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

Sponsor
Institut National de la Santé Et de la Recherche Médicale, France (Other)
Overall Status
Completed
CT.gov ID
NCT02453048
Collaborator
(none)
54
Enrollment
1
Location
4
Arms
27
Duration (Months)
2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: BPZE1
  • Other: Placebo
 Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
54 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
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 Start Date :
Sep 1, 2015
Actual Primary Completion Date :
Mar 1, 2017
Actual Study Completion Date :
Dec 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: BPZE1 - 10,000,000 cfu

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
Intranasal live, attenuated vaccine

Other: Placebo
Diluent
Experimental: BPZE1 - 100,000,000 cfu

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
Intranasal live, attenuated vaccine

Other: Placebo
Diluent
Experimental: BPZE1 - 1,000,000,000 cfu

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
Intranasal live, attenuated vaccine

Other: Placebo
Diluent
Experimental: BPZE1 - High Antibody 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).

Biological: BPZE1
Intranasal live, attenuated vaccine

Outcome Measures

Primary Outcome Measures

  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 [28 days]

    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

Secondary Outcome Measures

  1. Proportion of Subjects With BPZE1 Colonization [28 days]

    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.

  2. The Proportion of Subjects That Have an Antibody Response to BPZE1 Vaccination [6 months]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 32 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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

  9. Use of narcotic drugs and/or a history of drug/alcohol abuse with in the past 2 years prior to screening

  10. 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.

  11. Receipt of immunoglobulin, blood derived products, systemic corticosteroids or other immunosuppressant drugs within 90 days prior to day 0.

  12. Asthma or other chronic respiratory problems.

  13. Use of corticosteroids in the respiratory tract (e.g. nasal steroids, inhaled steroids) with in 30 days prior to day 0.

  14. 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.

  15. Known hypersensitivity to any component of the study vaccine.

  16. 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.

  17. Inability to adhere to the protocol, including plans to move from the area.

  18. Family (first degree) history of congenital or hereditary immunodeficiency.

  19. Past or present infection with HIV, hepatitis B or C.

  20. Chronic conditions requiring ongoing active medical interventions, such as diabetes mellitus or cardiovascular disease.

  21. Any autoimmune or immunodeficiency disease/condition (inherited or iatrogenic).

  22. 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.

  23. Abnormal laboratory values outside the limit of normal values for the screening laboratory with clinical significance at the discretion of the investigator.

  24. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Karolinska University Hospital Huddinge Stockholm Sweden 141 86

Sponsors and Collaborators

  • Institut National de la Santé Et de la Recherche Médicale, France

Investigators

  • Principal Investigator: Nabil Al-Tawil, MD, PhD, Karolinska University Hospital

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier:
NCT02453048
Other Study ID Numbers:
  • C14-80
  • 2015-001287-20
First Posted:
May 25, 2015
Last Update Posted:
Jan 2, 2020
Last Verified:
Jan 1, 2018
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France
Pertussis
Colonization
Vaccine
Immune response
BPZE1
Infection
Bordetella pertussis
B. pertussis
respiratory Tract Infection
Additional relevant MeSH terms:
Whooping Cough

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Placebo BPZE1 - 10,000,000 Cfu BPZE1 - 100,000,000 Cfu BPZE1 - 1,000,000,000 Cfu BPZE1 - High Antibody 1,000,000,000 Cfu
Arm/Group Description 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 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 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 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 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
Period Title: Overall Study
STARTED 12 12 12 12 6
6-month Follow-up 12 12 12 12 6
COMPLETED 12 11 10 12 0
NOT COMPLETED 0 1 2 0 6

