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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-001287-20 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BPZE1 | Biological | Intranasal live, attenuated vaccine |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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:
| 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| The Proportion of Subjects That Have an Antibody Response to BPZE1 Vaccination |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nabil Al-Tawil, MD, PhD | Karolinska University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karolinska University Hospital | Huddinge | Stockholm County | 141 86 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24421886 | 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. | |
| 24793938 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Individuals will be vaccinated once intranasally with the designated dose of Placebo at a Dose 2 x 0.4 mL (0.4 mL per nostril). Placebo: Diluent |
| FG001 | BPZE1 - 10,000,000 Cfu | 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). BPZE1: Intranasal live, attenuated vaccine |
| FG002 | BPZE1 - 100,000,000 Cfu | 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). BPZE1: Intranasal live, attenuated vaccine |
| FG003 | BPZE1 - 1,000,000,000 Cfu | 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). BPZE1: Intranasal live, attenuated vaccine |
| FG004 | BPZE1 - High Antibody 1,000,000,000 Cfu | Individuals with high baseline antibodies will be vaccinated once intranasally with the designated dose of BPZE1 at a Dose 2 x 0.4 mL (0.4 mL per nostril). BPZE1: Intranasal live, attenuated vaccine |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Individuals will be vaccinated once intranasally with the designated dose of Placebo at a Dose 2 x 0.4 mL (0.4 mL per nostril). Placebo: Diluent |
| BG001 | BPZE1 - 10,000,000 Cfu |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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:
| Arms (Placebo separated from randomized groups) | Posted | Count of Participants | Participants | 28 days |
|
14 days, 1 month, 3 months, 6 months, 1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Subjects receiving intranasal Placebo | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough - week 1 | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ken Solovay | ILIAD Biotechnologies | 9543360777 | ken@iliadbio.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 9, 2016 | Oct 17, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D014917 | Whooping Cough |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| ID | Term |
|---|---|
| D001885 | Bordetella Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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| Placebo |
| Other |
Diluent |
|
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 |
| 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. |
| 24950361 | 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. |
| 22814407 | 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. |
| 21430219 | 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. |
| 21147936 | 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. |
| 20708998 | 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. |
| 20419113 | 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. |
| 20107007 | 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. |
| 19625486 | 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. |
| 18762220 | 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. |
| 32687804 | Result | 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. |
| 31945015 | Derived | 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. |
| Lost to Follow-up |
|
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).
BPZE1: Intranasal live, attenuated vaccine
| BG002 | BPZE1 - 100,000,000 Cfu | 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). BPZE1: Intranasal live, attenuated vaccine |
| BG003 | BPZE1 - 1,000,000,000 Cfu | 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). BPZE1: Intranasal live, attenuated vaccine |
| BG004 | BPZE1 - High Antibody 1,000,000,000 Cfu | Individuals with high baseline antibodies will be vaccinated once intranasally with the designated dose of BPZE1 at a Dose 2 x 0.4 mL (0.4 mL per nostril). BPZE1: Intranasal live, attenuated vaccine |
| BG005 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Height | Median | Inter-Quartile Range | m |
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| BMI | Median | Inter-Quartile Range | kg/m^2 |
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| Weight | Median | Inter-Quartile Range | kg |
|
| Oral Temperature | Median | Inter-Quartile Range | C |
|
Subjects receiving 10^7 CFU of intranasal BPZE1
| OG002 | Medium Dose Group | Subjects receiving 10^8 CFU of intranasal BPZE1 |
| OG003 | High Dose Group | Subjects receiving 10^9 CFU of intranasal BPZE1 |
| OG004 | PRN High Group | Subjects with a pre-existing baseline PRN > 20 IU that received 10^9 CFU of intranasal BPZE1 (non-randomized group) |
|
|
| 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. | Posted | Count of Participants | Participants | 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. | Posted | Count of Participants | Participants | 6 months |
|
|
|
| 12 |
| 0 |
| 12 |
| 11 |
| 12 |
| EG001 | Low Dose Group | Subjects receiving 10^7 CFU of intranasal BPZE1 | 0 | 12 | 1 | 12 | 11 | 12 |
| EG002 | Medium Dose Group | Subjects receiving 10^8 CFU of intranasal BPZE1 | 0 | 12 | 1 | 12 | 11 | 12 |
| EG003 | High Dose Group | Subjects receiving 10^9 CFU of intranasal BPZE1 | 0 | 12 | 0 | 12 | 9 | 12 |
| EG004 | PRN High Group | Subjects with a pre-existing baseline PRN > 20 IU that received 10^9 CFU of intranasal BPZE1 (non-randomized group) | 0 | 6 | 0 | 6 | 5 | 6 |
| Renal Failure Acute | Renal and urinary disorders | Non-systematic Assessment |
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| Cough - week 2 | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Fatigue - week 1 | General disorders | Systematic Assessment |
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| Fatigue - Week 2 | General disorders | Systematic Assessment |
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| Headache - week 1 | Nervous system disorders | Systematic Assessment |
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| Headache - week 2 | Nervous system disorders | Systematic Assessment |
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| Nasal Congestion - week 1 | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Nasal Congestion - week 2 | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Rhinorrhoea - week 1 | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Rhinorrhoea - week 2 | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Sneezing - week 1 | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Sneezing - week 2 | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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Publications will be co-authored by the PI and the Sponsor (Inserm).
| D012140 | Respiratory Tract Diseases |
| Not Colonized |
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| 1 Antigen |
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| 2 Antigens |
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| 3 Antigens |
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| 4 Antigens |
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| IgA Response |
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| IgG or IgA Response |
|