Study of BPZE1 Intranasal Pertussis Vaccine (Administered Via VaxINator(TM)), Prime + Boost, in Healthy Adults

June 25, 2023 updated by: ILiAD Biotechnologies

Phase 2b Study of BPZE1 Intranasal Pertussis Vaccine in Adults to Assess Immunological Response and Safety Profile of 1-Dose (Prime) and 2-Doses (Prime+Boost) Schedule, Compared to a Boostrix™ Prime Dose With or Without a BPZE1 Boost Dose

This study evaluates the safety and immunogenicity of the BPZE1 live attenuated pertussis vaccine, intended to prevent nasopharyngeal colonization and pertussis disease, and compares a single (prime) BPZE1 dose or BPZE1 2-dose (prime + boost) to a single (prime) Boostrix or Boostrix prime + BPZE1 boost.

Study Overview

Detailed Description

This study evaluates the safety and immunogenicity of the BPZE1 live attenuated pertussis vaccine, intended to prevent nasopharyngeal colonization and pertussis disease, and compares a single (prime) BPZE1 dose or BPZE1 2-dose (prime + boost) to a single (prime) Boostrix or Boostrix prime + BPZE1 boost. This is a multi-center, randomized, placebo-controlled, and observer blinded trial in healthy adults with a 6 month safety follow-up after the last vaccination.

Study Type

Interventional

Enrollment (Actual)

300

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ohio
      • Cleveland, Ohio, United States, 44122
        • Rapid Medical Research Inc
    • Texas
      • Tomball, Texas, United States, 77375
        • DM Clinical Research
    • Utah
      • West Jordan, Utah, United States, 84088
        • Advanced Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Is a male or nonpregnant female 18 to 50 years of age, inclusive, on Day 1 (primary vaccination).
  2. Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
  3. Female subjects must be nonpregnant and nonlactating and meet 1 of the following criteria:

    1. Postmenopausal (defined as 12 consecutive months with no menses without an alternative medical cause or documented plasma follicle-stimulating hormone level in the postmenopausal range);
    2. Surgically sterile (ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy).

      NOTE: These procedures and laboratory test results must be confirmed by physical examination, or by subject recall of specific date and hospital/facility of procedure, or by medical documentation of said procedure.

    3. Is of childbearing potential (defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal), agrees to be heterosexually inactive from at least 21 days prior to enrollment and through 3 months after the boosting vaccination or agrees to consistently use any of the following methods of contraception from at least 21 days prior to enrollment and through 3 months after the boosting vaccination:

    i. Condoms (male or female) with spermicide ii. Diaphragm with spermicide iii. Cervical cap with spermicide iv. Intrauterine device v. Oral or patch contraceptives vi. Norplant®, Depo-Provera®, or other FDA approved contraceptive method that is designed to protect against pregnancy.

    NOTE: Periodic abstinence (eg, calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception.

  4. Has a stable health status as assessed by the investigator, as established by physical examination, vital sign measurements, and medical history.
  5. Has access to a consistent and reliable means of telephone contact, which may be in the home, workplace, or by personal mobile electronic device.
  6. Is able to understand and comply with planned study procedures.
  7. Lives a reasonable distance from the clinical site to be able to travel to and from the clinical site for follow-up visits and agrees to go to the clinical site for evaluation (or provide medical record access if evaluated elsewhere) in the event of an AE.
  8. Agrees to stay in contact with the clinical site for the duration of the study, has no current plans to move from the study area, and provides updated contact information as necessary.

Exclusion Criteria:

  1. History of being vaccinated in the past 5 years against pertussis.
  2. Any significant past reaction to any component of Boostrix (at the discretion of the investigator).
  3. Subject reported diagnosis of pertussis in the past 10 years (must be laboratory confirmed or physician diagnosed from medical records).
  4. Vital signs by FDA toxicity scoring >1 (may be repeated once during the screening period to allow for inclusion and the most recent measurement taken at baseline).
  5. Chronic illness being treated actively and with evidence of recent intervention for worsening or fluctuating symptoms (at the discretion of the investigator).
  6. The subject has a history of active cancer (malignancy) in the last 10 years (exception is subjects with adequately treated non melanomatous skin carcinoma, who may participate in the study).
  7. Current use of any smoking products and unwillingness to refrain from the use of any smoking products from screening through 28 days after the boosting vaccination.
  8. Use of narcotic drugs, evidenced by urine toxicology screen or a history of drug/alcohol abuse within the past 2 years.
  9. Has donated blood or suffered from blood loss of more than 450 mL (1 unit of blood) within 60 days prior to screening or donated plasma within 14 days prior to screening.
  10. Receipt of immunoglobulin, blood-derived products, systemic corticosteroids, or other immunosuppressant drugs within 90 days prior to Day 1.
  11. Asthma, obstructive nasal canal, recurrent or acute sinusitis or other chronic respiratory problems inclusive of the diagnosis of any significant pulmonary disease.
  12. History of nasal surgery or Bell's palsy.
  13. Use of repeated nasal sprays, Neti pot, routine nasal washing within the past 1 month (more than 2 times per week). Subjects must agree to refrain from use of any of these modalities through Day 113.
  14. A temporary exclusion to vaccinate if acute respiratory tract infection or rhinorrhea or temperature >100.4°F (no symptoms for 3 days prior to vaccination day). Subjects may be vaccinated if they stay within the vaccination window (screening [30 days] or at the time of the booster [10 days]).

    NOTE: If a subject exceeds the screening window, they must be reconsented and screening must be reinitiated.

  15. Use of corticosteroids in the respiratory tract (eg, nasal steroids, inhaled steroids) within 30 days prior to Day 1.
  16. Receipt of a licensed vaccine within the last 30 days prior to Day 1 or planned vaccination during the active study conduct through Day 113. In the case of seasonal influenza, vaccination should not be withheld and is not contraindicated for subject participation. However, vaccination should be planned outside of a 30 day pre- and 30 day post vaccination window whenever possible.
  17. Known hypersensitivity to any component of the study vaccines.
  18. Participation in any other clinical trial for the testing of an unlicensed product during the previous 6 months or planned during the study conduct.
  19. Inability to adhere to the protocol, including plans to move from the area.
  20. Personal history or family (first degree) history of congenital or hereditary immunodeficiency.
  21. Past or present infection with human immunodeficiency virus, hepatitis B, or hepatitis C by screening test.
  22. Any autoimmune or immunodeficiency disease/condition (inherited or iatrogenic).
  23. Any neurological disease or history of significant neurological disorder (eg, meningitis, seizures, multiple sclerosis, vasculitis, migraines, Guillain-Barré syndrome [genetic/congenital or acquired]).
  24. Any medical condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives or might affect the safety of the individual, (eg, major depression or history of suicidal attempt).
  25. Toxicity grading >1 for screening laboratory test results for kidney, hepatic, and hematologic values (may be repeated once during the screening period to allow for inclusion and the most recent measurement taken at baseline). See Table 13 2 for specifically designated parameters.
  26. Body mass index <17 kg/m2 or >40 kg/m2.
  27. 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.
  28. Study team member or first-degree relative of study team member.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BPZE1 Intranasal Prime, BPZE1 Boost
Individual will receive an intranasal dose of BPZE1 via the VaxINator atomization device and a dose of intramuscular (I.M.) placebo. Individuals will receive a boost dose of intranasal BPZE1 via the VaxINator™ atomization device.
Live attenuated pertussis vaccine administered via the VaxINator(TM) atomization device
Experimental: BPZE1 Intranasal Prime, Placebo Boost
Individual will receive an intranasal dose of BPZE1 via the VaxINator atomization device and a dose of intramuscular (I.M.) placebo. Individuals will receive a boost dose of intranasal placebo via the VaxINator™ atomization device.
Live attenuated pertussis vaccine administered via the VaxINator(TM) atomization device
Experimental: Boostrix IM Prime, BPZE1 Boost
Individual will receive an intranasal dose of placebo via the VaxINator atomization device and a dose of intramuscular (I.M.) Boostrix (aP vaccine comparator). Individuals will receive a boost dose of intranasal BPZE1 via the VaxINator™ atomization device.
Live attenuated pertussis vaccine administered via the VaxINator(TM) atomization device
Active Comparator: Boostrix IM Prime, Placebo Boost
Individual will receive an intranasal dose of placebo via the VaxINator atomization device and a dose of intramuscular (I.M.) Boostrix (aP vaccine comparator). Individuals will receive a boost dose of intranasal placebo via the VaxINator™ atomization device.
Live attenuated pertussis vaccine administered via the VaxINator(TM) atomization device

