PertussisPhase 1NCT02453048
Study of BPZE1 (High Dose) Nasal Live Attenuated B. Pertussis Vaccine
A Phase 1 study testing BPZE1 in people with Pertussis and Whooping Cough, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 32 yearsHealthy volunteers can take part
- Conditions the study is for
- Pertussis, Whooping Cough
- What is being tested?
- BPZE1
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteSweden
- Study dates
- Sep 2015to Dec 2017
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 32 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- Inability to adhere to the protocol, including plans to move from the area.
- Family (first degree) history of congenital or hereditary immunodeficiency.
- Past or present infection with HIV, hepatitis B or C.
- Chronic conditions requiring ongoing active medical interventions, such as diabetes mellitus or cardiovascular disease.
- Any autoimmune or immunodeficiency disease/condition (inherited or iatrogenic).
- 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.
- Abnormal laboratory values outside the limit of normal values for the screening laboratory with clinical significance at the discretion of the investigator.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase Ib (High Dose), Single Centre, Dose-escalating, Placebo-controlled, Randomized Study of a Live Attenuated B. Pertussis Strain Given as a Single Intranasal Dose to Healthy Adult Volunteers
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
- Being tested
- BPZE1, Placebo
- Keywords
- Pertussis, Colonization, Vaccine, Immune response, BPZE1, Infection, Bordetella pertussis, B. pertussis, respiratory Tract Infection
- Medical subject headings
- Whooping Cough, Infections, Respiratory Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BPZE1Biological
Intranasal live, attenuated vaccine
PlaceboOther
Diluent
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 28 days
Secondary outcomes (2)
Proportion of Subjects With BPZE1 Colonization
To assess the proportion of subjects having positive colonization of the human respiratory tract by live attenuated B. pertussis strain BPZE1 per group at any time period measured at 4, 7, 11, 14, 21 and 28 days post vaccination.
Measured: 28 days
The Proportion of Subjects That Have an Antibody Response to BPZE1 Vaccination
To assess the number of immune responders and levels of Immunoglobulin G/Immunoglobulin A (IgG/IgA) antibodies to pertussis toxin (PT), filamentous haemagglutinin adhesin (FHA), Pertactin (PRN), and fimbriae 2/3 in serum and nasopharyngeal aspirate.
A positive antibody response after vaccination is defined as at least 100% increase from pre- to post-vaccination, to at least 4 times minimum level of detection (MLD) for PT, FHA, PRN, and fimbriae 2/3 in the post-vaccination sample. The 4 antigens described are the standard 4 antigens historically used to describe a serum immunological response to B. pertussis. The absolute serum antibody titers have not shown a correlation of protection in previous pertussis vaccine studies of the current acellular vaccine and there is no known serum antigen threshold of protection for pertussis.
Antibodies are measured before vaccination and at 4, 7, 11, 14, 21, 28 days, 6-months and 12-months post-vaccination.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2015 (estimated)
- Study startSep 2015
- Primary completionMar 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for PertussisStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Nabil Al-Tawil, MD, PhD, Principal investigator, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02453048
- Sponsor's protocol ID
- C14-80
- Other IDs
- 2015-001287-20, 2015
- Status last verified
- Jan 2018
- First submitted
- 18 May 2015
- Last updated
- 27 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 24421886Jahnmatz 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.
PubMed 24793938Feunou 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.
PubMed 24950361Kammoun 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.
PubMed 22814407Fedele 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.
PubMed 21430219Skerry 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.
PubMed 21147936Feunou 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.
PubMed 20708998Feunou 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.
PubMed 20419113Mielcarek 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.
PubMed 20107007Skerry 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.
PubMed 19625486Feunou 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.
PubMed 18762220Jahnmatz 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.
PubMed 32687804Lin 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.
PubMed 31945015