Immune Response Post Pry Vaccination of 2 Formulations of DTPw-HBV Vaccine Given With Rotavirus Vaccine to Infants

A Phase III, Partially Blind, Randomized Study to Evaluate the Immunogenicity, Safety and Reactogenicity of GlaxoSmithKline (GSK) Biologicals' Tritanrix™-HepB and GSK Biologicals Kft's DTPw-HBV Vaccines as Compared to Concomitant Administration of Commonwealth Serum Laboratory's (CSL's) DTPw (Triple Antigen™) and GSK Biologicals' HBV (Engerix™-B), When Co-administered With GSK Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Vaccine, to Healthy Infants at 3, 4½ and 6 Months of Age, After a Birth Dose of Hepatitis B Vaccine.

To compare the two formulations of GSK Biologicals' DTPw-HBV vaccine to concomitant administration of CSL's DTPw vaccine and GSK Biologicals' HBV with respect to the antibody response to the diphtheria antigen after a three-dose primary vaccination course.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Biological: Tritanrix™-HepB; Biological: Rotarix™; Drug: Placebo; Biological: Zilbrix™; Biological: Triple Antigen™; Biological: Engerix™-B

Detailed Description

Randomized study with five groups to receive one of the following vaccination regimens:

One of the two formulations of GSK Biologicals' DTPw-HBV + GSK Biologicals' HRV One of the two formulations of GSK Biologicals' DTPw-HBV + Placebo CSL's DTPw + GSK Biologicals' HBV

• Study Type: Interventional
• Enrollment (Actual): 308
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Barnaul, Russian Federation, 656049
    • GSK Investigational Site
  • Ekaterinburg, Russian Federation, 620003
    • GSK Investigational Site
  • Ivanteevka Moscow Region, Russian Federation, 141280
    • GSK Investigational Site
  • Krasnoyarsk, Russian Federation, 660027
    • GSK Investigational Site
  • Moscow, Russian Federation, 119991
    • GSK Investigational Site
  • Moscow, Russian Federation, 129347
    • GSK Investigational Site
  • Samara, Russian Federation, 443021
    • GSK Investigational Site
  • St Petersburg, Russian Federation, 197022
    • GSK Investigational Site
  • Tomsk, Russian Federation, 634 050
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 weeks to 4 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Subjects who the investigator believes that their parent/guardian can and will comply with the requirements of the protocol.
• Administration of one dose of hepatitis B vaccine at birth.
• A male or female between, and including, 11 and 17 weeks of age at the time of the first DTPw vaccination.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.

