Safety and Immunogenicity of a Booster Dose of GSK Biological's Boostrix-Polio Vaccine

Evaluation of GSK Biological's dTpa-IPV Booster Vaccine in Children and Adolescents, 5 Years After Previous dTpa-IPV Boosting.

Subjects aged 9 to 13 years who participated in the 711866/001 study 5 years ago will be evaluated for immune persistence and will receive a combined dTpa-IPV booster dose that will be evaluated in terms of immunogenicity, safety and reactogenicity.

Study Overview

• Status: Completed
• Conditions: Tetanus; Diphtheria; Acellular Pertussis; Poliomyelitis
• Intervention / Treatment: Biological: Boostrix-Polio

• Study Type: Interventional
• Enrollment (Actual): 415
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12627
    • GSK Investigational Site
  • Berlin, Germany, 13507
    • GSK Investigational Site
  • Berlin, Germany, 13355
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Ettenheim, Baden-Wuerttemberg, Germany, 77955
      • GSK Investigational Site
    • Kehl, Baden-Wuerttemberg, Germany, 77694
      • GSK Investigational Site
    • Oberkirch, Baden-Wuerttemberg, Germany, 77704
      • GSK Investigational Site
    • Offenburg, Baden-Wuerttemberg, Germany, 77654
      • GSK Investigational Site
  • Bayern
    • Cham, Bayern, Germany, 93413
      • GSK Investigational Site
    • Kaufering, Bayern, Germany, 86916
      • GSK Investigational Site
    • Landshut, Bayern, Germany, 84032
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 80939
      • GSK Investigational Site
    • Olching, Bayern, Germany, 82140
      • GSK Investigational Site
    • Weilheim, Bayern, Germany, 82362
      • GSK Investigational Site
  • Hessen
    • Eschwege, Hessen, Germany, 37269
      • GSK Investigational Site
    • Koenigstein, Hessen, Germany, 61462
      • GSK Investigational Site
  • Niedersachsen
    • Salzgitter, Niedersachsen, Germany, 38226
      • GSK Investigational Site
    • Wolfenbuettel, Niedersachsen, Germany, 38302
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Erkrath, Nordrhein-Westfalen, Germany, 40699
      • GSK Investigational Site
    • Goch, Nordrhein-Westfalen, Germany, 47574
      • GSK Investigational Site
    • Guetersloh, Nordrhein-Westfalen, Germany, 33332
      • GSK Investigational Site
    • Heiligenhaus, Nordrhein-Westfalen, Germany, 42579
      • GSK Investigational Site
    • Kleve-Materborn, Nordrhein-Westfalen, Germany, 47533
      • GSK Investigational Site
    • Krefeld, Nordrhein-Westfalen, Germany, 47798
      • GSK Investigational Site
    • Loehne, Nordrhein-Westfalen, Germany, 32584
      • GSK Investigational Site
    • Muenster, Nordrhein-Westfalen, Germany, 48159
      • GSK Investigational Site
    • Willich, Nordrhein-Westfalen, Germany, 47877
      • GSK Investigational Site
  • Rheinland-Pfalz
    • Bad Kreuznach, Rheinland-Pfalz, Germany, 55543
      • GSK Investigational Site
    • Frankenthal, Rheinland-Pfalz, Germany, 67227
      • GSK Investigational Site
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • GSK Investigational Site
    • Trier, Rheinland-Pfalz, Germany, 54294
      • GSK Investigational Site
    • Worms, Rheinland-Pfalz, Germany, 67547
      • GSK Investigational Site
    • Worms, Rheinland-Pfalz, Germany, 67549
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • GSK Investigational Site
    • Dresden, Sachsen, Germany, 01169
      • GSK Investigational Site
  • Schleswig-Holstein
    • Brunsbuettel, Schleswig-Holstein, Germany, 25541
      • GSK Investigational Site
    • Flensburg, Schleswig-Holstein, Germany, 24937
      • GSK Investigational Site
    • Flensburg, Schleswig-Holstein, Germany, 24939
      • GSK Investigational Site
    • Flensburg, Schleswig-Holstein, Germany, 24943
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 13 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the investigator believes that they or their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
• A male or female subject who received a booster vaccination with dTpa-IPV or dTpa + IPV in study 711866/001.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Females of childbearing potential at the time of study entry must have a negative pregnancy test prior to administration of the dose of vaccine and are required to be abstinent or to use adequate contraceptive precautions for one month prior to vaccination. Subjects are required to agree to continue such precautions for two months after vaccination.
