Clinical trial NCT02453048: Study of BPZE1 (High Dose) Nasal Live Attenuated B. Pertussis Vaccine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pertussis
Whooping Cough
Keywords: Pertussis
Colonization
Vaccine
Immune response
BPZE1
Infection
Bordetella pertussis
B. pertussis
respiratory Tract Infection
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2015-05-25
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 32
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 28 days
Secondary outcomes:
measure: Proportion of Subjects With BPZE1 Colonization
timeFrame: 28 days
measure: The Proportion of Subjects That Have an Antibody Response to BPZE1 Vaccination
timeFrame: 6 months
Other outcomes:
Locations:
city: Huddinge
country: Sweden
facility: Karolinska University Hospital
state: Stockholm
Study officials:
affiliation: Karolinska University Hospital
name: Nabil Al-Tawil, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.