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

Pertussis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03942406
• Other study ID #: IB-200P
• Status: Completed
• Phase: Phase 2
• Start date: June 15, 2019
• Est. completion date: June 24, 2020

Study information

• Verified date: May 2023
• Source: ILiAD Biotechnologies
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: June 24, 2020
• Est. primary completion date: February 14, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pertussis
• Whooping Cough

Intervention

Combination Product:
• BPZE1 pertussis vaccine and VaxINator(TM) Atomization Device
Live attenuated pertussis vaccine administered via the VaxINator(TM) atomization device

Locations

Country	Name	City	State
United States	Rapid medical Research Inc	Cleveland	Ohio
United States	DM Clinical Research	Tomball	Texas
United States	Advanced Clinical Research	West Jordan	Utah

Sponsors (2)

Lead Sponsor	Collaborator
ILiAD Biotechnologies	PPD

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Systemic Immunogenicity - Summary of Systemic IgG Seroconversion Endpoints	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
Secondary	Systemic Immunogenicity - Summary of Systemic IgA Seroconversion Endpoints	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
Secondary	Systemic Immunogenicity - Summary of Geometric Mean Fold Rises (GMFRs) of Systemic IgG Against Whole Cell Extract by Vaccine Group and Time Point	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
Secondary	Systemic Immunogenicity - Summary of GMFRs of Systemic IgG Against Whole Cell Extract by Vaccine Group and Time Point	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
Secondary	Mucosal Immunogenicity - Summary of Mucosal Absolute S-IgA/Total S-IgA Seroconversion Endpoints	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
Secondary	Mucosal Immunogenicity - Summary of GMFRs of Mucosal Absolute S-IgA/Total S-IgA Against Whole Cell Extract by Vaccine Group and Time Point	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
Secondary	Mucosal Immunogenicity - Summary of GMFRs of Mucosal Absolute S-IgA/Total S-IgA Against Whole Cell Extract by Vaccine Group and Time Point	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
Secondary	Colonization - Summary of Colonization for B. Pertussis Bacterial Culture From Nasal Sample by Timepoint	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
Secondary	Safety - Number of Participants With Unsolicited AEs	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
Secondary	Safety - Number of Participants With Unsolicited AEs	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
Secondary	Safety - Number of Participants With Serious AEs	Number of participants with Serious AEs collected on Day 1 through Day 84 by MedDRA classification.	Days 1 to 84
Secondary	Safety - Number of Participants With Serious AEs	Number of participants with Serious AEs collected on Day 85 through Day 113 by MedDRA classification.	Days 85 to 113
Secondary	Safety - Number of Participants With Serious AEs	Number of participants with Serious AEs collected on Day 114 through Day 254 by MedDRA classification.	Days 114 to 254 (end of study)

External Links

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