First Adult Safety Trial on Nasal Live Attenuated B. Pertussis Vaccine

This study has been completed.
Sponsor:
Collaborators:
European Union
Swedish Institute for Infectious Disease Control
Innogenetics
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier:
NCT01188512
First received: August 24, 2010
Last updated: January 27, 2012
Last verified: January 2012
  Purpose

The purpose of this study is to evaluate the safety and immunogenicity of a new live attenuated vaccine against whooping-cough. It is a phase1, single centre, dose-escalating, placebo-controlled study on a genetically modified B. pertussis strain given as a single intranasal dose to healthy adult male volunteers.

Effective vaccines are needed to protect young infants (from 0 to 6 months, today the most vulnerable age group), preferably after a single administration very early in life. The successful outcome of this project would constitute an important milestone towards nasal vaccination of infants, possibly at birth with a novel, single-dose pertussis vaccine. Our ultimate aim is to protect infants in the most vulnerable age group, before the regular vaccination schedule using already available vaccines is applied. The ultimate aim is thus not to replace current vaccination schedules with available vaccines, but to add a first nasal vaccination to protect very early in life.


Condition Intervention Phase
Pertussis
Biological: BPZE1
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 1, Single Centre, Dose-escalating, Placebo-controlled Study of a Genetically Modified B. Pertussis Strain Given as a Single Intranasal Dose to Healthy Adult Male Volunteers

Resource links provided by NLM:


Further study details as provided by Institut National de la Santé Et de la Recherche Médicale, France:

Primary Outcome Measures:
  • General safety and local tolerability in the respiratory tract of a single ascending dose of the genetically modified B. pertussis strain [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

    To determine

    • general safety, i. e. general well-being of the volunteers and any symptoms felt by the volunteers with onset within one month after vaccine administration.
    • vital signs: Blood pressure, heart rate, respiratory rate, oral temperature.
    • abnormalities in the following 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).


Secondary Outcome Measures:
  • Attachment of the BPZE1 strain to the nasopharyngeal mucosa [ Time Frame: Up to 50 days after vaccination ] [ Designated as safety issue: No ]
    Detection of colonizing BPZE1 bacteria in nasopharyngeal culture

  • Immunogenicity [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Immune responses will be determined by serum IgG and IgA, IgG and IgA in saliva and nasopharyngeal aspirate, cytokines and numbers of effector and memory T and B cells after stimulation with the various B. pertussis antigens.


Enrollment: 48
Study Start Date: August 2010
Study Completion Date: January 2012
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BPZE1 - Low dose
1,000 colony forming units (cfu) of BPZE1
Biological: BPZE1
Individuals will be vaccinated once intranasally with the designated dose of BPZE1 Dose 2 x 0.1 mL (0.1 mL per nostril).
Experimental: BPZE1- middle dose
100,000 colony forming units (cfu) of BPZE1
Biological: BPZE1
Individuals will be vaccinated once intranasally with the designated dose of BPZE1 Dose 2 x 0.1 mL (0.1 mL per nostril).
Experimental: BPZE1 - High dose
10,000,000 colony forming units (cfu) of BPZE1
Biological: BPZE1
Individuals will be vaccinated once intranasally with the designated dose of BPZE1 Dose 2 x 0.1 mL (0.1 mL per nostril).
Placebo Comparator: Placebo
Formulation buffer
Biological: Placebo
Individuals will get placebo once intranasally. Dose 2 x 0.1 mL (0.1 mL per nostril).

  Eligibility

Ages Eligible for Study:   19 Years to 31 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Subject will be included in the study if he meets all the following criteria:

  • Healthy male born between 1979 and 1991 who has not experienced clinical pertussis (lab. Verified) during the past 10 years and who has not been vaccinated with any pertussis vaccine.
  • Informed consent form signed by the subject.
  • Subject shall be able to attend all scheduled visits and to understand and comply with the study procedures (e.g. able to read and write Swedish).

Exclusion Criteria:

If any of the following criteria are met, the subject must not be included in the study:

  • Individuals with pertussis toxin serum IgG antibodies ≥20 units/mL.
  • Blood pressure after resting ≥ 150/90 mmHg.
  • Heart rate after resting ≥80 bpm.
  • Respiratory rate after resting ≥ 20/minute.
  • Unwillingness to refrain from the use of nicotine products from screening through day 28.
  • Use of narcotic drugs/alcohol and/or a history of previous use of drug/alcohol abuse whitin the past 2 years prior to screening
  • 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.
  • Receipt of immunoglobulin, blood derived products, systemic corticosteroids or other immunosuppressant drugs within 90 days prior to day 0.
  • Use of corticosteroids in the respiratory tract(e.g. nasal steroids, inhaled steroids) whitin 30 days prior to day 0.
  • Use of herbal medications or dietary supplements within 7 days prior to day 0 at the discretion of the investigator. Unwillingness to refrain from herbal medications or dietary supplements within 30 days after day 0 at the discretion of the investigator.
  • Receipt of a vaccine within the last 30 days prior to day 0 or planned vaccination within the next 30 days after day 0.
  • Evolving encephalopathy not attributable to another identifiable cause within 7 days of administration of a previous dose of any vaccine.
  • Known hypersensitivity to any component of the study vaccine.
  • 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.
  • Inability to adhere to the protocol, including plans to move from the area.
  • Family history of congenital or hereditary immunodeficiency (first degree).
  • Infection with HIV, hepatitis B or C.
  • Any medical condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
  • Clinically significant abnormal laboratory values at the discretion of the investigator.
  • Person in frequent contact with children less than 1 year of age (father, childcare worker, nurse, etc…) or residence in the same household as persons with known immunodeficiency.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01188512

Locations
Sweden
Karolinska University Hospital
Solna, Sweden, 171 76
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
European Union
Swedish Institute for Infectious Disease Control
Innogenetics
Investigators
Study Director: Camille Locht, PhD Institut National de la Santé Et de la Recherche Médicale, France
Principal Investigator: Nabil Al-Tawil, MD, PhD Karolinska Trial Alliance
Principal Investigator: Rigmor Thorstensson, PhD Swedish Institute for Infectious Disease Control
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT01188512     History of Changes
Other Study ID Numbers: BT06-04, 2010-019936-11
Study First Received: August 24, 2010
Last Updated: January 27, 2012
Health Authority: Sweden: Medical Products Agency

Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:
Live nasal vaccine for prevention of pertussis

Additional relevant MeSH terms:
Whooping Cough
Bordetella Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Respiratory Tract Infections
Infection
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 22, 2014