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A Study Exploring Whooping Cough Protection in Children and Adults (BERT)

Primary Purpose

Pertussis

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Boostrix®-IPV combination vaccine
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Pertussis

Eligibility Criteria

7 Years - 70 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Normal general health
  • Within the right age group for the cohort
  • Received all regular vaccines for their age group according to the Dutch NIP, UK NIP or Finnish NIP; a copy of the vaccination booklet will be included in the participant's documents. If booklet is not available for cohorts A, B and C, vaccination status will be checked although, for cohort C and D this booklet might not be available due to their age;
  • Provision of written informed consent
  • Willing to adhere to the protocol and be available during the study period.

Exclusion Criteria:

  • Present evidence of serious disease(s) within the last 3 months before inclusion requiring immunosuppressive or immune modulating medical treatment, such as systemic corticosteroids, that might interfere with the results of the study;
  • Chronic infection
  • Known or suspected immune deficiency;
  • History of any neurologic disorder, including epilepsy;
  • Previous administration of serum products (including immunoglobulins) within 6 months before vaccination and blood sampling;
  • Known and/or suspected allergy to any of the vaccine components (by medical history);
  • Occurrence of a serious adverse events (SAEs) after primary DTwP-IPV vaccination, DTaP-IPV vaccination or any other vaccination (by medical history);
  • Vaccination with any other pertussis vaccine other than those described in the inclusion criteria (i.e. only according to NIP)
  • Vaccination with any other DT-IPV vaccine in the last 5 years, a DT-IPV vaccination according to NIP in cohort B is not an exclusion criterion;
  • Children between 8 and 10 years of age eligible for cohort A in the Netherlands who have already received the diphtheria and tetanus toxoid vaccine (DT)-IPV booster vaccination according to Dutch NIP around 9 years of age;
  • Mixed wP and aP priming within a participant, cohort B;
  • Pregnancy. Detailed considerations for this exclusion criteria in section 4.6.

Temporary exclusion criteria

  • If a participant has a severe acute (infectious) illness or fever (>38°C) within 14 days prior to T0, participation will be postponed or cancelled. In case the participant has fever within 2 days before sampling at T4 or T5, the appointment will be postponed for 4 days, if possible.
  • Antibiotic use within 14 days of enrolment.
  • Any vaccination within a month before enrolment.

Sites / Locations

  • University of Turku
  • Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM)
  • Centre for Clinical Vaccinology & Tropical Medicine (CCVTM)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Children aged between 7-10 years of age

Children aged between 11-15 years of age

Adults aged between 20-34 years of age

Adults aged between 60-70 years of age

Arm Description

Healthy children from 7 up to 10 years of age, determined by date of birth (dd/mm/yyyy), at the time of the first visit. Male + female, approximately equally distributed, n = 36 in each country. They will receive Boostrix®-IPV combination vaccine.

Healthy children from 11 up to 15 years of age, determined by date of birth (dd/mm/yyyy), at the time of the first visit. Male + female, approximately equally distributed, n = 36 in each country aiming for comparable numbers of participants with aP vs wP vaccination background. They will receive Boostrix®-IPV combination vaccine.

Healthy young adults from 20 up to 34 years of age, determined by date of birth (dd/mm/yyyy), at the time of the first visit. Male + female, approximately equally distributed, n = 25 in each country. They will receive Boostrix®-IPV combination vaccine.

Older adults from 60 up to 70 years of age determined by date of birth (dd/mm/yyyy), at the time of the first visit. Male + female, approximately equally distributed, n = 25 in each country. They will receive Boostrix®-IPV combination vaccine.

Outcomes

Primary Outcome Measures

Change from baseline of pertussis toxin-specific IgG antibody levels to 28 days after vaccination

Secondary Outcome Measures

Amount of pertussis toxin (PT) specific IgG antibody one year after vaccination with Boostrix-IPV
Change from baseline in pertussis toxin (PT) specific IgG-subclasses and avidity levels to 28 days and 1 year after vaccination with Boostrix-IPV
Change from baseline of antigen-specific IgG antibody levels against other pertussis vaccine antigens (such as FHA) and non-pertussis vaccine antigens (such as diptheria and tetanus toxoid) to 28 days and 1 year after vaccination with Boostrix-IPV
Change from baseline of functional pertussis-specific antibody levels to 28 days and 1 year after vaccination with Boostrix-IPV
Change from baseline of B cell responses against Bordetella pertussis vaccine proteins after vaccination with Boostrix-IPV
Antigen-specific memory B cell responses against B-pertussis vaccine proteins
Change from baseline of pertussis antigen-specific T helper responses to 14 days, 28 days and 1 year after vaccination with Boostrix-IPV
To describe the effect on an aP booster on the specific T cell immune response in different age groups that have been initially vaccinated with either a whole cell or acellular vaccine
Identify markers in biological samples collected in the Biobank (library of samples) that show changes in immunity to pertussis
Use of novel exploratory immunoassays on stored samples to identify biomarkers or lasting memory or waning immunity to pertussis.

