A Safety and Immunogenicity of Intranasal Nanoemulsion Adjuvanted Recombinant Pandemic Flu Vaccine in Healthy Adults

NCT05397119 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: BW-1014-001U01AI14808120-0036
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical trial is to evaluate the safety and immunogenicity of BW-1014. BW-1014 is a nanoemulsion (NE) adjuvanted recombinant Hemagglutinin 5 (rH5) that would protect against pandemic flu. The study will be conducted in 40 healthy adults volunteers, age 18 - 45, in one center in the United States. The study will compare 3 different dose levels of rH5 (25µg, 50µg and 100µg rH5 in 20% NE adjuvant using a pipette dropper with rH5 control (100µg without NE adjuvant) and placebo control (saline). The investigational product will be administered in 2 doses intranasally (IN). This will be followed 6 months later with a licensed H5N1 IIV IM vaccine. In addition to safety outcome, homologous and heterologous immunological outcomes will be tested in nasal wash, serum, and blood cells.

Conditions

Influenza, Pandemic

Keywords

Pandemic influenza; Nanoemulsion adjuvant; Nasal vaccine; rH5

Outcome Measures

Primary Outcomes (8)

• Safety Outcome: Number of participants reporting local or systemic reactions

  Local and systemic reactions will be assessed in the clinic within 1 hour of intranasal BW-1014, positive control, and placebo administration, including visual assessment of nasal passages

  Up to Day 29

• Safety Outcome: Number of participants reporting solicited reactions and general AEs

  Solicited reactions and general AEs will be assessed in follow up visit/phone call within 7 days of vaccination with intranasal BW-1014, positive control and placebo

  Up to Day 36

• Safety Objective: Number of participants reporting unsolicited AEs

  Unsolicited AEs will be assessed in follow up visits/phone calls within 28 days of primary vaccinations with intranasal BW-1014, positive control and placebo

  Up to Day 57

• Safety Outcome: Number of participants reporting any hematological and biochemical laboratory abnormality (Class 1 of higher)

  Hematological and biochemical laboratory abnormality (Class 1 of higher) will be assessed in follow up visits within 7 days of first dose intranasal BW-1014 or within 14 days second dose intranasal BW-1014, positive control, and placebo

  Up to Day 43

• Safety Outcome: Number of participants reporting medically attended AEs (MAAEs)

  MAAEs will be assessed in follow up visits/phone calls within 28 days of primary vaccinations with intranasal BW-1014, positive control, and placebo

  Up to Day 57

• Safety Outcome: Number of participants reporting serious adverse events (SAEs)

  SAEs will be assessed by study arm. An adverse event is considered "serious" if it results in death, or a life-threatening AE, or in hospitalization, or in a substantial disruption of the ability to conduct normal life functions, or in a congenital anomaly/birth defect.

  Up to Day 393

• Safety Outcome: Number of participants reporting potential immune-mediated medical conditions (PIMMCs)

  PIMMCs will be assessed by follow up visits/phone calls following vaccinations with intranasal BW-1014, positive control, and placebo

  Up to Day 393

• Safety Outcome: Number of participants reporting new onset chronic medical conditions (NOCMCs)

  NOCMCs will be assessed by follow up visits/phone calls following vaccinations with intranasal BW-1014, positive control, and placebo

  Up to Day 393

Secondary Outcomes (23)

• Safety endpoint: Number of participants reporting local or systemic reactions to intramuscular H5N1 IIV vaccine

  Day 197

• Safety endpoint: Number of participants reporting solicited reactions and general AEs

  Day 204

• Safety endpoint: Number of participants reporting unsolicited AEs

  Day 225

• Safety endpoint: Number of participants reporting any hematological and biochemical laboratory abnormality (Class 1 of higher)

  Day 204

• Safety endpoint: Number of participants reporting medically attended AEs (MAAEs)

  Day 225

Study Arms (5)

BW-1014: 25 µg rH5 in 20% NE - pipette - IN

EXPERIMENTAL

20% Nanoemulsion and 25 µg recombinant H5 antigen administered intranasally by an electronic pipette (500µL) Two doses administered 4 weeks apart

Biological: BW-1014: 25 µg rH5 in 20% NE - pipette - IN; Biological: H5N1 IIV - IM

