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Completed

NCT Number: NCT02555540

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

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.

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Key information

Conditions

Prevention of Infections With Bordetella Pertussis

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Center for Vaccinology

Ghent, East-Flanders, 9000, Belgium

About this study

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:

  • 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.
  • 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).
  • Genetic testing of subjects when deemed necessary (genetic testing analysis may be SNP (single nucleotide polymorphism) analysis or full genome analysis).
  • 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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy male or female subjects aged 18-45 years (inclusive).
  • Male: Female ratio - 1:1.
  • 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.
  • 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.
  • Has a body Mass Index ≥18.0 and ≤30.0
  • Is able to read and understand the Informed Consent Form (ICF), and understand study procedures.
  • The subject has signed the ICF.
  • The subject is available for follow-up for the duration of the study.
  • The subject agrees to abstain from donating blood during their participation in the study, or longer if necessary.
  • 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.
  • The subject has venous access sufficient to allow blood sampling as per the protocol.

Exclusion criteria

  • Pregnant or lactating at any point during the study from screening to final follow up.
  • Hypersensitivity to any component of the vaccine or subjects having shown signs of hypersensitivity after previous administration of diphtheria, tetanus, or pertussis vaccines.
  • 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).
  • Use of any immune suppressing or immunomodulating drugs within 6 months of Visit 1.
  • 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.
  • 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.
  • Currently performing extreme physical activities (as evaluated by the investigator) and not willing to adapt this use during the study period.
  • 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.
  • Presence of an acute severe febrile illness at time of immunisation.
  • History of alcohol, narcotic, benzodiazepine, rilatine, or other substance abuse or dependence within the 12 months preceding Visit 1.
  • 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.
  • Any condition that, in the investigator's opinion, compromises the subject's ability to meet protocol requirements or to complete the study.
  • Receipt of blood products or immunoglobulins, or blood donation within 3 months prior to visit 1.
  • Unable to read and speak Dutch or English to a fluency level adequate for the full comprehension of procedures required in participation and consent.

Treatment and study plan

Boostrix

Biological

Randomised assignment

Placebo (Saline)

Biological

Randomised assignment

Primary outcomes

  1. Frequency of local vaccine-related clinical events

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

    Participants will report these events on a diary, measuring local events or scoring them from 0 (absent) to 3 (severe)

  2. Frequency of systemic vaccine-related clinical events.

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

    Participants will report these events on a diary, scoring them from 0 (absent) to 3 (severe)

  3. Physiological assessments: Change from pre-immunisation baseline values in body temperature.

    Time frame: Up to 7 days after vaccination

  4. Change from pre-immunisation baseline values in 'Erythrocyte Sedimentation Rate' (ESR)

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  5. Change from pre-immunisation baseline values in creatinin

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  6. Change from pre-immunisation baseline values in C Reactive Protein (CRP)

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  7. Change from pre-immunisation baseline values in aspartate transaminase (AST)/ alanine transaminase (ALT)

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  8. Change from pre-immunisation baseline values in albumin

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  9. Change from pre-immunisation baseline values in estimated glomerular filtration rate (eGFR)

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  10. Change from pre-immunisation baseline values in gamma glutamyl transpeptidase (GGT)

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  11. Change from pre-immunisation baseline values in total protein

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  12. Change from pre-immunisation baseline values in prothrombin/fibrinogen

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  13. Change from pre-immunisation baseline values in global gene expression measured on whole blood samples.

    Time frame: At selected timepoints from vaccination up to 28 days after vaccination

  14. Change from pre-immunisation baseline values in metabolic gene expression measured on whole blood samples.

    Time frame: At selected timepoints from vaccination up to 28 days after vaccination

  15. Change from pre-immunisation baseline values in serum levels of antibodies to vaccine antigens (anti-T, anti-D, anti-PT, anti-FHA and anti-PRN) in serum samples.

    Time frame: At selected timepoints from vaccination up to 28 days after vaccination

  16. Change from pre-immunisation values of adaptive cellular immune response via enumeration of TT-, DT-, PT-, FHA- and PTN-specific CD3/CD4+ or CD3/CD8+ T cells expressing activation markers/cytokines following IV stimulation and analysis by flow cytometry.

    Time frame: At 7 days after vaccination

  17. Change from pre-immunisation baseline values in concentration of selected cytokines and acute phase proteins in serum samples

    Time frame: At selected timepoints from vaccination up to 28 days after vaccination

  18. Change from pre-immunisation baseline values in pathway activation measured on whole blood samples.

    Time frame: At selected timepoints from vaccination up to 28 days after vaccination

  19. Change from pre-immunisation baseline values in haemoglobin

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  20. Change from pre-immunisation baseline values in red blood cell count

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  21. Change from pre-immunisation baseline values in haematocrit

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  22. Change from pre-immunisation baseline values in white blood cell count

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  23. Change from pre-immunisation baseline values in platelet count

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  24. Change from pre-immunisation baseline values in white blood cells

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  25. Change from pre-immunisation baseline values in 'mean corpuscular volume'

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  26. Change from pre-immunisation baseline values in 'mean corpuscular heamoglobin'

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  27. Change from pre-immunisation baseline values in 'mean corpuscular heamoglobin concentration'

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

  28. Change from pre-immunisation baseline values in Cell Mediated Immunity status in response to in vitro antigen stimulation

    Time frame: At all timepoints from vaccination up to 28 days after vaccination

Sponsors and collaborators

Lead sponsor

University Hospital, Ghent

Other

Collaborators

  • GlaxoSmithKline
  • Innovative Medicines Initiative
  • Max Planck Institute for Infection Biology
  • Novartis Vaccines
  • Sanofi Pasteur, a Sanofi Company
  • University of Surrey
  • deCODE genetics

Registry information

Official study title

Clinical Study to Generate a Set of Data Characterising Clinical Events, Physiological Responses, and Innate and Adaptive Immune Responses Following a Single IM Immunisation With Boostrix® or Placebo in Healthy Adults

Important dates

Study start
2015
Primary completion
2015
Study completion
2016
First posted
Sep 21, 2015
Registry last updated
Dec 20, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.