Assess Feasibility of an Acellular Pertussis Vaccine (Pa) Given Soon After Birth, Followed by 3-dose Primary Vaccination With the DTPa-HBV-IPV/Hib Vaccine

Assess the Feasibility of an Investigational Vaccination Regimen, Compared to a 3-dose Primary Vaccination With GSK Biologicals' Infanrix Hexa™ (DTPa-HBV-IPV/Hib Vaccine) Following Hepatitis B Vaccination at Birth. Primary Vaccination is Followed in the 2nd Year of Life by a Booster Dose of Infanrix-hexa

This study will assess immunogenicity, safety and reactogenicity of primary and booster vaccination.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Biological: DTPa-HBV-IPV/Hib

Detailed Description

"There will be two groups in this study:

• one group will receive a birth dose of Pa vaccine and 3 doses of DTPa-HBV-IPV/Hib vaccine as primary vaccination and a dose of DTPa-HBV-IPV/Hib vaccine as booster vaccination
• the control group will receive a birth dose of hepatitis B vaccine and 3 doses of DTPa-HBV-IPV/Hib vaccine as primary vaccination and a dose of DTPa-HBV-IPV/Hib vaccine as booster vaccination".

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 days to 5 days (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria For the primary vaccination phase

• Healthy newborn male or female infant 2 to 5 days old at the time of the first vaccination & written informed consent taken from the parents/guardians of the subject
• Born at term (gestational age 37-42 weeks) after an uncomplicated pregnancy
• Birth weight >= 2.5 kg and 5 minute Apgar >= 7
• Mother seronegative for Hepatitis B surface antigen (HBsAg) For the booster vaccination phase
• A healthy male or female between, and including, 12 and 23 months of age at the time of booster vaccination who has completed the primary vaccination course in the primary vaccination phase with written informed consent obtained from the parent or guardian of the subject

Exclusion criteria For the primary vaccination phase

• Mother known or suspected to be seropositive for HIV (testing not required for inclusion)
• Planned use of any investigational or non-registered product (drug or vaccine) other than the study vaccines during the study
• Planned administration of immuno-suppressants or other immune-modifying drugs, administration of immunoglobulins and/or any blood products since birth or planned administration during the study.
• Administration of immunoglobulins and/or any blood products to the mother during pregnancy
• Neonatal jaundice requiring parenteral treatment (light therapy for physiological jaundice is allowed)
• At risk of pneumococcal disease or planning to receive Prevenar™ during the study period
• Administration or planned administration of BCG vaccination during the study period
• Acute disease at the time of vaccination. For the booster vaccination phase
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the booster dose, or planned use during the booster phase.
• Evidence of previous diphtheria, tetanus, pertussis, polio, hepatitis B and/or Hib booster vaccination since the study conclusion visit of the primary vaccination phase.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
• Administration/ planned administration of a vaccine not foreseen by the study protocol, administration/ planned administration of immunoglobulins and/or any blood products during the period starting 30 days before the administration of the booster dose and ending 30 days after the booster dose.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the booster vaccine dose."

