Study of BPZE1 (High Dose) Nasal Live Attenuated B. Pertussis Vaccine

NCT ID: NCT02453048

Last Updated: 2020-01-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-09-30

Study Completion Date

2017-12-31

Brief Summary

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This study evaluates the safety and immunogenicity of a higher dose formulation of a new live attenuated vaccine, BPZE1, intended to prevent Bordetella pertussis nasopharyngeal colonization and pertussis disease, and investigates whether higher doses of BPZE1 induce the live vaccine to colonize subjects' nasopharynx. The study is a Phase Ib (high dose), single centre, dose-escalating, placebo-controlled study of the live attenuated B. pertussis strain BPZE1 given as a single intranasal dose to healthy adult volunteer.

Detailed Description

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Conditions

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Pertussis Whooping Cough

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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BPZE1 - 10,000,000 cfu

Individuals will be vaccinated once intranasally with the designated dose of BPZE1 or Placebo at a Dose 2 x 0.4 mL (0.4 mL per nostril).

Group Type EXPERIMENTAL

BPZE1

Intervention Type BIOLOGICAL

Intranasal live, attenuated vaccine

Placebo

Intervention Type OTHER

Diluent

BPZE1 - 100,000,000 cfu

Individuals will be vaccinated once intranasally with the designated dose of BPZE1 or Placebo at a Dose 2 x 0.4 mL (0.4 mL per nostril).

Group Type EXPERIMENTAL

BPZE1

Intervention Type BIOLOGICAL

Intranasal live, attenuated vaccine

Placebo

Intervention Type OTHER

Diluent

BPZE1 - 1,000,000,000 cfu

Individuals will be vaccinated once intranasally with the designated dose of BPZE1 or Placebo at a Dose 2 x 0.4 mL (0.4 mL per nostril).

Group Type EXPERIMENTAL

BPZE1

Intervention Type BIOLOGICAL

Intranasal live, attenuated vaccine

Placebo

Intervention Type OTHER

Diluent

BPZE1 - High Antibody 1,000,000,000 cfu

Individuals will be vaccinated once intranasally with the designated dose of BPZE1 at a Dose 2 x 0.4 mL (0.4 mL per nostril).

Group Type EXPERIMENTAL

BPZE1

Intervention Type BIOLOGICAL

Intranasal live, attenuated vaccine

Interventions

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BPZE1

Intranasal live, attenuated vaccine

Intervention Type BIOLOGICAL

Placebo

Diluent

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Healthy individual between 18 and 32 years of age, vaccinated or unvaccinated with acellular pertussis vaccine.
2. Female subject of child bearing potential must be willing to ensure that they use a highly efficient method of contraception during the study (e.g. contraceptive pill, intrauterine contraceptive device).
3. Informed consent form (ICF) signed by the subject.
4. Subject shall be able to attend all scheduled visits and to understand and comply with the study procedures.

