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

Pertussis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02453048
• Other study ID #: C14-80
• Secondary ID: 2015-001287-20
• Status: Completed
• Phase: Phase 1
• Start date: September 2015
• Est. completion date: December 2017

Study information

• Verified date: January 2018
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: December 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 32 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pertussis
• Whooping Cough

Intervention

Biological:
• BPZE1
Intranasal live, attenuated vaccine

Other:
• Placebo
Diluent

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital	Huddinge	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

Sweden, 

References & Publications (11)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Thorstensson R, Trollfors B, Al-Tawil N, Jahnmatz M, Bergström J, Ljungman M, Törner 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	28 days
Secondary	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.	6 months