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

NCT03942406 | Completed Phase 2 Results DMC FDA Drug FDA Device

• 1 other identifier: IB-200P
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Pertussis; Whooping Cough

Keywords

pertussis; Bordetella infection; Gram-negative bacterial infection; Respiratory tract infection; Whooping cough; Infection; Respiratory tract disease; Vaccine; Immunological factors; Physiological effects of drugs

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Nasal Mucosal Seroconversion (Immunoglobulin A [IgA])

  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)

  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

  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

  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)

  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 Outcomes (13)

• Systemic Immunogenicity - Summary of Systemic IgG Seroconversion Endpoints

  9 months

• Systemic Immunogenicity - Summary of Systemic IgA Seroconversion Endpoints

  9 Months

• Systemic Immunogenicity - Summary of Geometric Mean Fold Rises (GMFRs) of Systemic IgG Against Whole Cell Extract by Vaccine Group and Time Point

  Days 29 and 85

• Systemic Immunogenicity - Summary of GMFRs of Systemic IgG Against Whole Cell Extract by Vaccine Group and Time Point

  Days 113, 169 and 254

• Mucosal Immunogenicity - Summary of Mucosal Absolute S-IgA/Total S-IgA Seroconversion Endpoints

  9 months

Study Arms (4)

BPZE1 Intranasal Prime, BPZE1 Boost

EXPERIMENTAL

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.

Combination Product: BPZE1 pertussis vaccine and VaxINator(TM) Atomization Device

BPZE1 Intranasal Prime, Placebo Boost

EXPERIMENTAL

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.

Combination Product: BPZE1 pertussis vaccine and VaxINator(TM) Atomization Device

Boostrix IM Prime, BPZE1 Boost

EXPERIMENTAL

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.

Combination Product: BPZE1 pertussis vaccine and VaxINator(TM) Atomization Device

Boostrix IM Prime, Placebo Boost

ACTIVE COMPARATOR

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.

Combination Product: BPZE1 pertussis vaccine and VaxINator(TM) Atomization Device

Interventions

BPZE1 pertussis vaccine and VaxINator(TM) Atomization Device COMBINATION_PRODUCT

Live attenuated pertussis vaccine administered via the VaxINator(TM) atomization device

BPZE1 Intranasal Prime, BPZE1 Boost; BPZE1 Intranasal Prime, Placebo Boost; Boostrix IM Prime, BPZE1 Boost; Boostrix IM Prime, Placebo Boost

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Is a male or nonpregnant female 18 to 50 years of age, inclusive, on Day 1 (primary vaccination).
• Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
• Female subjects must be nonpregnant and nonlactating and meet 1 of the following criteria:
• 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);
• 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.
• 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.
• Has a stable health status as assessed by the investigator, as established by physical examination, vital sign measurements, and medical history.
• Has access to a consistent and reliable means of telephone contact, which may be in the home, workplace, or by personal mobile electronic device.
• Is able to understand and comply with planned study procedures.
• 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.
• 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.

You may not qualify if:

• History of being vaccinated in the past 5 years against pertussis.
• Any significant past reaction to any component of Boostrix (at the discretion of the investigator).
• Subject reported diagnosis of pertussis in the past 10 years (must be laboratory confirmed or physician diagnosed from medical records).
• Chronic illness being treated actively and with evidence of recent intervention for worsening or fluctuating symptoms (at the discretion of the investigator).
• 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).
• 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.
• Use of narcotic drugs, evidenced by urine toxicology screen or a history of drug/alcohol abuse within the past 2 years.
• 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.
• Receipt of immunoglobulin, blood-derived products, systemic corticosteroids, or other immunosuppressant drugs within 90 days prior to Day 1.
• Asthma, obstructive nasal canal, recurrent or acute sinusitis or other chronic respiratory problems inclusive of the diagnosis of any significant pulmonary disease.
• History of nasal surgery or Bell's palsy.
• 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.
• NOTE: If a subject exceeds the screening window, they must be reconsented and screening must be reinitiated.
• Use of corticosteroids in the respiratory tract (eg, nasal steroids, inhaled steroids) within 30 days prior to Day 1.
• 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.

Sponsors & Collaborators

• ILiAD Biotechnologies: lead
• PPD Development, LP: collaborator

Study Sites (3)

Rapid medical Research Inc

Cleveland, Ohio, 44122, United States

Location

DM Clinical Research

Tomball, Texas, 77375, United States

Location

Advanced Clinical Research

West Jordan, Utah, 84088, United States

Location

Related Publications (9)

• Althouse BM, Scarpino SV. Asymptomatic transmission and the resurgence of Bordetella pertussis. BMC Med. 2015 Jun 24;13:146. doi: 10.1186/s12916-015-0382-8.

