRP concentrations greater than or equal to (≥) 0.15 microgram per milliliter (µg/mL).	At Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroprotected Subjects Against Hepatitis B Surface Antigen (HBs)	A seroprotected subject is defined as a vaccinated subject with anti-hepatitis B antibody concentration greater than or equal to (≥) 10 milli-international units per milliliter (mIU/mL).	At Month 3
Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Antigen	A seroprotected subject is defined as a vaccinated subject with anti-D and anti-T antibody concentrations greater than or equal to (≥) 0.1 international units per milliliter (IU/mL). Seroprotection was assesed via enzyme-linked immunosorbent assay (ELISA).	At Month 3
Number of Seroprotected Subjects Against Diphteria (D) With Antibody Concentrations Above the Cut-off	Seroprotection cut-off values assessed were greater than or equal to (≥) 0.016 international units per milliliter (IU/mL) in the sera of subjects seronegative before vaccination. Concentrations were assessed via neutralization assay on Vero cells.	At Month 3
Number of Seropositive Subjects Against Polyribosyl-ribitol-phosphate (PRP) Antigens	Seropositivity was defined as antibody concentrations greater than or equal to (≥) 1 microgram/milliliter (µg/mL).	At Month 3
Number of Seropositive Subjects Against Bordetella Pertussis (BPT) Antigen	A seropositive subject was defined as a vaccinated subject with anti-BPT antibody concentration greater than or equal to (≥) 15 ELISA units (EL.U) per milliliter (EL.U/mL).	At Month 3
Number of Subjects With Vaccine Response to Bordetella Pertussis (BPT) Antigen	Vaccine response was defined as: for initially seronegative subjects, antibody concentration greater than or equal to (≥) 15 EL.U/mL; and for initially seropositive subjects, antibody concentration ≥ 1 fold the pre-vaccination antibody concentration.	At Month 3
Concentration of Antibodies Against Polyribosyl-ribitol-phosphate (PRP) Antigens	Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per milliliter (μg/mL).	At Month 3
Concentration of Antibodies Against Diphtheria (D) and Tetanus (T) Antigens	Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).	At Month 3
Concentration of Antibodies Against Hepatitis B Surface Antigen (HBs)	Concentrations are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL).	At Month 3
Concentration of Antibodies Against Bordetella Pertussis (BPT) Antigen	Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL).	At Month 3
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.	During the 4-day (Day 0-3) follow-up period post-vaccination
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were drowsiness, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of any general symptom regardless of intensity grade. Grade 3 Irritability= crying that could not be comforted/prevented normal activity. Grade 3 Drowsiness/Loss of appetite= Drowsiness/Loss of appetite that prevented normal activity. Grade 3 fever = fever above (>) 39.5°C. Related = symptom assessed by the investigator as related to the vaccination.	During the 4-day (Day 0-3) follow-up period post-vaccination
Number of Subjects With Any Unsolicited Adverse Events (AEs)	An unsolicited AE covers 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 and 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.	During the 31-day (Day 0-30) follow-up period post-vaccination
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.	During the entire study period (Day 0-Month 3)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Chatterjee S, Rego SJ, D'Souza F, Bhatia BD, Collard A, Datta SK, Jacquet JM. The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule. BMC Infect Dis. 2010 Oct 15;10:298. doi: 10.1186/1471-2334-10-298.

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: June 1, 2007
• Primary Completion (Actual): January 30, 2008
• Study Completion (Actual): January 30, 2008

Study Registration Dates

• First Submitted: May 14, 2007
• First Submitted That Met QC Criteria: May 14, 2007
• First Posted (Estimate): May 15, 2007

Study Record Updates

• Last Update Posted (Actual): August 18, 2017
• Last Update Submitted That Met QC Criteria: August 17, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Hepatitis B; Pertussis; Diphtheria; Tetanus; Haemophilus influenzae type b Vaccines
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Clostridium Infections; Corynebacterium Infections; Hepatitis B; Whooping Cough; Hepatitis; Tetanus; Diphtheria
• Other Study ID Numbers: 104977

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.

Study Data/Documents

1. Clinical Study Report
   Information identifier: 104977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 104977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 104977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 104977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 104977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 104977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register