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

Phase 3

Completed

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

• Registration Number: NCT00473668
• Lead Sponsor: GlaxoSmithKline

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2007-05-14
• Study First Submitted QC: 2007-05-14
• Study First Posted: 2007-05-15
• Study Start: 2007-06-01
• Primary Completion: 2008-01-30
• Study Completion: 2008-01-30
• Disposition First Submitted: 2009-05-20
• Disposition First Submitted QC: 2009-09-28
• Disposition First Posted: 2009-09-30
• Status Verified: 2017-03
• Results First Submitted: 2017-03-21
• Results First Submitted QC: 2017-08-17
• Last Update Submitted: 2017-08-17
• Results First Posted: 2017-08-18
• Last Update Posted: 2017-08-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 300

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TRITANRIX-HEPB/HIBERIX KFT. GROUP	Zilbrix-Hib	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.
TRITANRIX-HEPB/HIBERIX HD GROUP	Tritanrix™-HepB/ Hiberix™	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.
TRITANRIX-HEPB/HIBERIX LD GROUP	Tritanrix™-HepB/ Hiberix™	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Number of Seroprotected Subjects Against Hepatitis B Surface Antigen (HBs)	At Month 3	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).
Number of Seropositive Subjects Against Polyribosyl-ribitol-phosphate (PRP) Antigens	At Month 3	Seropositivity was defined as antibody concentrations greater than or equal to (≥) 1 microgram/milliliter (µg/mL).
Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Antigen	At Month 3	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).
Number of Subjects With Vaccine Response to Bordetella Pertussis (BPT) Antigen	At Month 3	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.
Number of Seropositive Subjects Against Bordetella Pertussis (BPT) Antigen	At Month 3	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).
Concentration of Antibodies Against Polyribosyl-ribitol-phosphate (PRP) Antigens	At Month 3	Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per milliliter (μg/mL).
Number of Subjects With Any Unsolicited Adverse Events (AEs)	During the 31-day (Day 0-30) follow-up period post-vaccination	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.
Number of Seroprotected Subjects Against Diphteria (D) With Antibody Concentrations Above the Cut-off	At Month 3	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.
Concentration of Antibodies Against Diphtheria (D) and Tetanus (T) Antigens	At Month 3	Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).
Concentration of Antibodies Against Hepatitis B Surface Antigen (HBs)	At Month 3	Concentrations are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL).
Concentration of Antibodies Against Bordetella Pertussis (BPT) Antigen	At Month 3	Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL).
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	During the 4-day (Day 0-3) follow-up period post-vaccination	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.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	During the 4-day (Day 0-3) follow-up period post-vaccination	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.
Number of Subjects With Serious Adverse Events (SAEs)	During the entire study period (Day 0-Month 3)	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.

Trial Locations

Locations (1)

GSK Investigational Site; 🇮🇳 Varanasi, India