Full Information

First Posted
April 23, 2018
Last Updated
January 7, 2021
Sponsor
University of Oxford
Collaborators
National Institute for Public Health and the Environment (RIVM), University of Turku
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1. Study Identification

Unique Protocol Identification Number
NCT03697798
Brief Title
A Study Exploring Whooping Cough Protection in Children and Adults
Acronym
BERT
Official Title
Immunological Effects of an Acellular Pertussis Booster Vaccination in Children, Young Adults and Elderly With Different Immunisation Background. An International Study in Finland, the Netherlands and the United Kingdom
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
April 18, 2018 (Actual)
Primary Completion Date
January 14, 2020 (Actual)
Study Completion Date
January 14, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
Collaborators
National Institute for Public Health and the Environment (RIVM), University of Turku

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study aims to investigate the effects of aP booster vaccination in children, young adults and elderly on the (long-term) immune response to B. pertussis in three European countries with a different epidemiological background and primary vaccination schedule for pertussis.
Detailed Description
The study will be performed in three European countries (UK, Finland and the Netherlands) with a different epidemiological background for pertussis incidence and different age groups will have had different primary schedules with whole cell pertussis (wP) or aP vaccines in their first year of life. Long-term memory responses will be analysed following aP booster vaccination including a detailed assessment of antigen-specific B and T cell responses, serology assays for pertussis antigens and the effect of booster vaccination on dynamic changes in immune cell subsets and gene transcription. There will be four cohorts of healthy volunteers: Cohort A - children aged between 7-10 years Cohort B - children aged between 11-15 years Cohort C - adults aged between 20 to 34 years Cohort D - adults aged between 60-70 years Participants will receive one injection of reduced diphtheria toxoid, tetanus toxoid and reduced acellular pertussis vaccine (dTap)-IPV, (Boostrix® IPV, GlaxoSmithKline (GSK)) combination vaccine intramuscularly in the upper arm. Children (cohorts A and B) will be asked to donate blood four times at different time points, and young and older adults (cohorts C and D) will be asked to donate blood at set time points five times in total over the 12 months duration of the study. The time points will be: Timepoint 0 - day of vaccination Timepoint 1 - 1 day after T0 +/- 4 hours Timepoint 2 - 7 days after T0 +/- 1 day Timepoint 3 - 14 days after T0 +/- 4 days Timepoint 4 - 28 days after T0 +/- 4 days Timepoint 5 - 1 year after T0 +/- 4 weeks

