Back to resultsNon-inferiority of GSK Biologicals' DTPw-HBV/Hib Compared to Two Formulations of GSK Biologicals' DTPw-HBV/Hib
Primary Purpose
Whole Cell Pertussis, Haemophilus Influenzae Type b, Tetanus
Status
Completed
Phase
Phase 3
Locations
India
Study Type
Interventional
Intervention
Zilbrix-Hib
Tritanrix™-HepB/ Hiberix™
Sponsored by
About this trial
This is an interventional prevention trial for Whole Cell Pertussis focused on measuring Hepatitis B, Tetanus, Diphtheria, Pertussis, Haemophilus influenzae type b Vaccines
Eligibility Criteria
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.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
TRITANRIX-HEPB/HIBERIX KFT. GROUP
TRITANRIX-HEPB/HIBERIX LD GROUP
TRITANRIX-HEPB/HIBERIX HD GROUP
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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).
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).
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.
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).
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).
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.
Concentration of Antibodies Against Polyribosyl-ribitol-phosphate (PRP) Antigens
Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per milliliter (μg/mL).
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).
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).
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).
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00473668
Brief Title
Non-inferiority of GSK Biologicals' DTPw-HBV/Hib Compared to Two Formulations of GSK Biologicals' DTPw-HBV/Hib
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
June 1, 2007 (undefined)
Primary Completion Date
January 30, 2008 (Actual)
Study Completion Date
January 30, 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Whole Cell Pertussis, Haemophilus Influenzae Type b, Tetanus, Diphtheria, Hepatitis B
Keywords
Hepatitis B, Tetanus, Diphtheria, Pertussis, Haemophilus influenzae type b Vaccines
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
300 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TRITANRIX-HEPB/HIBERIX KFT. GROUP
Arm Type
Experimental
Arm Description
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.
Arm Title
TRITANRIX-HEPB/HIBERIX LD GROUP
Arm Type
Active Comparator
Arm Description
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.
Arm Title
TRITANRIX-HEPB/HIBERIX HD GROUP
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Zilbrix-Hib
Intervention Description
Intramuscular injection, 1 dose
Intervention Type
Biological
Intervention Name(s)
Tritanrix™-HepB/ Hiberix™
Intervention Description
Intramuscular injection, 1 dose
Primary Outcome Measure Information:
Title
Number of Seroprotected Subjects Against Polyribosyl-ribitol-phosphate (PRP) Antigens
Description
A seroprotected subject was defined as a subject with anti-PRP concentrations greater than or equal to (≥) 0.15 microgram per milliliter (µg/mL).
Time Frame
At Month 3
Secondary Outcome Measure Information:
Title
Number of Seroprotected Subjects Against Hepatitis B Surface Antigen (HBs)
Description
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).
Time Frame
At Month 3
Title
Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Antigen
Description
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).
Time Frame
At Month 3
Title
Number of Seroprotected Subjects Against Diphteria (D) With Antibody Concentrations Above the Cut-off
Description
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.
Time Frame
At Month 3
Title
Number of Seropositive Subjects Against Polyribosyl-ribitol-phosphate (PRP) Antigens
Description
Seropositivity was defined as antibody concentrations greater than or equal to (≥) 1 microgram/milliliter (µg/mL).
Time Frame
At Month 3
Title
Number of Seropositive Subjects Against Bordetella Pertussis (BPT) Antigen
Description
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).
Time Frame
At Month 3
Title
Number of Subjects With Vaccine Response to Bordetella Pertussis (BPT) Antigen
Description
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.
Time Frame
At Month 3
Title
Concentration of Antibodies Against Polyribosyl-ribitol-phosphate (PRP) Antigens
Description
Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per milliliter (μg/mL).
Time Frame
At Month 3
Title
Concentration of Antibodies Against Diphtheria (D) and Tetanus (T) Antigens
Description
Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).
Time Frame
At Month 3
Title
Concentration of Antibodies Against Hepatitis B Surface Antigen (HBs)
Description
Concentrations are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL).
Time Frame
At Month 3
Title
Concentration of Antibodies Against Bordetella Pertussis (BPT) Antigen
Description
Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL).
Time Frame
At Month 3
Title
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description
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.
Time Frame
During the 4-day (Day 0-3) follow-up period post-vaccination
Title
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description
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.
Time Frame
During the 4-day (Day 0-3) follow-up period post-vaccination
Title
Number of Subjects With Any Unsolicited Adverse Events (AEs)
Description
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.
Time Frame
During the 31-day (Day 0-30) follow-up period post-vaccination
Title
Number of Subjects With Serious Adverse Events (SAEs)
Description
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.
Time Frame
During the entire study period (Day 0-Month 3)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Weeks
Maximum Age & Unit of Time
8 Weeks
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Bangalore
ZIP/Postal Code
560034
Country
India
Facility Name
GSK Investigational Site
City
Kolkotta
ZIP/Postal Code
700072
Country
India
Facility Name
GSK Investigational Site
City
Varanasi
ZIP/Postal Code
221005
Country
India
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
20950457
Citation
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.
Results Reference
background
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
104977
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
104977
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
104977
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
104977
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
104977
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
104977
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
Non-inferiority of GSK Biologicals' DTPw-HBV/Hib Compared to Two Formulations of GSK Biologicals' DTPw-HBV/Hib
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