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

NCT01188512 | Completed Phase 1 DMC

• 2 other identifiers: BT06-042010-019936-11
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pertussis

Keywords

Live nasal vaccine for prevention of pertussis

Outcome Measures

Primary Outcomes (1)

• General safety and local tolerability in the respiratory tract of a single ascending dose of the genetically modified B. pertussis strain

  To determine * general safety, i. e. general well-being of the volunteers and any symptoms felt by the volunteers with onset within one month after vaccine administration. * vital signs: Blood pressure, heart rate, respiratory rate, oral temperature. * abnormalities in the following laboratory data: Haemoglobin, total and differential white blood cell count, platelets (thrombocytes). * specific side effects: Local symptoms from the respiratory tract: Sneezing, swollen nose, cough, bleeding from the nose, pain or other symptoms from the ear, symptoms from the eyes (redness, secretion).

  6 months

Secondary Outcomes (2)

• Attachment of the BPZE1 strain to the nasopharyngeal mucosa

  Up to 50 days after vaccination

• Immunogenicity

  6 months

Study Arms (4)

BPZE1 - Low dose

EXPERIMENTAL

1,000 colony forming units (cfu) of BPZE1

Biological: BPZE1

BPZE1- middle dose

EXPERIMENTAL

100,000 colony forming units (cfu) of BPZE1

Biological: BPZE1

BPZE1 - High dose

EXPERIMENTAL

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

Biological: BPZE1

Placebo

PLACEBO COMPARATOR

Formulation buffer

Biological: Placebo

Interventions

BPZE1 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; BPZE1 - Low dose; BPZE1- middle dose

Placebo BIOLOGICAL

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

Placebo

Eligibility Criteria

• Age: 19 Years - 31 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• European Union: collaborator
• Swedish Institute for Infectious Disease Control: collaborator
• Innogenetics: collaborator

Study Sites (1)

Karolinska University Hospital

Solna, 171 76, Sweden

Location

Related Publications (8)

• 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.

  PMID: 16839199 BACKGROUND

• 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.

  PMID: 18762220 BACKGROUND

• 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.

  PMID: 20107007 BACKGROUND

• 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.

  PMID: 20184606 BACKGROUND

• 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.

  PMID: 19625486 BACKGROUND

• 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.

  PMID: 24421886 RESULT

• 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.

  PMID: 24793938 RESULT

• 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.

  PMID: 24261996 DERIVED

MeSH Terms

Conditions

Whooping Cough

Condition Hierarchy (Ancestors)

Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Respiratory Tract Diseases

Study Officials

• Camille Locht, PhD

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

  STUDY DIRECTOR

• Nabil Al-Tawil, MD, PhD

  Karolinska Trial Alliance

  PRINCIPAL INVESTIGATOR

• Rigmor Thorstensson, PhD

  Swedish Institute for Infectious Disease Control

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2010
• First Posted: August 25, 2010
• Study Start: August 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: January 1, 2012
• Last Updated: December 10, 2025

Record last verified: 2012-01

Locations

SE (1)