BW-1014: 50 µg rH5 in 20% NE - pipette - IN

EXPERIMENTAL

20% Nanoemulsion and 50 µg recombinant H5 antigen administered intranasally by an electronic pipette (500µL) Two doses administered 4 weeks apart

Biological: BW-1014: 50 µg rH5 in 20% NE - pipette - IN; Biological: H5N1 IIV - IM

BW-1014: 100 µg rH5 in 20% NE - pipette - IN

EXPERIMENTAL

20% Nanoemulsion and 100 µg recombinant H5 antigen administered intranasally by an electronic pipette (500µL) Two doses administered 4 weeks apart

Biological: BW-1014: 100 µg rH5 in 20% NE - pipette - IN; Biological: H5N1 IIV - IM

rH5 (100 µg) control - pipette - IN

PLACEBO COMPARATOR

100 µg recombinant H5 antigen (without adjuvant) administered intranasally by an electronic pipette (500µL) Two doses administered 4 weeks apart

Biological: rH5 (100 µg) control - pipette - IN; Biological: H5N1 IIV - IM

Saline (Placebo) - pipette - IN

SHAM COMPARATOR

Saline (negative control) administered intranasally by an electronic pipette (500µL) Two doses administered 4 weeks apart

Biological: Saline (Placebo) - pipette - IN; Biological: H5N1 IIV - IM

Interventions

BW-1014: 25 µg rH5 in 20% NE - pipette - IN BIOLOGICAL

20% Nanoemulsion and 25 µg recombinant H5 antigen administered intranasally by an electronic pipette (500µL) Two doses administered 4 weeks apart

BW-1014: 25 µg rH5 in 20% NE - pipette - IN

BW-1014: 50 µg rH5 in 20% NE - pipette - IN BIOLOGICAL

20% Nanoemulsion and 50 µg recombinant H5 antigen administered intranasally by an electronic pipette (500µL) Two doses administered 4 weeks apart

BW-1014: 50 µg rH5 in 20% NE - pipette - IN

BW-1014: 100 µg rH5 in 20% NE - pipette - IN BIOLOGICAL

20% Nanoemulsion and 100 µg recombinant H5 antigen administered intranasally by an electronic pipette (500µL) Two doses administered 4 weeks apart

BW-1014: 100 µg rH5 in 20% NE - pipette - IN

rH5 (100 µg) control - pipette - IN BIOLOGICAL

100 µg recombinant H5 antigen (without adjuvant) administered intranasally by an electronic pipette (500µL) Two doses administered 4 weeks apart

rH5 (100 µg) control - pipette - IN

Saline (Placebo) - pipette - IN BIOLOGICAL

Saline (negative control) administered intranasally by an electronic pipette (500µL) Two doses administered 4 weeks apart

Saline (Placebo) - pipette - IN

H5N1 IIV - IM BIOLOGICAL

90 µg H5N1 IIV administered intramuscularly (1 mL) One booster dose administered 6 months following last immunization

BW-1014: 100 µg rH5 in 20% NE - pipette - IN; BW-1014: 25 µg rH5 in 20% NE - pipette - IN; BW-1014: 50 µg rH5 in 20% NE - pipette - IN; Saline (Placebo) - pipette - IN; rH5 (100 µg) control - pipette - IN

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy men or women aged 18 through 45 years of age, inclusive.
• Women must not be pregnant or nursing. If premenopausal, absence of pregnancy must be confirmed by a negative serum pregnancy test conducted at screening and a negative urine pregnancy test conducted at the site within 24 hours preceding receipt of vaccine.
• Women who are not surgically sterile or at least one year post-menopausal must agree to use acceptable birth control. Acceptable birth control methods include oral, implantable, transdermal or injectable contraceptive; barrier methods such as condoms, cervical caps, or diaphragms with spermicide; abstinence from sexual relationships with a male partner, non-male sexual relationships, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving the first study vaccination, and other reliable forms of contraception approved by the Investigator. Acceptable birth control must be used for a minimum of 30 days prior to vaccination and for 3 months following final study vaccination.
• Subjects must be able to comprehend the study requirements as evidenced by a score of ≥ 70% on the comprehension assessment (two attempts permitted), be available for the required study period, and have the ability to attend scheduled visits.
• Subjects must be able to provide written informed consent to participate in the study.
• Subject agrees to future use of left-over specimens and to the collection of additional specimens for potential future use research.
• Receipt of the CDC-recommended number of doses of an EUA authorized or licensed COVID-19 vaccine product ≥ four weeks prior to first study vaccination.