Baseline Characteristics

Arm/Group Title Placebo BPZE1 - 10,000,000 Cfu BPZE1 - 100,000,000 Cfu BPZE1 - 1,000,000,000 Cfu BPZE1 - High Antibody 1,000,000,000 Cfu Total
Arm/Group Description 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 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 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 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 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 Total of all reporting groups
Overall Participants 12 12 12 12 6 54
Age, Customized (Count of Participants)
<20 years
2
16.7%
0
0%
0
0%
0
0%
0
0%
2
3.7%
20-25 years
3
25%
2
16.7%
4
33.3%
3
25%
2
33.3%
14
25.9%
25-30 years
7
58.3%
7
58.3%
7
58.3%
6
50%
4
66.7%
31
57.4%
>=30 years
0
0%
3
25%
1
8.3%
3
25%
0
0%
7
13%
Sex: Female, Male (Count of Participants)
Female
6
50%
5
41.7%
2
16.7%
7
58.3%
1
16.7%
21
38.9%
Male
6
50%
7
58.3%
10
83.3%
5
41.7%
5
83.3%
33
61.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Not Hispanic or Latino
12
100%
12
100%
12
100%
12
100%
6
100%
54
100%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Region of Enrollment (participants) [Number]
Sweden
12
100%
12
100%
12
100%
12
100%
6
100%
54
100%
Height (m) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [m]
1.74
1.77
1.8
1.72
1.76
1.76
BMI (kg/m^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m^2]
22
22
22
23
22
22
Weight (kg) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg]
69
71
74
69
69
70
Oral Temperature (C) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [C]
36.5
36.8
36.6
36.6
36.3
36.6

Outcome Measures

1. Primary Outcome
Title 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
Description 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
Time Frame 28 days

Outcome Measure Data

Analysis Population Description
Arms (Placebo separated from randomized groups)
Arm/Group Title Placebo Low Dose Group Medium Dose Group High Dose Group PRN High Group
Arm/Group Description Subjects receiving intranasal Placebo Subjects receiving 10^7 CFU of intranasal BPZE1 Subjects receiving 10^8 CFU of intranasal BPZE1 Subjects receiving 10^9 CFU of intranasal BPZE1 Subjects with a pre-existing baseline PRN > 20 IU that received 10^9 CFU of intranasal BPZE1 (non-randomized group)
Measure Participants 12 12 12 12 6
Cough or Spasmodic Cough of grade >=2
1
8.3%
1
8.3%
1
8.3%
2
16.7%
0
0%
Other respiratory tract AE of grade >=3
0
0%
0
0%
1
8.3%
1
8.3%
0
0%
Other AE grade >=3
0
0%
0
0%
0
0%
0
0%
0
0%
2. Secondary Outcome
Title Proportion of Subjects With BPZE1 Colonization
Description 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.
Time Frame 28 days

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Low Dose Group Medium Dose Group High Dose Group PRN High Group
Arm/Group Description Subjects receiving intranasal Placebo Subjects receiving 10^7 CFU of intranasal BPZE1 Subjects receiving 10^8 CFU of intranasal BPZE1 Subjects receiving 10^9 CFU of intranasal BPZE1 Subjects with a pre-existing baseline PRN > 20 IU that received 10^9 CFU of intranasal BPZE1 (non-randomized group)
Measure Participants 12 12 12 12 6
Colonized
0
0%
10
83.3%
9
75%
10
83.3%
2
33.3%
Not Colonized
12
100%
2
16.7%
3
25%
2
16.7%
4
66.7%
3. Secondary Outcome
Title The Proportion of Subjects That Have an Antibody Response to BPZE1 Vaccination
Description 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.
Time Frame 6 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Low Dose Group Medium Dose Group High Dose Group PRN High Group
Arm/Group Description Subjects receiving intranasal Placebo Subjects receiving 10^7 CFU of intranasal BPZE1 Subjects receiving 10^8 CFU of intranasal BPZE1 Subjects receiving 10^9 CFU of intranasal BPZE1 Subjects with a pre-existing baseline PRN > 20 IU that received 10^9 CFU of intranasal BPZE1 (non-randomized group)
Measure Participants 12 12 12 12 6
Non-responding Subjects
11
91.7%
1
8.3%
4
33.3%
1
8.3%
2
33.3%
1 Antigen
1
8.3%
3
25%
2
16.7%
4
33.3%
1
16.7%
2 Antigens
0
0%
1
8.3%
2
16.7%
3
25%
2
33.3%
3 Antigens
0
0%
4
33.3%
2
16.7%
3
25%
1
16.7%
4 Antigens
0
0%
3
25%
2
16.7%
1
8.3%
0
0%
Non-responding Subjects
10
83.3%
3
25%
5
41.7%
2
16.7%
2
33.3%
1 Antigen
2
16.7%
1
8.3%
2
16.7%
1
8.3%
1
16.7%
2 Antigens
0
0%
3
25%
1
8.3%
6
50%
2
33.3%
3 Antigens
0
0%
3
25%
4
33.3%
3
25%
1
16.7%
4 Antigens
0
0%
2
16.7%
0
0%
0
0%
0
0%
Non-responding Subjects
10
83.3%
1
8.3%
3
25%
0
0%
2
33.3%
1 Antigen
2
16.7%
3
25%
2
16.7%
1
8.3%
0
0%
2 Antigens
0
0%
1
8.3%
0
0%
4
33.3%
1
16.7%
3 Antigens
0
0%
4
33.3%
4
33.3%
4
33.3%
2
33.3%
4 Antigens
0
0%
3
25%
3
25%
3
25%
1
16.7%

