Placebo Controlled Study to Generate Data Characterising Safety Parameters and Immune Responses

NCT ID: NCT02555540

Last Updated: 2022-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-24

Study Completion Date

2016-12-15

Brief Summary

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The purpose of this protocol is to generate a set of data that will be analysed by integrated systems biology approach, for validation in subsequent clinical trials or in animal models.

240 healthy participants (18-45y) will be enrolled, 200 will be administered a dose of Boostrix on Day 0, 20 will receive a placebo on Day 0.

Detailed Description

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This study is part of the BIOVACSAFE project, a 5-year project funded by the Innovative Medicine Initiative, which will undertake a series of correlated clinical studies that will apply and develop technologies to generate clinical data on inflammation with licensed vaccines as benchmarks, and identify biomarkers to predict acceptable reactogenicity, for correlation with standardized clinical readouts and inflammatory markers assessed in natural infections.

The purpose of this protocol is to generate data to undergo integrated systems biology analysis to validate biomarkers identified in the exploratory studies conducted previously or to identify new biomarkers of responses to immunisation

The data set will include data characterising:

1. Physiological responses at various time points after immunisation by measuring:

* Local and systemic vaccine-related clinical events.
* Haematology (blood counts and ESR) and biochemistry parameters.
2. Innate and adaptive immune responses including:

* Innate immune activation detected by global gene expression in whole blood
* Adaptive humoral immunity determined by the quantification antibodies directed against Tetanus toxoid (TT), Diphteria toxoid (DT), Pertussis toxin (PT), Fimbrial haemagglutinin (FHA) and Pertactin (PTN).
* Adaptive immune activation detected by gene pathway activation in whole blood
* Metabolic responses as detected by metabolic gene expression and pathway activation in whole blood
* Innate and adaptive immune activation detected by measuring the concentration of selected soluble mediators in serum including: chemokines and cytokines and acute phase proteins
* As an exploratory endpoint, the adaptive cellular immune response will be evaluated via counting vaccine antigen-specific Cluster of Differentiation 4 (CD4)+ T cells expressing activation markers and/or cytokines following in vitro stimulation and analysis by flow cytometry (and or CyTOF).
3. Genetic testing of subjects when deemed necessary (genetic testing analysis may be SNP (single nucleotide polymorphism) analysis or full genome analysis).
4. Correlations in changes in innate immune activation and metabolism with adverse events, haematology and biochemistry panels, genotype and physiological assessments

The investigators will biobank all samples for the duration of the BIOVACSAFE programme so that they can selectively analyse different samples and different time points depending on the results generated, principally from the gene expression analysis of whole blood.

Conditions

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Prevention of Infections With Bordetella Pertussis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Boostrix, Male, >/= 5 years, D2 visit

25 male subjects who have received their last dT(Pa) vaccine at least 5 years ago, and who have the Visit 2 on 'Day 2'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 2 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type ACTIVE_COMPARATOR

Boostrix

Intervention Type BIOLOGICAL

Randomised assignment

Boostrix, Male, >/= 5 years, D3 visit

25 male subjects who have received their last dT(Pa) vaccine at least 5 years ago, and who have the Visit 2 on 'Day 3'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 3 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type ACTIVE_COMPARATOR

Boostrix

Intervention Type BIOLOGICAL

Randomised assignment

Boostrix, Female, >/= 5 years, D2 visit

25 female subjects who have received their last dT(Pa) vaccine at least 5 years ago, and who have the Visit 2 on 'Day 2'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 2 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type ACTIVE_COMPARATOR

Boostrix

Intervention Type BIOLOGICAL

Randomised assignment

Boostrix, Female, >/= 5 years, D3 visit

25 female subjects who have received their last dT(Pa) vaccine at least 5 years ago, and who have the Visit 2 on 'Day 3'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 3 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type ACTIVE_COMPARATOR

Boostrix

Intervention Type BIOLOGICAL

Randomised assignment

Placebo, Male, >/= 5 years, D2 visit

5 male subjects who have received their last dT(Pa) vaccine at least 5 years ago, and who have the Visit 2 on 'Day 2'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 2 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type PLACEBO_COMPARATOR