  PMID: 26103968 BACKGROUND

• Feunou PF, Ismaili J, Debrie AS, Huot L, Hot D, Raze D, Lemoine Y, Locht C. Genetic stability of the live attenuated Bordetella pertussis vaccine candidate BPZE1. Vaccine. 2008 Oct 23;26(45):5722-7. doi: 10.1016/j.vaccine.2008.08.018. Epub 2008 Aug 30.

  PMID: 18762220 BACKGROUND

• Feunou PF, Mielcarek N, Locht C. Reciprocal interference of maternal and infant immunization in protection against pertussis. Vaccine. 2016 Feb 17;34(8):1062-9. doi: 10.1016/j.vaccine.2016.01.011. Epub 2016 Jan 15.

  PMID: 26776471 BACKGROUND

• Locht C, Papin JF, Lecher S, Debrie AS, Thalen M, Solovay K, Rubin K, Mielcarek N. Live Attenuated Pertussis Vaccine BPZE1 Protects Baboons Against Bordetella pertussis Disease and Infection. J Infect Dis. 2017 Jul 1;216(1):117-124. doi: 10.1093/infdis/jix254.

  PMID: 28535276 BACKGROUND

• Mielcarek N, Debrie AS, Raze D, Bertout J, Rouanet C, Younes AB, Creusy C, Engle J, Goldman WE, Locht C. Live attenuated B. pertussis as a single-dose nasal vaccine against whooping cough. PLoS Pathog. 2006 Jul;2(7):e65. doi: 10.1371/journal.ppat.0020065.

  PMID: 16839199 BACKGROUND

• Mielcarek N, Debrie AS, Mahieux S, Locht C. Dose response of attenuated Bordetella pertussis BPZE1-induced protection in mice. Clin Vaccine Immunol. 2010 Mar;17(3):317-24. doi: 10.1128/CVI.00322-09. Epub 2010 Jan 27.

  PMID: 20107007 BACKGROUND

• Skerry CM, Cassidy JP, English K, Feunou-Feunou P, Locht C, Mahon BP. A live attenuated Bordetella pertussis candidate vaccine does not cause disseminating infection in gamma interferon receptor knockout mice. Clin Vaccine Immunol. 2009 Sep;16(9):1344-51. doi: 10.1128/CVI.00082-09. Epub 2009 Jul 22.

  PMID: 19625486 BACKGROUND

• Warfel JM, Zimmerman LI, Merkel TJ. Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model. Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):787-92. doi: 10.1073/pnas.1314688110. Epub 2013 Nov 25.

  PMID: 24277828 BACKGROUND

• Keech C, Miller VE, Rizzardi B, Hoyle C, Pryor MJ, Ferrand J, Solovay K, Thalen M, Noviello S, Goldstein P, Gorringe A, Cavell B, He Q, Barkoff AM, Rubin K, Locht C. Immunogenicity and safety of BPZE1, an intranasal live attenuated pertussis vaccine, versus tetanus-diphtheria-acellular pertussis vaccine: a randomised, double-blind, phase 2b trial. Lancet. 2023 Mar 11;401(10379):843-855. doi: 10.1016/S0140-6736(22)02644-7.

  PMID: 36906345 DERIVED

Related Links

• DHHS, FDA, CBER (US). Guidance for industry: Toxicity grading for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials

MeSH Terms

Conditions

Whooping Cough; Bordetella Infections; Gram-Negative Bacterial Infections; Respiratory Tract Infections; Infections; Respiratory Tract Diseases

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses

Results Point of Contact

• Title: Chief Medical Officer
• Organization: ILiAD Biotechnologies

contact@iliadbiotech.com

800-603-3525

Study Officials

• Mary B Manning, MD

  Rapid Medical Research Inc

  PRINCIPAL INVESTIGATOR

• Barbara Rizzardi, MD

  Advanced Clinical Research Services, LLC

  PRINCIPAL INVESTIGATOR

• Vicki Miller, MD

  DM Clinical Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2019
• First Posted: May 8, 2019
• Study Start: June 15, 2019
• Primary Completion: February 14, 2020
• Study Completion: June 24, 2020
• Last Updated: June 27, 2023
• Results First Posted: June 27, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)