Safety and Immunogenicity of Intranasal BPZE1 Vaccination in Healthy Adults
Condition: Pertussis; Pertussis Immunisation
MeSH terms: Whooping Cough
Intervention: BPZE1; Placebo
Intervention description: Lyophilized, live-attenuated Bordetella pertussis vaccine reconstituted with sterile water for injection (SWFI) and administered as a single intranasal dose of either 10^7 colony forming units (CFU) or 10^9 CFU.; The placebo consists of the same constituents in the same quantities as the BPZE1 investigational vaccines, absent the attenuated B. pertussis cells, reconstituted with sterile water for injection (SWFI).
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: B. pertussis Vaccine; BPZE1; Immunogenicity; Safety

Summary:

      This is a randomized, partially blind, placebo controlled, clinical trial evaluating a single
      intranasal dose of BPZE1 in healthy adults. The study will evaluate a lyophilized formulation
      of the product, with the goal of testing for the optimal dose for subsequent clinical trials.
      Fifty healthy adults, 18-49 years of age will be randomized to one of the four following
      treatment groups in a 3:3:3:1 ratio: 10^7 colony forming units (CFU) of BPZE1 administered by
      VaxINator device, 10^9 CFU of BPZE1 administered by VaxINator device, placebo administered by
      VaxINator device, 10^9 CFU of BPZE1 administered by needleless tuberculin syringe. Study
      duration will be approximately 12 months with a subject participation duration of
      approximately 6 months. The primary objective of this study is to assess the safety and
      tolerability of a single intranasal dose of either 10^7 or 10^9 CFU of lyophilized BPZE1
      vaccine.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects eligible to participate in this study must meet all inclusion criteria:

          1. Provide written informed consent prior to initiation of any study procedures.

          2. Able to understand and comply with planned study procedures and be available for all
             study visits.

          3. Males or non-pregnant females, 18-49 years of age, inclusive.

          4. In good health*.

             *As determined by medical history and physical examination to evaluate acute or
             currently ongoing chronic medical diagnoses or conditions, defined as those that have
             been present for at least 90 days that would affect the assessment of the safety of
             subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or
             conditions should be stable for the last 60 days. This includes no change in chronic
             prescription medication, dose, or frequency because of deterioration of the chronic
             medical diagnosis or condition in the 60 days prior to enrollment. Any prescription
             change that is due to change of health care provider, insurance company, etc., or that
             is done for financial reasons, if it is in the same class of medication, will not be
             considered a deviation of this inclusion criterion. Any change in prescription
             medication due to improvement of a disease outcome, as determined by the site
             principal investigator or appropriate sub-investigator, will not be considered a
             deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn)
             medications if, in the opinion of the site principal investigator or appropriate
             sub-investigator, they pose no additional risk to subject safety or assessment of
             reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis
             or condition. Similarly, medication changes after enrollment and study vaccination are
             acceptable provided there was no deterioration in the subject's chronic medical
             condition that necessitated a medication change, and there is no additional risk to
             the subject or interference with the evaluation of responses to study vaccination.
             Note: Topical and inhaled medications (with the exception of inhaled or nasal
             corticosteroids within 30 days prior to enrollment), herbals, vitamins, and
             supplements are permitted.

          5. Oral temperature is < / = 100 degrees Fahrenheit.

          6. Pulse is 45 to 100 bpm, inclusive*. *Pulse can be 45 to 50 bpm, inclusive, if no other
             symptoms are present. Otherwise, pulse should be 50-100 bpm.

          7. Systolic blood pressure is 85 to 150 mm Hg, inclusive.

          8. Diastolic blood pressure is 55 to 95 mm Hg, inclusive.

          9. White blood cell count is 3,900 cells/microliter or greater*.

             *Abnormalities in white blood count, hemoglobin, platelet count, alanine
             aminotransferase, and serum creatinine that are suspected to be due to laboratory
             anomalies may be repeated once to ensure accuracy; additionally, otherwise eligible
             subjects with grade 1 abnormalities in these values may be considered for enrollment
             if, in the opinion of the investigator (or clinician on the 1572), the abnormalities
             are not clinically significant and do not pose additional risk to the study or the
             volunteer.

         10. Hemoglobin is 13.0 g/dL or greater (men) or 11.8 g/dL or greater (women)*.
             *Abnormalities in white blood count, hemoglobin, platelet count, alanine
             aminotransferase, and serum creatinine that are suspected to be due to laboratory
             anomalies may be repeated once to ensure accuracy; additionally, otherwise eligible
             subjects with grade 1 abnormalities in these values may be considered for enrollment
             if, in the opinion of the investigator (or clinician on the 1572), the abnormalities
             are not clinically significant and do not pose additional risk to the study or the
             volunteer.

         11. Platelet count is 135,000 cells/microliter or greater*.

             *Abnormalities in white blood count, hemoglobin, platelet count, alanine
             aminotransferase, and serum creatinine that are suspected to be due to laboratory
             anomalies may be repeated once to ensure accuracy; additionally, otherwise eligible
             subjects with grade 1 abnormalities in these values may be considered for enrollment
             if, in the opinion of the investigator (or clinician on the 1572), the abnormalities
             are not clinically significant and do not pose additional risk to the study or the
             volunteer.