Placebo (Saline)

Intervention Type BIOLOGICAL

Randomised assignment

Placebo, Male, >/= 5 years, D3 visit

5 male subjects who have received their last dT(Pa) vaccine at least 5 years ago, and who have the Visit 2 on 'Day 3'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 3 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type PLACEBO_COMPARATOR

Placebo (Saline)

Intervention Type BIOLOGICAL

Randomised assignment

Placebo, Female, >/= 5 years, D2 visit

5 female subjects who have received their last dT(Pa) vaccine at least 5 years ago, and who have the Visit 2 on 'Day 2'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 2 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type PLACEBO_COMPARATOR

Placebo (Saline)

Intervention Type BIOLOGICAL

Randomised assignment

Placebo, Female, >/= 5 years, D3 visit

5 female subjects who have received their last dT(Pa) vaccine at least 5 years ago, and who have the Visit 2 on 'Day 3'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 3 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type PLACEBO_COMPARATOR

Placebo (Saline)

Intervention Type BIOLOGICAL

Randomised assignment

Boostrix, Male, <5 years, D2 visit

25 male subjects who have received their last dT(Pa) vaccine between 5 years and 6 months ago, and who have the Visit 2 on 'Day 2'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 2 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type ACTIVE_COMPARATOR

Boostrix

Intervention Type BIOLOGICAL

Randomised assignment

Boostrix, Male, <5 years, D3 visit

25 male subjects who have received their last dT(Pa) vaccine between 5 years and 6 months ago, and who have the Visit 2 on 'Day 3'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 3 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type ACTIVE_COMPARATOR

Boostrix

Intervention Type BIOLOGICAL

Randomised assignment

Boostrix, Female, <5 years, D2 visit

25 female subjects who have received their last dT(Pa) vaccine between 5 years and 6 months ago, and who have the Visit 2 on 'Day 2'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 2 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type ACTIVE_COMPARATOR

Boostrix

Intervention Type BIOLOGICAL

Randomised assignment

Boostrix, Female, <5 years, D3 visit

25 female subjects who have received their last dT(Pa) vaccine between 5 years and 6 months ago, and who have the Visit 2 on 'Day 3'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 3 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type ACTIVE_COMPARATOR

Boostrix

Intervention Type BIOLOGICAL

Randomised assignment

Placebo, Male, <5 years, D2 visit

5 male subjects who have received their last dT(Pa) vaccine between 5 years and 6 months ago, and who have the Visit 2 on 'Day 2'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 2 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type PLACEBO_COMPARATOR

Placebo (Saline)

Intervention Type BIOLOGICAL

Randomised assignment

Placebo, Male, <5 years, D3 visit

5 male subjects who have received their last dT(Pa) vaccine between 5 years and 6 months ago, and who have the Visit 2 on 'Day 3'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 3 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type PLACEBO_COMPARATOR

Placebo (Saline)

Intervention Type BIOLOGICAL

Randomised assignment

Placebo, Female, <5 years, D2 visit

5 female subjects who have received their last dT(Pa) vaccine between 5 years and 6 months ago, and who have the Visit 2 on 'Day 2'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 2 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type PLACEBO_COMPARATOR

Placebo (Saline)

Intervention Type BIOLOGICAL

Randomised assignment

Placebo, Female, <5 years, D3 visit

5 female subjects who have received their last dT(Pa) vaccine between 5 years and 6 months ago, and who have the Visit 2 on 'Day 3'.

