A Study Exploring Whooping Cough Protection in Children and Adults

Pertussis Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03697798
• Other study ID #: OVG 2016/05
• Status: Completed
• Phase: Phase 4
• Start date: April 18, 2018
• Est. completion date: January 14, 2020

Study information

• Verified date: January 2021
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: January 14, 2020
• Est. primary completion date: January 14, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 7 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pertussis
• Whooping Cough

Intervention

Biological:
• Boostrix®-IPV combination vaccine
A licensed aP (acellular) booster vaccine developed by GlaxoSmithKline.

Locations

Country	Name	City	State
Finland	University of Turku	Turku
Netherlands	Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM)	Bilthoven
United Kingdom	Centre for Clinical Vaccinology & Tropical Medicine (CCVTM)	Oxford	Oxfordshire

Sponsors (3)

Lead Sponsor	Collaborator
University of Oxford	National Institute for Public Health and the Environment (RIVM), University of Turku

Countries where clinical trial is conducted

Finland,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline of pertussis toxin-specific IgG antibody levels to 28 days after vaccination		28 days
Secondary	Amount of pertussis toxin (PT) specific IgG antibody one year after vaccination with Boostrix-IPV		1 year
Secondary	Change from baseline in pertussis toxin (PT) specific IgG-subclasses and avidity levels to 28 days and 1 year after vaccination with Boostrix-IPV		28 days and 1 year
Secondary	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		28 days and 1 year
Secondary	Change from baseline of functional pertussis-specific antibody levels to 28 days and 1 year after vaccination with Boostrix-IPV		28 days and 1 year
Secondary	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	7 days, 28 days and 1 year
Secondary	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	14 days, 28 days and 1 year
Secondary	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.	1 year although samples will be stored up to 10 years