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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

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.

Detailed Summary:
Sponsor: Institut National de la Santé Et de la Recherche Médicale, France

Current Primary Outcome: Proportion of subjects with blood laboratory abnormalities and respiratory tract adverse events [ Time Frame: 6 months ]

Proportion is based on subjects experiencing at least one of the following events:

  • abnormalities in laboratory data: Haemoglobin, total and differential white blood cell count, platelets (thrombocytes).
  • specific side effects: Local symptoms from the respiratory tract: Sneezing, swollen nose, cough, bleeding from the nose, pain or other symptoms from the ear, symptoms from the eyes (redness, secretion).

Safety parameters are measured before vaccination and at 4, 7, 11, 14, 21, 28 days and 6-months post-vaccination.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Proportion of subjects with BPZE1 Colonization [ Time Frame: 28 days ]
    To assess the proportion of subjects having positive colonization of the human respiratory tract by live attenuated B. pertussis strain BPZE1 and to quantify the average number of colony forming units (cfu) per group at each time period. Colonization is measured at 4, 7, 11, 14, 21 and 28 days post vaccination.
  • The proportion of subjects that have an antibody response to BPZE1 vaccination [ Time Frame: 12 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.

    Antibodies are measured before vaccination and at 4, 7, 11, 14, 21, 28 days, 6-months and 12-months post-vaccination.

  • The proportion of High PRN Antibody level subjects that have an immune response to BPZE1 vaccination [ Time Frame: 6 months ]

    To assess the number of immune responders and levels of IgG/IgA antibodies to PT, FHA, PRN, and fimbriae 2/3 in serum and nasopharyngeal aspirate in a group of subjects with high anti-PRN antibody levels.

    A positive antibody response after vaccination is defined as at least 100% increase from pre- to post-vaccination, to at least 4 times MLD (minimum level of detection) for PT, FHA, PRN, and fimbriae 2/3 in the post-vaccination sample.

    Antibodies are measured before vaccination and at 4, 7, 11, 14, 21, 28 days and 6-months post-vaccination.



Original Secondary Outcome:

  • Proportion of subjects with BPZE1 Colonization [ Time Frame: 28 days ]
    To assess the proportion of subjects having positive colonization of the human respiratory tract by live attenuated B. pertussis strain BPZE1 and to quantify the average number of colony forming units (cfu) per group at each time period. Colonization is measured at 4, 7, 11, 14, 21 and 28 days post vaccination.
  • The proportion of subjects that have an antibody response to BPZE1 vaccination [ Time Frame: 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.

    Antibodies are measured before vaccination and at 4, 7, 11, 14, 21, 28 days and 6-months post-vaccination.

  • The proportion of High PRN Antibody level subjects that have an immune response to BPZE1 vaccination [ Time Frame: 6 months ]

    To assess the number of immune responders and levels of IgG/IgA antibodies to PT, FHA, PRN, and fimbriae 2/3 in serum and nasopharyngeal aspirate in a group of subjects with high anti-PRN antibody levels.

    A positive antibody response after vaccination is defined as at least 100% increase from pre- to post-vaccination, to at least 4 times MLD (minimum level of detection) for PT, FHA, PRN, and fimbriae 2/3 in the post-vaccination sample.

    Antibodies are measured before vaccination and at 4, 7, 11, 14, 21, 28 days and 6-months post-vaccination.



Information By: Institut National de la Santé Et de la Recherche Médicale, France

Dates:
Date Received: May 18, 2015
Date Started: September 2015
Date Completion: December 2017
Last Updated: September 6, 2016
Last Verified: October 2015