5 out-patient visits: Day 0 (blood sampling, vaccination), Day 1 (blood sampling), Day 3 (blood sampling), Day 7 (blood sampling), Day 28 (blood sampling)

Group Type PLACEBO_COMPARATOR

Placebo (Saline)

Intervention Type BIOLOGICAL

Randomised assignment

Interventions

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Boostrix

Randomised assignment

Intervention Type BIOLOGICAL

Placebo (Saline)

Randomised assignment

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Healthy male or female subjects aged 18-45 years (inclusive).
2. Male: Female ratio - 1:1.
3. Half of the subjects (n=120) will have received a previous Dt(pa) dose less than 5 years before, the other half (n=120) will have received a previous Dt(pa) dose 5 or more years before participating at this study.
4. The subject is, in the opinion of the investigator healthy based on medical history and clinical exam, with no active disease process that could interfere with the study endpoints.
5. Has a body Mass Index ≥18.0 and ≤30.0
6. Is able to read and understand the Informed Consent Form (ICF), and understand study procedures.
7. The subject has signed the ICF.
8. The subject is available for follow-up for the duration of the study.
9. The subject agrees to abstain from donating blood during their participation in the study, or longer if necessary.
10. If the subject is a heterosexually active female, she is willing to use an effective method of contraception with partner (oral contraceptive pill; intrauterine device; injectable or implanted contraceptive; condoms incorporating spermicide if using these; physiological or anatomical sterility) from 30 days prior to, and 3 months after, vaccination. Willing to undergo urine pregnancy tests prior to vaccination at screening.
11. The subject has venous access sufficient to allow blood sampling as per the protocol.

Exclusion Criteria

12. Pregnant or lactating at any point during the study from screening to final follow up.
13. Hypersensitivity to any component of the vaccine or subjects having shown signs of hypersensitivity after previous administration of diphtheria, tetanus, or pertussis vaccines.
14. Presence of primary or acquired immunodeficiency states with a total lymphocyte count less than 1,200 per mm3 or presenting other evidence of lack of cellular immune competence e.g. leukaemias, lymphomas, blood dyscrasias, or patients receiving immunosuppressive therapy (including regular use of oral or parenteral corticosteroids).
15. Use of any immune suppressing or immunomodulating drugs within 6 months of Visit 1.
16. Regular and prolonged use of non-steroidal anti-inflammatory drugs (oral or parenteral route) within 6 months of Visit 1 considered by the study physician as likely to interfere with immune responses.
17. Current intake of excessive amounts of alcohol and/or caffeine (as evaluated by the investigator) and not willing to adapt this use during the study period.
18. Currently performing extreme physical activities (as evaluated by the investigator) and not willing to adapt this use during the study period.
19. Receipt of a vaccine within 30 days prior to visit 1, or requirement to receive a vaccine within the 28 days following study vaccination, vaccination with a tetanus, diphtheria, pertussis combined vaccine within the last 6 months before the first study visit.
20. Presence of an acute severe febrile illness at time of immunisation.
21. History of alcohol, narcotic, benzodiazepine, rilatine, or other substance abuse or dependence within the 12 months preceding Visit 1.
22. Currently participating in another clinical study with an investigational or non-investigational drug or device, or has participated in a clinical trial within the 3 months preceding Visit 1.
23. Any condition that, in the investigator's opinion, compromises the subject's ability to meet protocol requirements or to complete the study.
24. Receipt of blood products or immunoglobulins, or blood donation within 3 months prior to visit 1.
25. Unable to read and speak Dutch or English to a fluency level adequate for the full comprehension of procedures required in participation and consent.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Surrey

OTHER

Sponsor Role collaborator

Novartis Vaccines

INDUSTRY

Sponsor Role collaborator

Max Planck Institute for Infection Biology

OTHER

Sponsor Role collaborator

deCODE genetics

INDUSTRY

Sponsor Role collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

Sanofi Pasteur, a Sanofi Company

INDUSTRY

Sponsor Role collaborator

Innovative Medicines Initiative

OTHER

Sponsor Role collaborator

University Hospital, Ghent

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Geert Leroux-Roels, Prof., MD

Role: PRINCIPAL_INVESTIGATOR

Center for Vaccinology

Locations

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Center for Vaccinology

Ghent, East-Flanders, Belgium

Site Status

Countries

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Belgium

Other Identifiers

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BioVacSafe - Boostrix

Identifier Type: -

Identifier Source: org_study_id