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pertussis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
122 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Children aged between 7-10 years of age
Arm Type
Active Comparator
Arm Description
Healthy children from 7 up to 10 years of age, determined by date of birth (dd/mm/yyyy), at the time of the first visit. Male + female, approximately equally distributed, n = 36 in each country. They will receive Boostrix®-IPV combination vaccine.
Arm Title
Children aged between 11-15 years of age
Arm Type
Active Comparator
Arm Description
Healthy children from 11 up to 15 years of age, determined by date of birth (dd/mm/yyyy), at the time of the first visit. Male + female, approximately equally distributed, n = 36 in each country aiming for comparable numbers of participants with aP vs wP vaccination background. They will receive Boostrix®-IPV combination vaccine.
Arm Title
Adults aged between 20-34 years of age
Arm Type
Active Comparator
Arm Description
Healthy young adults from 20 up to 34 years of age, determined by date of birth (dd/mm/yyyy), at the time of the first visit. Male + female, approximately equally distributed, n = 25 in each country. They will receive Boostrix®-IPV combination vaccine.
Arm Title
Adults aged between 60-70 years of age
Arm Type
Active Comparator
Arm Description
Older adults from 60 up to 70 years of age determined by date of birth (dd/mm/yyyy), at the time of the first visit. Male + female, approximately equally distributed, n = 25 in each country. They will receive Boostrix®-IPV combination vaccine.
Intervention Type
Biological
Intervention Name(s)
Boostrix®-IPV combination vaccine
Intervention Description
A licensed aP (acellular) booster vaccine developed by GlaxoSmithKline.
Primary Outcome Measure Information:
Title
Change from baseline of pertussis toxin-specific IgG antibody levels to 28 days after vaccination
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Amount of pertussis toxin (PT) specific IgG antibody one year after vaccination with Boostrix-IPV
Time Frame
1 year
Title
Change from baseline in pertussis toxin (PT) specific IgG-subclasses and avidity levels to 28 days and 1 year after vaccination with Boostrix-IPV
Time Frame
28 days and 1 year
Title
Change from baseline of antigen-specific IgG antibody levels against other pertussis vaccine antigens (such as FHA) and non-pertussis vaccine antigens (such as diptheria and tetanus toxoid) to 28 days and 1 year after vaccination with Boostrix-IPV
Time Frame
28 days and 1 year
Title
Change from baseline of functional pertussis-specific antibody levels to 28 days and 1 year after vaccination with Boostrix-IPV
Time Frame
28 days and 1 year
Title
Change from baseline of B cell responses against Bordetella pertussis vaccine proteins after vaccination with Boostrix-IPV
Description
Antigen-specific memory B cell responses against B-pertussis vaccine proteins
Time Frame
7 days, 28 days and 1 year
Title
Change from baseline of pertussis antigen-specific T helper responses to 14 days, 28 days and 1 year after vaccination with Boostrix-IPV
Description
To describe the effect on an aP booster on the specific T cell immune response in different age groups that have been initially vaccinated with either a whole cell or acellular vaccine
Time Frame
14 days, 28 days and 1 year
Title
Identify markers in biological samples collected in the Biobank (library of samples) that show changes in immunity to pertussis
Description
Use of novel exploratory immunoassays on stored samples to identify biomarkers or lasting memory or waning immunity to pertussis.
Time Frame
1 year although samples will be stored up to 10 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Normal general health Within the right age group for the cohort Received all regular vaccines for their age group according to the Dutch NIP, UK NIP or Finnish NIP; a copy of the vaccination booklet will be included in the participant's documents. If booklet is not available for cohorts A, B and C, vaccination status will be checked although, for cohort C and D this booklet might not be available due to their age; Provision of written informed consent Willing to adhere to the protocol and be available during the study period. Exclusion Criteria: Present evidence of serious disease(s) within the last 3 months before inclusion requiring immunosuppressive or immune modulating medical treatment, such as systemic corticosteroids, that might interfere with the results of the study; Chronic infection Known or suspected immune deficiency; History of any neurologic disorder, including epilepsy; Previous administration of serum products (including immunoglobulins) within 6 months before vaccination and blood sampling; Known and/or suspected allergy to any of the vaccine components (by medical history); Occurrence of a serious adverse events (SAEs) after primary DTwP-IPV vaccination, DTaP-IPV vaccination or any other vaccination (by medical history); Vaccination with any other pertussis vaccine other than those described in the inclusion criteria (i.e. only according to NIP) Vaccination with any other DT-IPV vaccine in the last 5 years, a DT-IPV vaccination according to NIP in cohort B is not an exclusion criterion; Children between 8 and 10 years of age eligible for cohort A in the Netherlands who have already received the diphtheria and tetanus toxoid vaccine (DT)-IPV booster vaccination according to Dutch NIP around 9 years of age; Mixed wP and aP priming within a participant, cohort B; Pregnancy. Detailed considerations for this exclusion criteria in section 4.6. Temporary exclusion criteria If a participant has a severe acute (infectious) illness or fever (>38°C) within 14 days prior to T0, participation will be postponed or cancelled. In case the participant has fever within 2 days before sampling at T4 or T5, the appointment will be postponed for 4 days, if possible. Antibiotic use within 14 days of enrolment. Any vaccination within a month before enrolment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr Marlies van Houten
Organizational Affiliation
Spaarne Hospital, Hoofddorp
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Prof. dr. Jussi Mertsola
Organizational Affiliation
Turku University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dr Dominic Kelly
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Turku
City
Turku
ZIP/Postal Code
FI-20014
Country
Finland
Facility Name
Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM)
City
Bilthoven
ZIP/Postal Code
3721 MA
Country
Netherlands
Facility Name
Centre for Clinical Vaccinology & Tropical Medicine (CCVTM)
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7LE
Country
United Kingdom

12. IPD Sharing Statement

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A Study Exploring Whooping Cough Protection in Children and Adults

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