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Infanrix hexa Group; Subjects received a dose of hepatitis B vaccine at birth followed by immunization with 3 doses of Infanrix hexa™ (2, 4 and 6 months of age) and one booster dose of Infanrix hexa™ between 12 and 23 months of age. All vaccines were administered by deep intramuscular injection into the left anterolateral thigh.	Biological: DTPa-HBV-IPV/Hib; GSK Biologicals' combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b conjugate vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of seropositive subjects for anti-pertussis toxoids (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies	A seropositive subject was defined a subject with antibody concentrations ≥ 5 EL.U/mL.	At Month 0
Number of seropositive subjects for anti-pertussis toxoids (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies	A seropositive subject was defined a subject with antibody concentrations ≥ 5 EL.U/mL.	At Month 3
Number of seropositive subjects for anti-pertussis toxoids (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies	A seropositive subject was defined a subject with antibody concentrations ≥ 5 EL.U/mL.	At Month 5
Number of seropositive subjects for anti-pertussis toxoids (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies	A seropositive subject was defined a subject with antibody concentrations ≥ 5 EL.U/mL.	At Month 7
Antibody concentrations for anti-pertussis toxoids (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies	Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off of ≥ 5 EL.U/mL.	At Month 0
Antibody concentrations for anti-pertussis toxoids (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies	Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off of ≥ 5 EL.U/mL.	At Month 3
Antibody concentrations for anti-pertussis toxoids (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies	Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off of ≥ 5 EL.U/mL.	At Month 5
Antibody concentrations for anti-pertussis toxoids (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies	Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off of ≥ 5 EL.U/mL.	At Month 7
Number of seropositive subjects for anti-pertussis toxoids (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies	A seropositive subject was defined a subject with antibody concentrations ≥ 5 EL.U/mL.	At Month 1 Post-Booster
Antibody concentrations for anti-pertussis toxoids (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies	Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off of ≥ 5 EL.U/mL.	At Month 1 Post-Booster
Modified vaccine response for anti-pertussis toxoids (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies	Modified vaccine response was defined as: For initially seronegative subjects, antibody concentration 5 EL.U/mL at one month after the third dose of Infanrix hexa™. For initially seropositive subjects: antibody concentration at one month post vaccination 0.25 fold the pre-vaccination antibody concentration.	At Month 7
Modified vaccine response for anti-pertussis toxoids (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies	Modified vaccine response was defined as: For initially seronegative subjects, antibody concentration 5 EL.U/mL at one month after the third dose of Infanrix hexa™. For initially seropositive subjects: antibody concentration at one month post vaccination 0.25 fold the pre-vaccination antibody concentration.	At Month 1 Post-Booster
Number of seroprotected subjects for anti-Hepatitis B surface antigen (anti-HBs) antibodies	A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.	At Month 7
Number of seroprotected subjects for anti-Hepatitis B surface antigen (anti-HBs) antibodies	A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.	At pre-booster vaccination (Month 0 BST)
Number of seroprotected subjects for anti-Hepatitis B surface antigen (anti-HBs) antibodies	A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.	At Month 1 post-booster vaccination
Antibody concentrations for anti-Hepatitis B surface antigen (anti-HBs) antibodies	Concentrations were expressed as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 10 mIU/mL.	At Month 7
Antibody concentrations for anti-Hepatitis B surface antigen (anti-HBs) antibodies	Concentrations were expressed as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 10 mIU/mL.	At pre-booster vaccination (Month 0 BST)
Antibody concentrations for anti-Hepatitis B surface antigen (anti-HBs) antibodies	Concentrations were expressed as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 10 mIU/mL.	At Month 1 post-booster vaccination
Number of seroprotected subjects for anti-diphtheria (anti-D) and anti-tetanus (anti-T) antibodies	A seroprotected subject was defined as a subject with anti-D and anti-T antibody concentrations ≥ 0.1 IU/mL.	At Month 7
Number of seroprotected subjects for anti-diphtheria (anti-D) and anti-tetanus (anti-T) antibodies	A seroprotected subject was defined as a subject with anti-D and anti-T antibody concentrations ≥ 0.1 IU/mL.	At pre-booster vaccination (Month 0 BST)
Number of seroprotected subjects for anti-diphtheria (anti-D) and anti-tetanus (anti-T) antibodies	A seroprotected subject was defined as a subject with anti-D and anti-T antibody concentrations ≥ 0.1 IU/mL.	At Month 1 post-booster vaccination
Antibody concentrations for anti-diphtheria (anti-D) and anti-tetanus (anti-T) antibodies	Concentrations were expressed as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 0.1 IU/mL.	At Month 7
Antibody concentrations for anti-diphtheria (anti-D) and anti-tetanus (anti-T) antibodies	Concentrations were expressed as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 0.1 IU/mL.	At pre-booster vaccination (Month 0 BST)
Antibody concentrations for anti-diphtheria (anti-D) and anti-tetanus (anti-T) antibodies	Concentrations were expressed as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 0.1 IU/mL.	At Month 1 post-booster vaccination
Number of seroprotected subjects for anti-polyribosyl ribitol phosphate (anti-PRP)	A seroprotected subject was defined as a subject with anti-D and anti-T antibody concentrations ≥ 0.15 g/mL.	At Month 7
Number of seroprotected subjects for anti-polyribosyl ribitol phosphate (anti-PRP)	A seroprotected subject was defined as a subject with anti-D and anti-T antibody concentrations ≥ 0.15 g/mL.	At pre-booster vaccination (Month 0 BST)
Number of seroprotected subjects for anti-polyribosyl ribitol phosphate (anti-PRP)	A seroprotected subject was defined as a subject with anti-D and anti-T antibody concentrations ≥ 0.15 g/mL.	At Month 1 post-booster vaccination
Antibody concentrations for anti-polyribosyl ribitol phosphate (anti-PRP)	Concentrations were expressed as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 0.15 g/mL.	At Month 7
Antibody concentrations for anti-polyribosyl ribitol phosphate (anti-PRP)	Concentrations were expressed as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 0.15 g/mL.	At pre-booster vaccination (Month 0 BST)
Antibody concentrations for anti-polyribosyl ribitol phosphate (anti-PRP)	Concentrations were expressed as geometric mean concentrations (GMCs) for the seroprotection cut-off of ≥ 0.15 g/mL.	At Month 1 post-booster vaccination
Number of subjects with solicited general symptoms	The solicited local symptoms assessed were Drowsiness, Temperature (Fever), Irritability and Loss of appetite. Temperature = Fever ≥ 38.0 °C. Grade 3 drowsiness = drowsiness that prevented normal activity; Grade 3 irritability = crying that could not be comforted/prevented normal activity; Grade 3 loss of appetite = not eating at all; Grade 3 Temperature = > 39.5 °C. Related = symptoms considered by the investigator to have a causal relationship to vaccination.	During the 8-day (Day 0-Day 7) follow-up period after the any dose and booster vaccination
Number of subjects with unsolicited adverse events (AES)	An AE was defined as 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.	Occurring within Day 0-30 following primary and booster vaccination

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Knuf M, Schmitt HJ, Wolter J, Schuerman L, Jacquet JM, Kieninger D, Siegrist CA, Zepp F. Neonatal vaccination with an acellular pertussis vaccine accelerates the acquisition of pertussis antibodies in infants. J Pediatr. 2008 May;152(5):655-60, 660.e1. doi: 10.1016/j.jpeds.2007.09.034. Epub 2007 Nov 19.
• Knuf M, Schmitt HJ, Jacquet JM, Collard A, Kieninger D, Meyer CU, Siegrist CA, Zepp F. Booster vaccination after neonatal priming with acellular pertussis vaccine. J Pediatr. 2010 Apr;156(4):675-8. doi: 10.1016/j.jpeds.2009.12.019.

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: July 1, 2004
• Primary Completion (Actual): April 1, 2006
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: February 9, 2006
• First Submitted That Met QC Criteria: February 9, 2006
• First Posted (Estimate): February 10, 2006

Study Record Updates

• Last Update Posted (Estimate): February 8, 2017
• Last Update Submitted That Met QC Criteria: February 6, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis
• Other Study ID Numbers: 210602-002; 105752 (Other Identifier: GSK)

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. Study Protocol
   Information identifier: 210602-002
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 210602-002
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 210602-002
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 210602-002
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 210602-002
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 210602-002
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register