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.
• Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
• Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days before the first vaccine dose or planned administration during the study period with the exception of oral polio vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing is required)
• 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: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tritanrix™-HepB+Rotarix™ Group; Subjects received 3 doses of Tritanrix™-HepB vaccine at 3, 4.5 and 6 months of age, intramuscularly into the right anterolateral thigh concomitantly with 2 oral doses of Rotarix™ vaccine at 3 and 4.5 months of age.	Biological: Tritanrix™-HepB; GSK Biologicals' combined diphtheria-tetanus-whole cell Bordetella pertussis -hepatitis B vaccine.; Other Names: DTPw-HBV; Biological: Rotarix™; GSK Biologicals' live attenuated human rotavirus vaccine; Other Names: HRV vaccine
Experimental: Tritanrix™-HepB+Placebo Group; Subjects received 3 doses of Tritanrix™-HepB vaccine at 3, 4.5 and 6 months of age, intramuscularly into the right anterolateral thigh concomitantly with 2 oral doses of Placebo for Rotarix™ vaccine at 3 and 4.5 months of age.	Biological: Tritanrix™-HepB; GSK Biologicals' combined diphtheria-tetanus-whole cell Bordetella pertussis -hepatitis B vaccine.; Other Names: DTPw-HBV; Drug: Placebo; Placebo for the Rotarix™ vaccine
Active Comparator: Zilbrix™+Rotarix™ Group; Subjects received 3 doses of Zilbrix™ vaccine at 3, 4.5 and 6 months of age, intramuscularly into the right anterolateral thigh concomitantly with 2 oral doses of Rotarix™ vaccine at 3 and 4.5 months of age.	Biological: Rotarix™; GSK Biologicals' live attenuated human rotavirus vaccine; Other Names: HRV vaccine; Biological: Zilbrix™; GSK Biologicals Kft's combined diphtheria-tetanus whole-cell B. pertussis-hepatitis B vaccine; Other Names: DTPw-HBV Kft
Active Comparator: Zilbrix™+Placebo Group; Subjects received 3 doses of Zilbrix™ vaccine at 3, 4.5 and 6 months of age, intramuscularly into the right anterolateral thigh concomitantly with 2 oral doses of Placebo for Rotarix™ vaccine at 3 and 4.5 months of age.	Drug: Placebo; Placebo for the Rotarix™ vaccine; Biological: Zilbrix™; GSK Biologicals Kft's combined diphtheria-tetanus whole-cell B. pertussis-hepatitis B vaccine; Other Names: DTPw-HBV Kft
Active Comparator: Triple Antigen™+Engerix™-B Group; Subjects received 3 separate doses of Triple Antigen™ and Engerix™-B vaccines at 3, 4.5 and 6 months of age, intramuscularly into the left and right anterolateral thighs, respectively.	Biological: Triple Antigen™; Commonwealth Serum Laboratory's (CSL's) combined diphtheria-tetanus-whole cell B. pertussis vaccine.; Other Names: DTPwcsl vaccine; Biological: Engerix™-B; GSK Biologicals' hepatitis B vaccine; Other Names: HBV vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroprotection Status for Anti-diphteria (Anti-DT) Antibodies	Seroprotection status (SP) defined vaccinated subjects with antibody concentrations greater than or equal to (≥) 0.1 international units per millitre (IU/mL) as assessed by the Enzyme-linked Immunosorbent Assay (ELISA) or ≥ 0.016 IU/mL by neautralization assay on Vero cells in subjects seronegative for ELISA.	At one month post dose 3 [PIII(M4)]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroprotected Subjects for Anti-DT Antibodies as Assessed by ELISA	A seroprotected subject is a vaccinated subject with concentrations ≥ 0.1 IU/mL.	At one month post dose 3 [PIII(M4)]
Number of Seroprotected Subjects for Anti-Hepatitis B (Anti-HBs) Antibodies	A seroprotected subject was defined as a vaccinated subject with antibody concentrations ≥ 10 milli-international units per millilitre (mIU/mL).	At one most post dose 3 [PIII(M4)]
Number of Seropositive Subjects With Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations ≥ the Established Cut-off Values	A seropositive subject was defined as a subject with Anti-BPT antibody concentrations ≥ 15 ELISA units per millilitre (EL.U/mL), as assessed by the Enzyme-Linked Immunosorbent Assay (ELISA).	At one month post dose 3 [PIII(M4)]
Number of Subjects With Vaccine Response to BPT Antigen	Vaccine response (VR) was defined as the appearance of antibodies in subjects seronegative at pre-vaccination and antibody concentrations ≥ the cut-off values post-vaccination in subjects who were seropositive at pre-vaccination.	At one month post dose 3 [PIII(M4)]
Number of Seropositive Subjects With Anti-rotavirus (Anti-RV) Antibodies Above the Cut-off Values	A seropositive subject was defined as a subject with anti-RV antibody concentrations ≥ 20 units per millilitre (U/mL).	At 2.5 months after dose 2 of Rotarix [PIII(M4)]
Number of Seroprotected Subjects for Anti-Tetanus (Anti-T) Antigen	A seroprotected subject was defined as a vaccinated subject with anti-T antibody concentrations ≥ the cut-off value of 0.1 international units per millilitre (IU/mL).	At one month post dose 3 [PIII(M4)]
Number of Seroprotected Subjects for Anti-Poliovirus Types 1, 2, 3 (Anti-Polio 1, 2, 3)	A seroprotected subject was defined as a vaccinated subject with anti-Polio type 1,2 ,3 antibody titers ≥ 8	At one month post dose 3 [PIII(M4)]
Concentrations of Anti-HBs Antibodies	Concentrations of anti-HB, antibodies, expressed as Geometric Mean Concentrations (GMCs), were measured in mIU/mL.	At one month post dose 3 [PIII(M4)]
Concentrations of Anti-DT Antibodies	Concentrations of anti-DT antibodies, expressed as Geometric Mean Concentrations (GMCs), were measured in IU/mL.	At one month post dose 3 [PIII(M4)]
Concentrations of Anti-T Antibodies	Concentrations, expressed as Geometric Mean Concentrations (GMCs), were measured in international units per millillitre (IU/mL).	At one month post dose 3 [PIII(M4)]
Concentrations of Anti-BPT Antibodies	Concentrations, expressed as Geometric Mean Concentrations (GMCs), were measured in EL.U/mL.	At one month post dose 3 [PIII(M4)]
Concentrations of Anti-RV Antibodies	Concentrations, expressed as Geometric Mean Concentrations (GMCs), were measured in U/mL.	At 2.5 months post dose 2 of Rotarix [PIII(M4)]
Anti-Polio Type 1, 2, 3 Antibody Titers	Anti-Polio type 1, 2 and 3 antibody titers were expressed as Geometric Mean Titers (GMTs).	At one month post dose 3 [PIII(M4)]
Number of Subjects With Solicited Local Symptoms	Solicited local symptoms were pain, redness and swelling. Any = occurence of symptom regardless of intensity grade. Grade 3 pain = Significant pain at rest, pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling with a maximum diameter greater than 30 millimeters (mm).	During the 8-Day (Days 0-7) follow-up period
Number of Subjects With Any Solicited General Symptoms	Assessed solicited general symptoms were diarrhea, drowsiness, fever [defined as rectal temperature equal to or above 38.0 degrees Celsius (°C)], irritability, loss of appetite [loss of appet.] and vomiting. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. Grade 3 loss of appetite = symptoms that prevents eating. Grade 3 diarrhea = ≥ 6 looser than normal stools per (/) day. Grade 3 vomiting = ≥ 3 episodes of vomiting/day.	During the 8-day period (Days 0-7) post-vaccination
Number of Subjects With Unsolicited Adverse Events (AEs)	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 (Days 0-30) follow-up period
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.	From Month 0 to Month 4

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

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 (Actual): September 12, 2005
• Primary Completion (Actual): November 1, 2006
• Study Completion (Actual): November 23, 2006

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (Estimate): September 12, 2005

Study Record Updates

• Last Update Posted (Actual): June 6, 2018
• Last Update Submitted That Met QC Criteria: April 26, 2018
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Pertussis; Prophylaxis; Diphtheria; Tetanus; Hepatitis B diseases
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 104021

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. Individual Participant Data Set
   Information identifier: 104021
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 104021
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 104021
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 104021
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 104021
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 104021
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register