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

NCT02453048 | Completed Phase 1 Results DMC

• 2 other identifiers: C14-802015-001287-20
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pertussis; Whooping Cough

Keywords

Pertussis; Colonization; Vaccine; Immune response; BPZE1; Infection; Bordetella pertussis; B. pertussis; respiratory Tract Infection

Outcome Measures

Primary Outcomes (1)

• The Primary Safety Endpoint is the Number and Percentage of Participants Per Dose Group and Randomized Allocation, With at Least One of the Following Adverse Events Between Day 0 and Day 28

  Percentage is based on subjects experiencing at least one of the following events: * Cough and spasmodic cough of grade 2 or higher * Other respiratory tract AE related or possibly related to vaccination of grade 3 or higher * Any other AE related or possibly related to vaccination of grade 3 or higher

  28 days

Secondary Outcomes (2)

• Proportion of Subjects With BPZE1 Colonization

  28 days

• The Proportion of Subjects That Have an Antibody Response to BPZE1 Vaccination

  6 months

Study Arms (4)

BPZE1 - 10,000,000 cfu

EXPERIMENTAL

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).

Biological: BPZE1; Other: Placebo

BPZE1 - 100,000,000 cfu

EXPERIMENTAL

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).

BPZE1 - 1,000,000,000 cfu

EXPERIMENTAL

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).

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

EXPERIMENTAL

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).

Interventions

BPZE1 BIOLOGICAL

Intranasal live, attenuated vaccine

BPZE1 - 10,000,000 cfu

Placebo OTHER

Diluent

BPZE1 - 10,000,000 cfu

Eligibility Criteria

• Age: 18 Years - 32 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy individual between 18 and 32 years of age, vaccinated or unvaccinated with acellular pertussis vaccine.
• 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).
• Informed consent form (ICF) signed by the subject.
• Subject shall be able to attend all scheduled visits and to understand and comply with the study procedures.

You may not qualify if:

• 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.
• Vaccinated with the study vaccine in the Child Innovac study (EudraCT number 2010-019936-11).
• Pregnant or lactating women. Pregnancy not planned and to be avoided during the study by use of effective contraceptive methods.
• Blood pressure after resting ≥ 150/90 mm Hg at screening.
• Heart rate after resting ≥ 80 bpm at screening.
• Respiratory rate after resting ≥ 20/minute at screening.
• Unwillingness to refrain from the use of nicotine products from screening through day 28.
• Use of narcotic drugs and/or a history of drug/alcohol abuse with in 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.
• Asthma or other chronic respiratory problems.
• Use of corticosteroids in the respiratory tract (e.g. nasal steroids, inhaled steroids) with in 30 days prior to day 0.
• 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.
• 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

Study Sites (1)

Karolinska University Hospital

Huddinge, Stockholm County, 141 86, Sweden

Location

Related Publications (13)

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 24950361 BACKGROUND

• 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.

  PMID: 22814407 BACKGROUND

• 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.

  PMID: 21430219 BACKGROUND

• 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.

  PMID: 21147936 BACKGROUND

• 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.

  PMID: 20708998 BACKGROUND

• 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.

  PMID: 20419113 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

• 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

• 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

• 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.

  PMID: 32687804 RESULT

• 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.

  PMID: 31945015 DERIVED

MeSH Terms

Conditions

Whooping Cough; Infections; Respiratory Tract Infections

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Ken Solovay
• Organization: ILIAD Biotechnologies

ken@iliadbio.com

9543360777

Study Officials

• Nabil Al-Tawil, MD, PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: May 18, 2015
• First Posted: May 25, 2015
• Study Start: September 1, 2015
• Primary Completion: March 1, 2017
• Study Completion: December 1, 2017
• Last Updated: February 27, 2026
• Results First Posted: January 2, 2020

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)