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Nasal Mucosal Seroconversion (Immunoglobulin A [IgA])
Time Frame: Days 29 and 113
Number of participants who achieve mucosal seroconversion (IgA) against at least 1 anti-pertussis antibody for whole cell extract (WCE), pertussis toxin (PT), filamentous hemagglutinin (FHA), or pertactin (PRN) on Day 29 or Day 113. Mucosal seroconversion was defined as a 2-fold increase over the baseline value or a 4-fold increase over the minimal detection limit of the assay (whenever the baseline value was below the detection limits of the assay).
Days 29 and 113
Safety - Number of Participants With Nasal/Respiratory Solicited Adverse Events (AEs)
Time Frame: Through 7 Days Following Day 1 Vaccination
Number of participants with Solicited AEs (nasal/respiratory reactogenicity events) by Grade - Any Day Grade 1 through 3 and Grade 3. Grading of reactogenicity is defined per protocol as Grade 1 (mild), Grade 2 (moderate), and Grade 3 (severe) AEs.
Through 7 Days Following Day 1 Vaccination
Safety - Number of Participants With Local Solicited AEs
Time Frame: Through 7 Days Following Day 1 Vaccination
Number of participants with Solicited AEs (local reactogenicity events) by Grade - Any Day Grade 1 through 4 and Grade 3 and 4. Grading of reactogenicity is defined per protocol as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), and Grade 4 (potentially life-threatening) AEs.
Through 7 Days Following Day 1 Vaccination
Safety - Number of Participants With Systemic Solicited AEs
Time Frame: Through 7 Days Following Day 1 Vaccination
Number of participants with Solicited AEs (systemic reactogenicity events) by Grade - Any Day Grade 1 through 3 and Grade 3. Grading of reactogenicity is defined per protocol as Grade 1 (mild), Grade 2 (moderate), and Grade 3 (severe) AEs.
Through 7 Days Following Day 1 Vaccination
Safety Lead-in Participants With Abnormal Laboratory Parameters (BPZE1 10^7 Safety Lead-In)
Time Frame: Days 8 and 92
Number of participants in the safety lead-in cohort with Grade 2 through 4 laboratory abnormalities: Serum Chemistry - Bilirubin, Creatinine, ALT, AST; WBC, Hemoglobin, Prothrombin time, Partial Thromboplastin Time. Grading of laboratory results is defined per protocol as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (potentially life-threatening) laboratory abnormalities (DHHS 2007).
Days 8 and 92

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Systemic Immunogenicity - Summary of Systemic IgG Seroconversion Endpoints
Time Frame: 9 months
Number of participants who achieve seroconversion (serum IgG) against 1 or more pertussis antigens (pertussis toxin [PT], filamentous hemagglutinin [FHA], pertactin [PRN], or whole cell extract [WCE]) on Days 29, 85, 113, 169, and/or 254. Systemic seroconversion was defined as a 2-fold increase over the baseline value or a 4-fold increase over the minimal detection limit of the assay (whenever the baseline value fell below the detection limits of the assay).
9 months
Systemic Immunogenicity - Summary of Systemic IgA Seroconversion Endpoints
Time Frame: 9 Months
Number of participants who achieve seroconversion (serum IgA) against 1 or more pertussis antigens (PT, FHA, PRN) on Days 29, 85, 113, 169, and/or 254. Systemic seroconversion was defined as a 2-fold increase over the baseline value or a 4-fold increase over the minimal detection limit of the assay (whenever the baseline value fell below the detection limits of the assay).
9 Months
Systemic Immunogenicity - Summary of Geometric Mean Fold Rises (GMFRs) of Systemic IgG Against Whole Cell Extract by Vaccine Group and Time Point
Time Frame: Days 29 and 85
Systemic Immunogenicity: Summary of GMFRs of Systemic IgG Against Whole Cell Extract by Vaccine Group and Time Point - GMFRs on Day 29 and Day 85 over baseline (Day 1)
Days 29 and 85
Systemic Immunogenicity - Summary of GMFRs of Systemic IgG Against Whole Cell Extract by Vaccine Group and Time Point
Time Frame: Days 113, 169 and 254
Systemic Immunogenicity: Summary of GMFRs of Systemic IgG Against Whole Cell Extract by Vaccine Group and Time Point - GMFRs on Days 113, 169, and 254 over baseline (Day 1)
Days 113, 169 and 254
Mucosal Immunogenicity - Summary of Mucosal Absolute S-IgA/Total S-IgA Seroconversion Endpoints
Time Frame: 9 months
Number of participants who achieve seroconversion against any pertussis specific antigen (PT, PRN, FHA, or WCE) in nasal secretions (S-IgA). Mucosal seroconversion was defined as a 2-fold increase over the baseline value or a 4-fold increase over the minimal detection limit of the assay (whenever the baseline value was below the detection limits of the assay).
9 months
Mucosal Immunogenicity - Summary of GMFRs of Mucosal Absolute S-IgA/Total S-IgA Against Whole Cell Extract by Vaccine Group and Time Point
Time Frame: Days 29 and 78
Mucosal Immunogenicity: Summary of GMFRs of Mucosal Absolute S-IgA/Total S-IgA Against Whole Cell Extract by Vaccine Group and Time Point - GMFRs on Day 29 and Day 78 over baseline (Day 1)
Days 29 and 78
Mucosal Immunogenicity - Summary of GMFRs of Mucosal Absolute S-IgA/Total S-IgA Against Whole Cell Extract by Vaccine Group and Time Point
Time Frame: Days 113, 169, 254
Mucosal Immunogenicity: Summary of GMFRs of Mucosal Absolute S-IgA/Total S-IgA Against Whole Cell Extract by Vaccine Group and Time Point - GMFRs on Day 113, Day 169, and Day 254 over baseline (Day 1)
Days 113, 169, 254
Colonization - Summary of Colonization for B. Pertussis Bacterial Culture From Nasal Sample by Timepoint
Time Frame: Days 92, 96, 113
Number of participants with positive B. pertussis by bacterial culture of nasal sample on any of Days 92, 96, and 113 (colonization)
Days 92, 96, 113
Safety - Number of Participants With Unsolicited AEs
Time Frame: Days 1 through 29