• Written informed consent obtained from both parents/ guardians of the subject; assent from the subject himself/herself should also be requested whenever possible.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the booster dose of study vaccine, or planned use during the study period.
• Chronic administration (defined as more than 14 days) of immunosuppressant or other immune-modifying drugs within six months prior to the booster dose.
• Administration of a vaccine not foreseen by the study protocol within 30 days prior to vaccination, or planned administration during study period.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
• Previous booster vaccination against tetanus, diphtheria, pertussis, or poliomyelitis since the booster dose received in study 711866/001.
• History of diphtheria, tetanus, pertussis, or poliomyelitis diseases.
• Any confirmed or suspected immunosuppressive or immunodeficiency condition, based on medical history and physical examination.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Administration of immunoglobulin and/or any blood products within the three months preceding the booster dose or planned administration during the study period.
• Occurrence of transient thrombocytopenia or neurological complications following an earlier immunisation against diphtheria and/or tetanus.
• Occurrence of any of the following adverse events (AEs) after a previous administration of a DTP vaccine: hypersensitivity reaction to any component of the vaccine, encephalopathy of unknown aetiology occurring within 7 days following previous vaccination with pertussis-containing vaccine, fever ≥ 40°C within 48 hours of vaccination not due to another identifiable cause, collapse or shock-like state within 48 hours of vaccination
• Persistent, severe, inconsolable screaming or crying lasting >3 hours occurring within 48 hours of receipt of a previous dose of DTP vaccine convulsions with or without fever, occurring within 3 days of vaccination.
• Acute disease at the time of enrolment.
• Pregnant or lactating female.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BOOSTRIX-POLIO GROUP; Healthy male or female subjects aged 9 to 13 years, who were given a single booster dose of Boostrix™-Polio vaccine in the dTpa-IPV-001 (711866/001) study, additionally received a single booster dose of the Boostrix™-Polio vaccine, administered intramuscularly in the deltoid region of the non-dominant arm.	Biological: Boostrix-Polio; A single booster dose of dTpa-IPV vaccine will be administered to all subjects. IM administration in the deltoid muscle of the non-dominant arm.
Experimental: BOOSTRIX + IPV MÉRIEUX GROUP; Healthy male or female subjects aged 9 to 13 years, who were given a single booster dose of Boostrix™ and IPV Mérieux® vaccines in the dTpa-IPV-001 (711866/001) study, additionally received a single booster dose of the Boostrix™-Polio vaccine, administered intramuscularly in the deltoid region of the non-dominant arm.	Biological: Boostrix-Polio; A single booster dose of dTpa-IPV vaccine will be administered to all subjects. IM administration in the deltoid muscle of the non-dominant arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Any Grade 3 Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Grade 3 Pain: Pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.	During the 4-day (Days 0-3) follow-up period after booster vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Any Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.	During the 4-day (Days 0-3) follow-up period after booster vaccination
Number of Subjects With Any Solicited General Symptoms	Assessed solicited general symptoms were fatigue, gastrointestinal, headache and temperature [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade and relationship to vaccination.	During the 4-day (Days 0-3) follow-up period after booster vaccination
Number of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Toxoids	Anti-D and anti-T antibody concnetration greater than or equal to (≥) 0.1 international units per milliliter (IU/mL) and ≥ 1 IU/mL have been assessed by enzyme-linked immunosorbent assay (ELISA). Pre-vaccination sera with ELISA concentrations < 0.1 IU/mL were tested for neutralising antibodies using a Vero-cell neutralisation assay with a 0.016 IU/mL cut-off.	Prior to (Month 0) and one month after (Month 1) booster vaccination
Anti-D and Anti-T Antibody Concentrations	Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).	Prior to (Month 0) and one month after (Month 1) booster vaccination
Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN)	A seropositive subject was defined as a subject with anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 ELISA unit per milliliter (EL.U/ml).	Prior to (Month 0) and one month after (Month 1) booster vaccination
Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations	Antibodies concentrations were presented as geometric mean concentrations (GMCs), expressed in EL.U/mL.	Prior to (Month 0) and one month after (Month 1) booster vaccination
Number of Seroprotected Subjects Against Polio Type 1, 2 and 3 Antigens	A seroprotected subject was defined as a subject with anti-Polio type 1, 2 and 3 antibody titers ≥ the value of 8.	Prior to (Month 0) and one month after (Month 1) booster vaccination
Anti-Polio 1, 2 and 3 Antibody Titers	Antibody titers were presented as geometric mean titers (GMTs).	Prior to (Month 0) and one month after (Month 1) booster vaccination
Number of Subjects With Booster Response to Anti-PT, Anti-FHA and Anti-PRN	Booster vaccine response was defined as appearance of antibodies in subjects who were seronegative at the pre-vaccination time point (i.e. with concentrations < 5 EL.U/mL) or at least 2-fold increase of pre-vaccination antibody concentrations in subjects who were seropositive at the pre-vaccination time point (i.e. with concentrations < 5 EL.U/mL).	One month after booster vaccination (At Month 1)
Number of Subjects With Unsolicited Adverse Events (AEs)	AEs results are presented for all subjects. 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 after booster vaccination
Number of Subjects With Serious Adverse Events (SAEs)	Assessed SAEs include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	During the entire booster period (Month 0 to Month 1)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Mertsola J et al. The safety of repeated administration of Boostrix™, a reduced-antigen-content dTpa booster. Abstract presented at Excellence In Paediatrics (EIP). Florence, Italy, 3-6 December 2009.
• Knuf M, Baine Y, Bianco V, Boutriau D, Miller JM. Antibody persistence and immune memory 15 months after priming with an investigational tetravalent meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) in toddlers and young children. Hum Vaccin Immunother. 2012 Jul;8(7):866-72. doi: 10.4161/hv.20229. Epub 2012 Apr 9.
• Mertsola J et al. The safety of repeated administration of reduced-antigen-content dTpa boosters. Abstract presented at WSPID-6th World Congress. Buenos Aires, Argentina, 19-22 November 2009.
• Knuf M et al. The repeated administration of a reduced antigen content diphtheria, tetanus, acellular pertussis and poliomyelitis vaccine (dTpa-IPV; BoostrixTM IPV) in adolescents. Abstract presented at IDSA. Philadelphia, USA, 29 October- 1 November 2009.
• Knuf M, Vetter V, Celzo F, Ramakrishnan G, Van Der Meeren O, Jacquet JM. Repeated administration of a reduced-antigen-content diphtheria-tetanus-acellular pertussis and poliomyelitis vaccine (dTpa-IPV; Boostrix IPV). Hum Vaccin. 2010 Jul;6(7):554-61. doi: 10.4161/hv.6.7.11760.

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): February 1, 2008
• Primary Completion (Actual): July 8, 2008
• Study Completion (Actual): July 8, 2008

Study Registration Dates

• First Submitted: March 6, 2008
• First Submitted That Met QC Criteria: March 6, 2008
• First Posted (Estimate): March 13, 2008

Study Record Updates

• Last Update Posted (Actual): June 6, 2018
• Last Update Submitted That Met QC Criteria: April 27, 2018
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Booster; vaccine; Pertussis; Diphtheria; Tetanus; Poliomyelitis; DTP
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Neuromuscular Diseases; Central Nervous System Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Enterovirus Infections; Picornaviridae Infections; Spinal Cord Diseases; Clostridium Infections; Corynebacterium Infections; Myelitis; Whooping Cough; Tetanus; Diphtheria; Poliomyelitis
• Other Study ID Numbers: 110947

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: 110947
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 110947
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 110947
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 110947
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 110947
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: 110947
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Annotated Case Report Form
   Information identifier: 110947
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register