         12. Alanine aminotransferase is < 45 U/L (women) or 62 U/L (men)*.

             *Abnormalities in white blood count, hemoglobin, platelet count, alanine
             aminotransferase, and serum creatinine that are suspected to be due to laboratory
             anomalies may be repeated once to ensure accuracy; additionally, otherwise eligible
             subjects with grade 1 abnormalities in these values may be considered for enrollment
             if, in the opinion of the investigator (or clinician on the 1572), the abnormalities
             are not clinically significant and do not pose additional risk to the study or the
             volunteer.

         13. Serum creatinine is < / = 1.25 mg/dL (men) or 1.11 mg/dL (women)*.

             *Abnormalities in white blood count, hemoglobin, platelet count, alanine
             aminotransferase, and serum creatinine that are suspected to be due to laboratory
             anomalies may be repeated once to ensure accuracy; additionally, otherwise eligible
             subjects with grade 1 abnormalities in these values may be considered for enrollment
             if, in the opinion of the investigator (or clinician on the 1572), the abnormalities
             are not clinically significant and do not pose additional risk to the study or the
             volunteer.

         14. Negative serum HIV antibody assay.

         15. Women of childbearing potential* must use an acceptable contraception method** from 30
             days before study vaccination until 60 days after vaccination.

             *Not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy,
             hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal
             sterilization) with documented radiological confirmation test at least 90 days after
             the procedure, and still menstruating or < 1 year has passed since the last menses if
             menopausal.

               -  Includes non-male sexual relationships, abstinence from sexual intercourse with a
                  male partner, monogamous relationship with vasectomized partner who has been
                  vasectomized for 180 days or more prior to the subject receiving study
                  vaccination, barrier methods such as condoms or diaphragms/cervical caps with
                  spermicide, effective intrauterine devices, NuvaRing(R), and licensed hormonal
                  methods such as implants, injectables or oral contraceptives ("the pill").

         16. Women of childbearing potential must have a negative urine or serum pregnancy test
             within 24 hours prior to study vaccination.

        Exclusion Criteria:

          1. Have immunosuppression as a result of an underlying illness or treatment, or use of
             anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study
             vaccination.

          2. Have known or suspected active chronic autoinflammatory condition.

          3. Have known active neoplastic disease (excluding non-melanoma skin cancer) or a history
             of any hematologic malignancy.

          4. Have a history of persistent asthma, major anatomic nasopharyngeal abnormality, or
             sinus polyp disease due to chronic sinusitis*.

             *If a patient has a history of nasopharyngeal surgery such as, but not limited to
             rhinoplasty, tonsillectomy or sinus surgery, adequate healing time per the judgement
             of the investigator must occur prior to enrollment.

          5. Have known hepatitis B or hepatitis C infection.

          6. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.

          7. Currently untreated or clinically unstable (in the opinion of the investigator)
             schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with
             subject compliance or safety evaluations.

          8. Have been hospitalized for psychiatric illness, history of suicide attempt, or
             confinement for danger to self or others within 5 years prior to study vaccination.

          9. Have received corticosteroids (including oral, parenteral, inhaled, nasal, or
             intra-articular) of any dose within 30 days prior to study vaccination.

         10. Individual with PT serum IgG antibodies > / = 20 IU/mL and / or PRN serum IgG
             antibodies > / = 125 IU/ml.

         11. Unwilling to refrain from smoking tobacco for 28 days post vaccination.

         12. Receipt of immunoglobulin or blood derived products within 90 days of enrollment.

         13. Receipt of a vaccine against pertussis in the past 2 years.

         14. Receipt of a live vaccine within 30 days of study vaccination or an inactivated
             vaccine within 14 days of study vaccination.

         15. Planned vaccination with a licensed vaccine within 28 days of study vaccination.

         16. History of severe allergic reaction (e.g., anaphylaxis) or Bell's palsy, or
             Guillain-Barre syndrome, after a previous dose of any diphtheria toxoid-tetanus
             toxoid-, or pertussis-containing vaccine, or encephalopathy within 7 days of
             administration of a previous pertussis containing vaccine.

         17. History of a progressive neurologic disorder.

         18. In close contact* with children less than 1 year of age or contact with persons with
             known immunocompromising conditions.

             *Close contact includes sharing a household, serving as a healthcare worker, or
             working professionally in settings with repeated exposures.

         19. Receipt of B. pertussis-active antibiotics* within 7 days prior to vaccination.

             *B. pertussis active antibiotics include macrolides, fluoroquinolones,
             trimethoprim-sulfamethoxazole, tetracyclines.

         20. Known hypersensitivity to any component of the study vaccine.

         21. Hypersensitivity to azithromycin, which may be used in the event of ongoing BPZE1
             colonization.

         22. Any condition that, in the opinion of the investigator, might interfere with
             objectives of the study or safety to the individual.

         23. Acute illness, including temperature > 100 degrees Fahrenheit within one week prior to
             vaccination*.

               -  Enrollment may be postponed if acute illness occurs; subjects must remain within
                  the screening window, however, and must be rescreened if > 30 days elapses prior
                  to enrollment.