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

NCT02555540 | Completed Phase 4

• 1 other identifier: BioVacSafe - Boostrix
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prevention of Infections With Bordetella Pertussis

Outcome Measures

Primary Outcomes (28)

• Frequency of local vaccine-related clinical events

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

  At all timepoints from vaccination up to 28 days after vaccination

• Frequency of systemic vaccine-related clinical events.

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

  At all timepoints from vaccination up to 28 days after vaccination

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

  Up to 7 days after vaccination

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

  At all timepoints from vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in creatinin

  At all timepoints from vaccination up to 28 days after vaccination

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

  At all timepoints from vaccination up to 28 days after vaccination

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

  At all timepoints from vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in albumin

  At all timepoints from vaccination up to 28 days after vaccination

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

  At all timepoints from vaccination up to 28 days after vaccination

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

  At all timepoints from vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in total protein

  At all timepoints from vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in prothrombin/fibrinogen

  At all timepoints from vaccination up to 28 days after vaccination

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

  At selected timepoints from vaccination up to 28 days after vaccination

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

  At selected timepoints from vaccination up to 28 days after vaccination

• 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.

  At selected timepoints from vaccination up to 28 days after vaccination

• 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.

  At 7 days after vaccination

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

  At selected timepoints from vaccination up to 28 days after vaccination

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

  At selected timepoints from vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in haemoglobin

  At all timepoints from vaccination up to 28 days after vaccination

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

  At all timepoints from vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in haematocrit

  At all timepoints from vaccination up to 28 days after vaccination

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

  At all timepoints from vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in platelet count

  At all timepoints from vaccination up to 28 days after vaccination

• Change from pre-immunisation baseline values in white blood cells

  At all timepoints from vaccination up to 28 days after vaccination

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

  At all timepoints from vaccination up to 28 days after vaccination

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

  At all timepoints from vaccination up to 28 days after vaccination

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

  At all timepoints from vaccination up to 28 days after vaccination

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

  At all timepoints from vaccination up to 28 days after vaccination

Study Arms (16)

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

ACTIVE COMPARATOR

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)

Biological: Boostrix

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

ACTIVE COMPARATOR

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)

Biological: Boostrix

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

ACTIVE COMPARATOR

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)

Biological: Boostrix

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

ACTIVE COMPARATOR

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)

Biological: Boostrix

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

PLACEBO COMPARATOR

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)

Biological: Placebo (Saline)

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

PLACEBO COMPARATOR

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)

Biological: Placebo (Saline)

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

PLACEBO COMPARATOR

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)

Biological: Placebo (Saline)

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

PLACEBO COMPARATOR

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)

Biological: Placebo (Saline)

Boostrix, Male, <5 years, D2 visit

ACTIVE COMPARATOR

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)

Biological: Boostrix

Boostrix, Male, <5 years, D3 visit

ACTIVE COMPARATOR

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)

Biological: Boostrix

Boostrix, Female, <5 years, D2 visit

ACTIVE COMPARATOR

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)

Biological: Boostrix

Boostrix, Female, <5 years, D3 visit

ACTIVE COMPARATOR

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)

Biological: Boostrix

Placebo, Male, <5 years, D2 visit

PLACEBO COMPARATOR

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)

Biological: Placebo (Saline)

Placebo, Male, <5 years, D3 visit

PLACEBO COMPARATOR

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)

Biological: Placebo (Saline)

Placebo, Female, <5 years, D2 visit

PLACEBO COMPARATOR

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)

Biological: Placebo (Saline)

Placebo, Female, <5 years, D3 visit

PLACEBO COMPARATOR

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)

Biological: Placebo (Saline)

Interventions

Boostrix BIOLOGICAL

Randomised assignment

Boostrix, Female, <5 years, D2 visit; Boostrix, Female, <5 years, D3 visit; Boostrix, Female, >/= 5 years, D2 visit; Boostrix, Female, >/= 5 years, D3 visit; Boostrix, Male, <5 years, D2 visit; Boostrix, Male, <5 years, D3 visit; Boostrix, Male, >/= 5 years, D2 visit; Boostrix, Male, >/= 5 years, D3 visit

Placebo (Saline) BIOLOGICAL

Randomised assignment

Placebo, Female, <5 years, D2 visit; Placebo, Female, <5 years, D3 visit; Placebo, Female, >/= 5 years, D2 visit; Placebo, Female, >/= 5 years, D3 visit; Placebo, Male, <5 years, D2 visit; Placebo, Male, <5 years, D3 visit; Placebo, Male, >/= 5 years, D2 visit; Placebo, Male, >/= 5 years, D3 visit

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Center for Vaccinology

Ghent, East-Flanders, 9000, Belgium

Location

MeSH Terms

Interventions

Boostrix; Sodium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Geert Leroux-Roels, Prof., MD

  Center for Vaccinology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2015
• First Posted: September 21, 2015
• Study Start: August 24, 2015
• Primary Completion: December 15, 2015
• Study Completion: December 15, 2016
• Last Updated: December 20, 2022

Record last verified: 2022-12

Locations

BE (1)