Exclusion Criteria

1. Individual with PT and/or PRN serum IgG antibodies ≥20 International units/ml (IU/ml). NOTE! One control group with PRN serum IgG antibodies ≥ 20 IU/ml will be included.
2. Vaccinated with the study vaccine in the Child Innovac study (EudraCT number 2010-019936-11).
3. Pregnant or lactating women. Pregnancy not planned and to be avoided during the study by use of effective contraceptive methods.
4. Blood pressure after resting ≥ 150/90 mm Hg at screening.
5. Heart rate after resting ≥ 80 bpm at screening.
6. Respiratory rate after resting ≥ 20/minute at screening.
7. Unwillingness to refrain from the use of nicotine products from screening through day 28.
8. Use of narcotic drugs and/or a history of drug/alcohol abuse with in the past 2 years prior to screening
9. The subject has donated blood or suffered from blood loss of at least 450 ml (1 unit of blood) within 60 days prior to screening or donated plasma within 14 days prior to screening.
10. Receipt of immunoglobulin, blood derived products, systemic corticosteroids or other immunosuppressant drugs within 90 days prior to day 0.
11. Asthma or other chronic respiratory problems.
12. Use of corticosteroids in the respiratory tract (e.g. nasal steroids, inhaled steroids) with in 30 days prior to day 0.
13. Receipt of a vaccine within the last 30 days prior to day 0 or planned vaccination with in the next 30 days after day 0.
14. Known hypersensitivity to any component of the study vaccine.
15. Current participation in any other clinical trial or participation (and during the whole study) in any clinical trial in the previous 3 months prior to day 0.
16. Inability to adhere to the protocol, including plans to move from the area.
17. Family (first degree) history of congenital or hereditary immunodeficiency.
18. Past or present infection with HIV, hepatitis B or C.
19. Chronic conditions requiring ongoing active medical interventions, such as diabetes mellitus or cardiovascular disease.
20. Any autoimmune or immunodeficiency disease/condition (inherited or iatrogenic).
21. Any medical condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives or might affect the safety of the individual, e.g. evolving encephalopathy not attributable to another identifiable cause within 7 days of administration of a previous dose of any vaccine, hospitalization due to major depression or history of suicidal attempt.
22. Abnormal laboratory values outside the limit of normal values for the screening laboratory with clinical significance at the discretion of the investigator.
23. Person in frequent contact with children less than 1 year of age (parent, childcare worker, nurse, etc) or residence in the same household as persons with known immunodeficiency including persons on immunosuppressant therapy.
Minimum Eligible Age

18 Years

Maximum Eligible Age

32 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nabil Al-Tawil, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska University Hospital

Locations

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Karolinska University Hospital

Huddinge, Stockholm County, Sweden

Site Status

Countries

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Sweden

References

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Thorstensson R, Trollfors B, Al-Tawil N, Jahnmatz M, Bergstrom J, Ljungman M, Torner A, Wehlin L, Van Broekhoven A, Bosman F, Debrie AS, Mielcarek N, Locht C. A phase I clinical study of a live attenuated Bordetella pertussis vaccine--BPZE1; a single centre, double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally to healthy adult male volunteers. PLoS One. 2014 Jan 8;9(1):e83449. doi: 10.1371/journal.pone.0083449. eCollection 2014.

Reference Type BACKGROUND
PMID: 24421886 (View on PubMed)

Jahnmatz M, Amu S, Ljungman M, Wehlin L, Chiodi F, Mielcarek N, Locht C, Thorstensson R. B-cell responses after intranasal vaccination with the novel attenuated Bordetella pertussis vaccine strain BPZE1 in a randomized phase I clinical trial. Vaccine. 2014 Jun 5;32(27):3350-6. doi: 10.1016/j.vaccine.2014.04.048. Epub 2014 Apr 29.

Reference Type BACKGROUND
PMID: 24793938 (View on PubMed)

Feunou PF, Kammoun H, Debrie AS, Locht C. Heterologous prime-boost immunization with live attenuated B. pertussis BPZE1 followed by acellular pertussis vaccine in mice. Vaccine. 2014 Jul 23;32(34):4281-8. doi: 10.1016/j.vaccine.2014.06.019. Epub 2014 Jun 17.

Reference Type BACKGROUND
PMID: 24950361 (View on PubMed)

Kammoun H, Feunou PF, Foligne B, Debrie AS, Raze D, Mielcarek N, Locht C. Dual mechanism of protection by live attenuated Bordetella pertussis BPZE1 against Bordetella bronchiseptica in mice. Vaccine. 2012 Aug 31;30(40):5864-70. doi: 10.1016/j.vaccine.2012.07.005. Epub 2012 Jul 17.

Reference Type BACKGROUND
PMID: 22814407 (View on PubMed)

Fedele G, Bianco M, Debrie AS, Locht C, Ausiello CM. Attenuated Bordetella pertussis vaccine candidate BPZE1 promotes human dendritic cell CCL21-induced migration and drives a Th1/Th17 response. J Immunol. 2011 May 1;186(9):5388-96. doi: 10.4049/jimmunol.1003765. Epub 2011 Mar 23.

