First Adult Safety Trial on Nasal Live Attenuated B. Pertussis Vaccine

NCT ID: NCT01188512

Last Updated: 2012-01-31

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

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-08-31

Study Completion Date

2012-01-31

Brief Summary

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The purpose of this study is to evaluate the safety and immunogenicity of a new live attenuated vaccine against whooping-cough. It is a phase1, single centre, dose-escalating, placebo-controlled study on a genetically modified B. pertussis strain given as a single intranasal dose to healthy adult male volunteers.

Effective vaccines are needed to protect young infants (from 0 to 6 months, today the most vulnerable age group), preferably after a single administration very early in life. The successful outcome of this project would constitute an important milestone towards nasal vaccination of infants, possibly at birth with a novel, single-dose pertussis vaccine. Our ultimate aim is to protect infants in the most vulnerable age group, before the regular vaccination schedule using already available vaccines is applied. The ultimate aim is thus not to replace current vaccination schedules with available vaccines, but to add a first nasal vaccination to protect very early in life.

Detailed Description

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Conditions

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Pertussis

Keywords

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Live nasal vaccine for prevention of pertussis

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 - Low dose

1,000 colony forming units (cfu) of BPZE1

Group Type EXPERIMENTAL

BPZE1

Intervention Type BIOLOGICAL

Individuals will be vaccinated once intranasally with the designated dose of BPZE1 Dose 2 x 0.1 mL (0.1 mL per nostril).

BPZE1- middle dose

100,000 colony forming units (cfu) of BPZE1

Group Type EXPERIMENTAL

BPZE1

Intervention Type BIOLOGICAL

Individuals will be vaccinated once intranasally with the designated dose of BPZE1 Dose 2 x 0.1 mL (0.1 mL per nostril).

BPZE1 - High dose

10,000,000 colony forming units (cfu) of BPZE1

Group Type EXPERIMENTAL

BPZE1

Intervention Type BIOLOGICAL

Individuals will be vaccinated once intranasally with the designated dose of BPZE1 Dose 2 x 0.1 mL (0.1 mL per nostril).

Placebo

Formulation buffer

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

Individuals will get placebo once intranasally. Dose 2 x 0.1 mL (0.1 mL per nostril).

Interventions

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BPZE1

Individuals will be vaccinated once intranasally with the designated dose of BPZE1 Dose 2 x 0.1 mL (0.1 mL per nostril).

Intervention Type BIOLOGICAL

Placebo

Individuals will get placebo once intranasally. Dose 2 x 0.1 mL (0.1 mL per nostril).

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

Subject will be included in the study if he meets all the following criteria:

* Healthy male born between 1979 and 1991 who has not experienced clinical pertussis (lab. Verified) during the past 10 years and who has not been vaccinated with any pertussis vaccine.
* Informed consent form signed by the subject.
* Subject shall be able to attend all scheduled visits and to understand and comply with the study procedures (e.g. able to read and write Swedish).

Exclusion Criteria

If any of the following criteria are met, the subject must not be included in the study:

* Individuals with pertussis toxin serum IgG antibodies ≥20 units/mL.
* Blood pressure after resting ≥ 150/90 mmHg.
* Heart rate after resting ≥80 bpm.
* Respiratory rate after resting ≥ 20/minute.
* Unwillingness to refrain from the use of nicotine products from screening through day 28.
* Use of narcotic drugs/alcohol and/or a history of previous use of drug/alcohol abuse whitin the past 2 years prior to screening
* 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.
* Receipt of immunoglobulin, blood derived products, systemic corticosteroids or other immunosuppressant drugs within 90 days prior to day 0.
* Use of corticosteroids in the respiratory tract(e.g. nasal steroids, inhaled steroids) whitin 30 days prior to day 0.
* Use of herbal medications or dietary supplements within 7 days prior to day 0 at the discretion of the investigator. Unwillingness to refrain from herbal medications or dietary supplements within 30 days after day 0 at the discretion of the investigator.
* Receipt of a vaccine within the last 30 days prior to day 0 or planned vaccination within the next 30 days after day 0.
* Evolving encephalopathy not attributable to another identifiable cause within 7 days of administration of a previous dose of any vaccine.
* Known hypersensitivity to any component of the study vaccine.
* 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.
* Inability to adhere to the protocol, including plans to move from the area.
* Family history of congenital or hereditary immunodeficiency (first degree).
* Infection with HIV, hepatitis B or C.
* Any medical condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
* Clinically significant abnormal laboratory values at the discretion of the investigator.
* Person in frequent contact with children less than 1 year of age (father, childcare worker, nurse, etc…) or residence in the same household as persons with known immunodeficiency.
Minimum Eligible Age

19 Years

Maximum Eligible Age

31 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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European Union

OTHER

Sponsor Role collaborator

Swedish Institute for Infectious Disease Control

OTHER

Sponsor Role collaborator

Innogenetics

UNKNOWN

Sponsor Role collaborator

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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Camille Locht, PhD

Role: STUDY_DIRECTOR

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

Nabil Al-Tawil, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Trial Alliance

Rigmor Thorstensson, PhD

Role: PRINCIPAL_INVESTIGATOR

Swedish Institute for Infectious Disease Control

Locations

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Karolinska University Hospital

Solna, , Sweden

Site Status

Countries

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Sweden

References

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Mielcarek N, Debrie AS, Raze D, Bertout J, Rouanet C, Younes AB, Creusy C, Engle J, Goldman WE, Locht C. Live attenuated B. pertussis as a single-dose nasal vaccine against whooping cough. PLoS Pathog. 2006 Jul;2(7):e65. doi: 10.1371/journal.ppat.0020065.

Reference Type BACKGROUND
PMID: 16839199 (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)

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)

Kavanagh H, Noone C, Cahill E, English K, Locht C, Mahon BP. Attenuated Bordetella pertussis vaccine strain BPZE1 modulates allergen-induced immunity and prevents allergic pulmonary pathology in a murine model. Clin Exp Allergy. 2010 Jun;40(6):933-41. doi: 10.1111/j.1365-2222.2010.03459.x. Epub 2010 Feb 22.

Reference Type BACKGROUND
PMID: 20184606 (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)

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 DERIVED
PMID: 24793938 (View on PubMed)

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 DERIVED
PMID: 24421886 (View on PubMed)

Schnoeller C, Roux X, Sawant D, Raze D, Olszewska W, Locht C, Openshaw PJ. Attenuated Bordetella pertussis vaccine protects against respiratory syncytial virus disease via an IL-17-dependent mechanism. Am J Respir Crit Care Med. 2014 Jan 15;189(2):194-202. doi: 10.1164/rccm.201307-1227OC.

Reference Type DERIVED
PMID: 24261996 (View on PubMed)

Other Identifiers

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2010-019936-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BT06-04

Identifier Type: -

Identifier Source: org_study_id