Adverse Events

Time Frame 14 days, 1 month, 3 months, 6 months, 1 year
Adverse Event Reporting Description
Arm/Group Title Placebo Low Dose Group Medium Dose Group High Dose Group PRN High Group
Arm/Group Description Subjects receiving intranasal Placebo Subjects receiving 10^7 CFU of intranasal BPZE1 Subjects receiving 10^8 CFU of intranasal BPZE1 Subjects receiving 10^9 CFU of intranasal BPZE1 Subjects with a pre-existing baseline PRN > 20 IU that received 10^9 CFU of intranasal BPZE1 (non-randomized group)
All Cause Mortality
Placebo Low Dose Group Medium Dose Group High Dose Group PRN High Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/6 (0%)
Serious Adverse Events
Placebo Low Dose Group Medium Dose Group High Dose Group PRN High Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/12 (0%) 1/12 (8.3%) 1/12 (8.3%) 0/12 (0%) 0/6 (0%)
Infections and infestations
Pneumonia 0/12 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0 0/12 (0%) 0 0/6 (0%) 0
Renal and urinary disorders
Renal Failure Acute 0/12 (0%) 0 0/12 (0%) 0 1/12 (8.3%) 1 0/12 (0%) 0 0/6 (0%) 0
Other (Not Including Serious) Adverse Events
Placebo Low Dose Group Medium Dose Group High Dose Group PRN High Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 11/12 (91.7%) 11/12 (91.7%) 11/12 (91.7%) 9/12 (75%) 5/6 (83.3%)
General disorders
Fatigue - week 1 6/12 (50%) 5/12 (41.7%) 6/12 (50%) 4/12 (33.3%) 4/6 (66.7%)
Fatigue - Week 2 1/12 (8.3%) 2/12 (16.7%) 2/12 (16.7%) 1/12 (8.3%) 1/6 (16.7%)
Nervous system disorders
Headache - week 1 5/12 (41.7%) 2/12 (16.7%) 6/12 (50%) 3/12 (25%) 3/6 (50%)
Headache - week 2 0/12 (0%) 2/12 (16.7%) 1/12 (8.3%) 3/12 (25%) 0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Cough - week 1 2/12 (16.7%) 4/12 (33.3%) 3/12 (25%) 2/12 (16.7%) 1/6 (16.7%)
Cough - week 2 1/12 (8.3%) 0/12 (0%) 2/12 (16.7%) 2/12 (16.7%) 0/6 (0%)
Nasal Congestion - week 1 3/12 (25%) 6/12 (50%) 4/12 (33.3%) 2/12 (16.7%) 3/6 (50%)
Nasal Congestion - week 2 2/12 (16.7%) 0/12 (0%) 4/12 (33.3%) 0/12 (0%) 1/6 (16.7%)
Rhinorrhoea - week 1 6/12 (50%) 5/12 (41.7%) 4/12 (33.3%) 3/12 (25%) 2/6 (33.3%)
Rhinorrhoea - week 2 2/12 (16.7%) 1/12 (8.3%) 3/12 (25%) 1/12 (8.3%) 0/6 (0%)
Sneezing - week 1 4/12 (33.3%) 7/12 (58.3%) 4/12 (33.3%) 6/12 (50%) 2/6 (33.3%)
Sneezing - week 2 3/12 (25%) 3/12 (25%) 2/12 (16.7%) 3/12 (25%) 0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Publications will be co-authored by the PI and the Sponsor (Inserm).

Results Point of Contact

Name/Title Ken Solovay
Organization ILIAD Biotechnologies
Phone 9543360777
Email ken@iliadbio.com
Responsible Party:
Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier:
NCT02453048
Other Study ID Numbers:
  • C14-80
  • 2015-001287-20
First Posted:
May 25, 2015
Last Update Posted:
Jan 2, 2020
Last Verified:
Jan 1, 2018