Reference Type BACKGROUND
PMID: 21430219 (View on PubMed)

Skerry CM, Mahon BP. A live, attenuated Bordetella pertussis vaccine provides long-term protection against virulent challenge in a murine model. Clin Vaccine Immunol. 2011 Feb;18(2):187-93. doi: 10.1128/CVI.00371-10. Epub 2010 Dec 8.

Reference Type BACKGROUND
PMID: 21147936 (View on PubMed)

Feunou PF, Kammoun H, Debrie AS, Mielcarek N, Locht C. Long-term immunity against pertussis induced by a single nasal administration of live attenuated B. pertussis BPZE1. Vaccine. 2010 Oct 8;28(43):7047-53. doi: 10.1016/j.vaccine.2010.08.017. Epub 2010 Aug 13.

Reference Type BACKGROUND
PMID: 20708998 (View on PubMed)

Feunou PF, Bertout J, Locht C. T- and B-cell-mediated protection induced by novel, live attenuated pertussis vaccine in mice. Cross protection against parapertussis. PLoS One. 2010 Apr 15;5(4):e10178. doi: 10.1371/journal.pone.0010178.

Reference Type BACKGROUND
PMID: 20419113 (View on PubMed)

Mielcarek N, Debrie AS, Mahieux S, Locht C. Dose response of attenuated Bordetella pertussis BPZE1-induced protection in mice. Clin Vaccine Immunol. 2010 Mar;17(3):317-24. doi: 10.1128/CVI.00322-09. Epub 2010 Jan 27.

Reference Type BACKGROUND
PMID: 20107007 (View on PubMed)

Skerry CM, Cassidy JP, English K, Feunou-Feunou P, Locht C, Mahon BP. A live attenuated Bordetella pertussis candidate vaccine does not cause disseminating infection in gamma interferon receptor knockout mice. Clin Vaccine Immunol. 2009 Sep;16(9):1344-51. doi: 10.1128/CVI.00082-09. Epub 2009 Jul 22.

Reference Type BACKGROUND
PMID: 19625486 (View on PubMed)

Feunou PF, Ismaili J, Debrie AS, Huot L, Hot D, Raze D, Lemoine Y, Locht C. Genetic stability of the live attenuated Bordetella pertussis vaccine candidate BPZE1. Vaccine. 2008 Oct 23;26(45):5722-7. doi: 10.1016/j.vaccine.2008.08.018. Epub 2008 Aug 30.

Reference Type BACKGROUND
PMID: 18762220 (View on PubMed)

Jahnmatz M, Richert L, Al-Tawil N, Storsaeter J, Colin C, Bauduin C, Thalen M, Solovay K, Rubin K, Mielcarek N, Thorstensson R, Locht C; BPZE1 study team. Safety and immunogenicity of the live attenuated intranasal pertussis vaccine BPZE1: a phase 1b, double-blind, randomised, placebo-controlled dose-escalation study. Lancet Infect Dis. 2020 Nov;20(11):1290-1301. doi: 10.1016/S1473-3099(20)30274-7. Epub 2020 Jul 17.

Reference Type DERIVED
PMID: 32687804 (View on PubMed)

Lin A, Apostolovic D, Jahnmatz M, Liang F, Ols S, Tecleab T, Wu C, van Hage M, Solovay K, Rubin K, Locht C, Thorstensson R, Thalen M, Lore K. Live attenuated pertussis vaccine BPZE1 induces a broad antibody response in humans. J Clin Invest. 2020 May 1;130(5):2332-2346. doi: 10.1172/JCI135020.

Reference Type DERIVED
PMID: 31945015 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2015-001287-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C14-80

Identifier Type: -

Identifier Source: org_study_id

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