Immunogenicity, Safety & Reactogenicity of GSK Vaccine Tritanrix™-HepB/Hib2.5 Compared to GSK Vaccine Tritanrix™-HepB/Hiberix™

A Phase II, Double-blind, Randomized Study to Compare the Immunogenicity, Safety and Reactogenicity of GlaxoSmithKline (GSK) Biologicals' Tritanrix™-HepB/Hib2.5 to GSK Biologicals' Tritanrix™-HepB/Hiberix™ When Administered as a Three-dose Primary Vaccination Course to Healthy Infants at 6, 10 and 14 Weeks of Age. A Dose of Unconjugated Hib Vaccine (Plain PRP Booster) Will be Administered at the Age of 10 Months to 50% of the Subjects

In order to reduce the amount of thiomersal in its vaccines, GSK Biologicals has developed a DTPw-HBV vaccine with low thiomersal content (Tritanrix™- HepB low thio). This vaccine is to be used in combination with a Hib low dose vaccine containing 2.5µg of PRP antigen (Hib 2.5). The purpose of this study is to generate clinical data with Tritanrix™-HepB low thio vaccine when extemporaneously mixed with Hib 2.5 vaccine. The control group will receive Tritanrix™-HepB/Hiberix™.

Subjects received primary vaccination in study 208108/091 (double blind). Of these subjects 50% were randomised to participate in the PRP challenge study (208108/092) (open), and all subjects will be invited to participate in a booster study DTPWHBV=HIB2.5-093 (101477).

Study Overview

• Status: Completed
• Conditions: Haemophilus Influenzae Type b
• Intervention / Treatment: Biological: Tritanrix™-HepB low thio /; Biological: Hib 2.5; Biological: Unconjugated Hib vaccine (plain PRP); Biological: Tritanrix™-HepB; Biological: Hiberix™

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 2

Contacts and Locations

Study Locations

• Philippines
  • Muntinlupa, Philippines, 1781
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 month (Child)
• Accepts Healthy Volunteers: Yes
• 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.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.
• Born after a gestation period of 36 to 42 weeks.
• Born to a mother proven seronegative for HBsAg.

Exclusion Criteria:

• Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days before each dose of vaccine, with the exception of oral polio vaccine (OPV).
• Bacille Calmette-Guérin (BCG) vaccine received after the first 2 weeks of life.
• Use of any investigational or non-registered 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.
• Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
• Previous vaccination against diphtheria, tetanus, pertussis, hepatitis B and/or Hib.
• History of, or intercurrent, diphtheria, tetanus, pertussis, hepatitis B and/or Hib disease.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
• A family history of congenital or hereditary immunodeficiency.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Major congenital defects or serious chronic illness.
• History of any neurologic disorders or seizures.
• Acute disease at the time of enrolment.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or history.
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
• Other conditions which in the opinion of the investigator may potentially interfere with interpretation of study outcomes.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A	Biological: Tritanrix™-HepB low thio /; One dose as intramuscular injection at 6, 10 and 14 weeks of age.; Biological: Hib 2.5; One dose as intramuscular injection at 6, 10 and 14 weeks of age.; Biological: Unconjugated Hib vaccine (plain PRP); One dose as intramuscular injection at 10 months of age
Active Comparator: Group B	Biological: Unconjugated Hib vaccine (plain PRP); One dose as intramuscular injection at 10 months of age; Biological: Tritanrix™-HepB; One dose as intramuscular injection at 6, 10 and 14 weeks of age.; Biological: Hiberix™; One dose as intramuscular injection at 6, 10 and 14 weeks of age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
anti-PRP antibody concentration above a protocol defined cut-off value.	One month after the third dose of the primary vaccination course.

Secondary Outcome Measures

Outcome Measure	Time Frame
Occurrence of solicited symptoms	During the 4-day follow-up period after each dose
anti-HBs antibody concentration	One month after the third dose of the primary vaccination course
anti-PRP antibody concentration	One month after the third dose of the primary vaccination course
anti-tetanus antibody concentration	One month after the third dose of the primary vaccination course
anti-diphtheria antibody concentration	One month after the third dose of the primary vaccination course
anti-Bordetella pertussis (BPT) antibody concentration	One month after the third dose of the primary vaccination course
Vaccine response to Bordetella pertussis antigen.	One month after the third dose of the primary vaccination course
Seropositivity/seroprotection rates and GMCs for antibodies against all vaccine antigens	Before the first dose of the primary vaccination course
anti-PRP antibody concentration	Before and one month after the plain PRP challenge dose.
Occurrence of unsolicited symptoms	During the 31-day follow-up period after each dose
Occurrence of serious adverse events	Over the full course of the study

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Gatchalian SR, Ramakrishnan G, Bock HL, Lefevre I, Jacquet JM. Immunogenicity, reactogenicity and safety of three-dose primary and booster vaccination with combined diphtheria-tetanus-whole-cell pertussis-hepatitis B-reduced antigen content Haemophilus influenzae type b vaccine in Filipino children. Hum Vaccin. 2010 Aug;6(8):664-72. doi: 10.4161/hv.6.8.12155.

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: August 1, 2003
• Primary Completion (Actual): January 1, 2004
• Study Completion (Actual): August 1, 2004

Study Registration Dates

• First Submitted: February 2, 2010
• First Submitted That Met QC Criteria: February 2, 2010
• First Posted (Estimate): February 3, 2010

Study Record Updates

• Last Update Posted (Estimate): September 9, 2016
• Last Update Submitted That Met QC Criteria: September 8, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Hepatitis B; Pertussis; Diphtheria; Tetanus; Haemophilus influenzae type b; Hib vaccine; Hiberix™; DTPw-HBV vaccine; Tritanrix™-HepB
• Other Study ID Numbers: 208108/091; 208108/092 (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. Dataset Specification
   Information identifier: 208108/091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 208108/091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register. The results of this study 208108/091 are summarised with study 208108/092 on the GSK Clinical Study Register.
3. Statistical Analysis Plan
   Information identifier: 208108/091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 208108/091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 208108/091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 208108/091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register