Number of participants with Unsolicited AEs collected Day 1 to Day 29 by Medical Dictionary for Regulatory Activities (MedDRA) classification.

Threshold is greater than or equal to 5% of participants.

Days 1 through 29
Safety - Number of Participants With Unsolicited AEs
Time Frame: Days 85 through 113

Number of participants with Unsolicited AEs Day 85 through Day 113 by MedDRA classification.

Threshold is greater than or equal to 5% of participants.

Days 85 through 113
Safety - Number of Participants With Serious AEs
Time Frame: Days 1 to 84
Number of participants with Serious AEs collected on Day 1 through Day 84 by MedDRA classification.
Days 1 to 84
Safety - Number of Participants With Serious AEs
Time Frame: Days 85 to 113
Number of participants with Serious AEs collected on Day 85 through Day 113 by MedDRA classification.
Days 85 to 113
Safety - Number of Participants With Serious AEs
Time Frame: Days 114 to 254 (end of study)
Number of participants with Serious AEs collected on Day 114 through Day 254 by MedDRA classification.
Days 114 to 254 (end of study)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exploratory - Cell-mediated Responses
Time Frame: 1 month post vaccination
Cell-mediated (eg, B cell, CD4 T lymphocytes + T cell, CD8 T lymphocytes + T cell) responses (eg, cell staining, cytokine production) following stimulation of peripheral blood mononuclear cells collected at baseline, and 8 days post vaccination (prime and boost) to pertussis specific antigens. Results expressed both as absolute values and fold over baseline (per specific assay characteristics).
1 month post vaccination
Exploratory - additional mucosal immunity
Time Frame: 1 month post vaccination
Following the outcomes of the primary and second analyses, additional exploratory endpoints may be tested for systemic or nasal mucosal immunogenicity (IgG or IgA) responses at any time point collected and not already performed in the primary or secondary analysis sets.
1 month post vaccination
Exploratory - Geometric Mean Titer IgG for Tetanus and Diptheria
Time Frame: 1 month post vaccination
The Geometric Mean Titer, expressed for serum IgG ELISA against tetanus and diphtheria on Days 29 and 113.
1 month post vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

PPD

Investigators

  • Principal Investigator: Mary B Manning, MD, Rapid Medical Research Inc
  • Principal Investigator: Barbara Rizzardi, MD, Advanced Clinical Research
  • Principal Investigator: Vicki Miller, MD, DM Clinical Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2019

Primary Completion (Actual)

February 14, 2020

Study Completion (Actual)

June 24, 2020

Study Registration Dates

First Submitted

May 2, 2019

First Submitted That Met QC Criteria

May 6, 2019

First Posted (Actual)

May 8, 2019

Study Record Updates

Last Update Posted (Actual)

June 27, 2023

Last Update Submitted That Met QC Criteria

June 25, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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