Safety and Immunogenicity of Intranasal BPZE1 Vaccination in Healthy Adults

NCT03541499 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 17-0010
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pertussis; Pertussis Immunisation

Keywords

B. pertussis Vaccine; BPZE1; Immunogenicity; Safety

Outcome Measures

Primary Outcomes (8)

• Number of Participants Experiencing Adverse Events of Special Interest (AESIs)

  AESIs included medically attended wheezing events given the route of study product administration and the nature of the study product.

  Day 1 through Day 29

• Number of Participants Experiencing New Onset Chronic Medical Conditions (NOCMCs)

  NOCMCs are defined as new medical conditions, not present at the time of screening or enrollment, that require ongoing medical care and intervention.

  Day 1 through Day 181

• Number of Participants Experiencing Serious Adverse Events (SAEs)

  An adverse event was considered serious if, in the view of either the site principal investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect, or, when, based upon appropriate medical judgment they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

  Day 1 through Day 181

• Number of Participants Experiencing Solicited Local Reactogenicity Adverse Events (AEs)

  The solicited local reactogenicity events included runny nose, stuffy nose/congestion, nasal pain/irritation, epistaxis, sneezing, sinus pressure/pain, sore/irritated throat, cough, and shortness of breath/wheezing.

  Day 1 through Day 15

• Number of Participants Experiencing Solicited Systemic Reactogenicity AEs

  The solicited systemic reactogenicity events included fever, feverishness, fatigue, malaise, myalgia, arthralgia, headache, and rash/hypersensitivity.

  Day 1 through Day 15

• Number of Participants Experiencing Unsolicited Non-Serious AEs

  Adverse events were defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Unsolicited non-serious AEs were documented and reported from the time of vaccination through Day 29.

  Day 1 through Day 29

• Number of Participants Experiencing Severe Solicited Local Reactogenicity Adverse Events

  Solicited local reactogenicity events include runny nose, stuffy nose/congestion, nasal pain/irritation, epistaxis, sneezing, sinus pressure/pain, sore/irritated throat, cough, and shortness of breath/wheezing. They were graded as grade 1 (mild), grade 2 (moderate), or grade 3 (severe). Severe local events were those that required medical care or caused significant discomfort that prevented daily activity, including sore/irritated throat preventing eating or drinking and cough preventing sleep. Severe epistaxis events were bleeding events that required a medical encounter. Severe stuffy nose/congestion events caused the participant to be unable to breathe through the nose or to seek medical care.

  Day 1 through Day 15

• Number of Participants Experiencing Severe Solicited Systemic Reactogenicity AEs

  Solicited systemic reactogenicity events include fever, feverishness, fatigue, malaise, myalgia, arthralgia, headache, and rash/hypersensitivity. They were graded as grade 1 (mild), grade 2 (moderate), and grade 3 (severe). For all symptoms except rash and fever, an event was considered severe if it caused significant interference and prevented daily activity. Severe rash/hypersensitivity events were those that caused generalized urticaria, anaphylaxis, or angioedema or localized urticaria that required medical encounter. Severe fever was a temperature exceeding 38.9°C.

  Day 1 through Day 15

Secondary Outcomes (28)

• Geometric Mean Fold Rise From Screening of the Ratio of Filamentous Hemagglutinin-specific IgA (FHA-IgA) to Total IgA by Nasal Aspirate

  Screening, Day 29, Day 181

• Geometric Mean Fold Rise From Screening of the Ratio of Fimbriae-Specific IgA (FIM-IgA) to Total IgA by Nasal Aspirate

  Screening, Day 29, and Day 181

• Geometric Mean Fold Rise From Screening of the Ratio of Pertactin-Specific IgA (PRN-IgA) to Total IgA by Nasal Aspirate

  Screening, Day 29, and Day 181

• Geometric Mean Fold Rise From Screening of the Ratio of Pertussis Toxin-Specific IgA (PT-IgA) to Total IgA by Nasal Aspirate

  Screening, Day 29, and Day 181

• Geometric Mean Fold Rise From Baseline Serum IgA and Serum IgG ELISA Titers to Filamentous Hemagglutinin (FHA)

  Day 1, Day 15, Day 29, and Day 181

Study Arms (4)

Group 1

EXPERIMENTAL

800 microliters (10\^7 CFU) of B. pertussis vaccine (BPZE1) administered intranasally with the VaxINator device on Day 1, n=15

Biological: BPZE1

Group 2

EXPERIMENTAL

800 microliters (10\^9 CFU) of BPZE1 administered intranasally with the VaxINator device on Day 1, n=15

Biological: BPZE1

Group 3

PLACEBO COMPARATOR

800 microliters of Placebo administered intranasally with the VaxINator device on Day 1, n=15

Other: Placebo

Group 4

EXPERIMENTAL

800 microliters (10\^9 CFU) of BPZE1 administered intranasally with a needleless tuberculin syringe on Day 1, n=5

Biological: BPZE1

Interventions

BPZE1 BIOLOGICAL

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.

Group 1; Group 2; Group 4

Placebo OTHER

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).

Group 3

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent prior to initiation of any study procedures.
• Able to understand and comply with planned study procedures and be available for all study visits.
• Males or non-pregnant females, 18-49 years of age, inclusive.
• In good health\*.
• Oral temperature is \< / = 100 degrees Fahrenheit.
• 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.
• Systolic blood pressure is 85 to 150 mm Hg, inclusive.
• Diastolic blood pressure is 55 to 95 mm Hg, inclusive.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• Have known or suspected active chronic autoinflammatory condition.
• Have known active neoplastic disease (excluding non-melanoma skin cancer) or a history of any hematologic malignancy.
• 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.
• Have known hepatitis B or hepatitis C infection.
• Have a history of alcohol or drug abuse within 5 years prior to study vaccination.
• 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.
• 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.
• Have received corticosteroids (including oral, parenteral, inhaled, nasal, or intra-articular) of any dose within 30 days prior to study vaccination.
• Individual with PT serum IgG antibodies \> / = 20 IU/mL and / or PRN serum IgG antibodies \> / = 125 IU/ml.
• Unwilling to refrain from smoking tobacco for 28 days post vaccination.
• Receipt of immunoglobulin or blood derived products within 90 days of enrollment.
• Receipt of a vaccine against pertussis in the past 2 years.
• Receipt of a live vaccine within 30 days of study vaccination or an inactivated vaccine within 14 days of study vaccination.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

Nashville, Tennessee, 37232-2573, United States

Location

MeSH Terms

Conditions

Whooping Cough

Condition Hierarchy (Ancestors)

Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. C Buddy Creech
• Organization: Vanderbilt Vaccine Research Program

buddy.creech@vanderbilt.edu

615-3430332

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2018
• First Posted: May 30, 2018
• Study Start: October 23, 2018
• Primary Completion: May 15, 2020
• Study Completion: May 15, 2020
• Last Updated: September 19, 2024
• Results First Posted: February 3, 2022

Record last verified: 2021-08-18

Locations

US (1)