You may not qualify if:

• Presence of significant acute or chronic, uncontrolled medical or psychiatric illness (institution of new medical or surgical treatment, or a significant dose alteration for uncontrolled symptoms or drug toxicity within 3 months). This includes signs or symptoms consistent with upper or lower respiratory tract infections.
• Participants with symptoms of COVID-19 and/or who are positive for SARS-CoV-2 by molecular testing conducted within 2 days prevaccination.
• Have known hypersensitivity or allergy to eggs, egg or chicken protein, or other components of the Influenza Virus Vaccine, H5N1 (Sanofi Pasteur).
• Receipt of licensed or experimental H5N1 influenza vaccine ever.
• Subjects with a history of chronic cough, frequent sinus infections, sinusitis, allergic rhinitis, nasal polyps or obstruction, including deviated septum significant enough to obstruct the nasal openings or a history of nasal surgery.
• Body mass index (BMI) BMI ≤ 18.5 or ≥ 40.
• Positive serology for human immunodeficiency virus (HIV)-1 or HIV-2, hepatitis B, or hepatitis C (HCV).
• Platelet count less than 100,000/mm prior to randomization during baseline visit.
• History of drug or chemical abuse within the past year prior to screening.
• History of aspiration, dysphagia, swallowing disorders, stroke or other neurologic conditions that may predispose the subject to aspiration of test articles into the respiratory tract.
• History of Bell's palsy.
• History of Guillain-Barré syndrome within 6 weeks of prior influenza virus vaccine.
• Cancer or treatment for cancer, within 3 years. Basal cell carcinoma or squamous cell carcinoma are allowed, unless present on or near the nose.
• Impaired immune responsiveness, including a history of diabetes mellitus.
• Chronic use of inhaled or intranasal sprays including decongestants and corticosteroids.

Sponsors & Collaborators

• BlueWillow Biologics: lead
• University of Maryland, Baltimore: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Center for Vaccine Development and Global Health, University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

Related Publications (1)

• Deming ME, Toapanta FR, Pasetti M, Golding H, Khurana S, Hamouda T, Fattom A, Liang Y, Tennant SM, McGilvray MF, Bernal PJ, Oshinsky JJ, Datta S, Booth JP, Coughlan L, Neuzil KM, Costley CD, Kotloff KL, Sztein MB, Ortiz JR; rH5 Writing Group. An intranasal adjuvanted, recombinant influenza A/H5 vaccine primes against diverse H5N1 clades: a phase I trial. Nat Commun. 2025 Nov 6;16(1):9321. doi: 10.1038/s41467-025-64686-3.

  PMID: 41198655 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Justin Ortiz, MD, MS

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All IN study vaccines are milky white in appearance. Vaccinators will be unblinded to vaccine allocation, but they will have no role in assessment of vaccine safety or immunogenicity. Only the vaccine compounding personnel, the unblinded vaccinator, and the study statistician will have access to the randomization code prior to study completion. Unblinding procedures are described in the Manual of Operations.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to receive BW-1014 in 3 different dose levels (25 µg, 50 µg or 100 µg rH5 in NE adjuvant), using a pipette dropper. Control arms include rH5 alone (without NE adjuvant) or placebo (saline) control. Since this is first in humans, a dose escalation assessment will take place. A sentinel group of 2 participants from the lowest dose (25 µg rH5 in NE) with 2 rH5 control and 2 placebo control will be dosed first before proceeding to the next dose level. Each escalation of dose will take place after safety clearance of the prior lower dose level. Dosing of the remainder of subjects per dose arm will take place after safety clearance of the corresponding dose sentinel participants.

Study Record Dates

• First Submitted: May 13, 2022
• First Posted: May 31, 2022
• Study Start: July 7, 2022
• Primary Completion: October 12, 2023
• Study Completion: October 12, 2023
• Last Updated: August 22, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)