A Safety and Immunogenicity of Intranasal Nanoemulsion Adjuvanted Recombinant Anthrax Vaccine in Healthy Adults
Condition: Anthrax
MeSH terms: Anthrax
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this clinical trial is to evaluate the safety and immunogenicity of BW-1010.

      BW-1010 is a nanoemulsion adjuvanted recombinant protein (rPA) that would protect against
      fatal outcome resulting from exposure to anthrax.

      The vaccine will be administered intranasally (IN) to healthy adults, age 18 - 49.

      The study will be conducted in 84 volunteers in one center in the United States.

      The study will compare 2 different dose levels of rPA (50µg and 100µg rPA), and 2 different
      administration methods (a sprayer and dropper) with a negative control (saline) and a
      positive control (the injectable BioThrax licensed vaccine).

      The vaccines and negative controls will be administered in 2 IN doses (4 weeks apart). The
      positive control will be 3 subcutaneous doses, 2 weeks apart. All volunteers will be observed
      for 1 year after the last dose.

      Immunological outcome studied will be from the serum, blood cells and nasal washes.
    

Detailed description: 
      This study is a single center, randomized, observer-blind, active- and placebo-controlled,
      dose comparison study to assess the safety, tolerability and immunogenicity of BW-1010
      administered IN using an Aptar Bidose sprayer or an Eppendorf Electronic Repeater pipette in
      healthy adult volunteers. There is an additional unblinded BioThrax arm administered by SC
      injection. BioThrax is included in the study design only to provide a licensed, active
      control for immunogenicity and safety comparisons. A total of 84 participants will be
      enrolled in the study. Participants will be randomized in one of the following 7 arms:

      A) BW-1010: 50µg - sprayer - IN, 400 µL; 16 participants.

      B) BW-1010: 50µg - pipette - IN, 400 µL; 16 participants.

      C) BW-1010: 100µg - sprayer - IN, 400 µL; 16 participants.

      D) BW-1010: 100µg - pipette - IN, 400 µL; 16 participants.

      E) Saline (Placebo) - sprayer - IN, 400 µL; 6 participants.

      F) Saline (Placebo) - pipette - IN, 400 µL; 6 participants.

      G) BioThrax (Positive control) - SC, 500 µL; 8 participants.

      All participants receiving test article or placebo will receive two doses of the vaccine four
      weeks apart. Each of these participants will receive treatment intranasally using either an
      Aptar Bidose sprayer or an Eppendorf Electronic Repeater pipette. Eight participants will be
      randomized to receive a positive control (BioThrax vaccine) and will receive 3 doses of
      vaccine two weeks apart.

      Since this is the first-in-human study for BW-1010, a total of twelve sentinel participants
      will receive either the test article or the placebo in a randomized fashion prior to dosing
      the main participants. Four of the 50 µg rPA vaccine and two placebo control participants
      will be randomized and dosed first, with no more than one participant/day with at least 24
      hours safety follow up prior to enrolling the next participant. The Safety Review Committee
      (SRC) will review all safety data available through the Day 8 visit of the last sentinel
      participant dosed from this group and provide clearance to proceed with the 50 µg rPA Main
      Study participants and the 100 µg sentinel group. Four of the 100 µg rPA vaccine Sentinel
      Group and two placebo control participants will be randomized and dosed after safety
      clearance of the 50 µg rPA sentinel group, with no more than one participant/day with at
      least 24 hours safety follow up prior to enrolling the next participant. The SRC will review
      all safety data available through the Day 8 visit of the last sentinel participant dosed from
      this group and provide clearance to proceed with the 100 µg rPA Main Study participants.

      Participants will be followed up for safety and tolerability for 1 year following last
      immunization.

      Participants will be assessed for production of specific antibodies in the form of serum
      toxin neutralization antibodies (TNA) and serum anti-rPA IgG throughout the study until the
      termination visit.

      Since this is a nasal vaccine and it is anticipated that the immune response will be
      different that the standard parental vaccines, the participants will be tested 10 days post
      last dose for rPA-specific cytokine on T-cells (IFN-ɤ, IL-5 and IL-17) and rPA-specific IgG
      and Ig-A on B-cells. Nasal wash will also be tested for total IgA and rPA-specific IgG and
      IgA.

      Safety and immunogenicity analysis will include all randomized participants. Analysis will
      compare the different dose levels, different method of administration. Participants who
      received BW-1010 will be compared to participants who received the saline negative control
      and the BioThrax positive control.

      COVID-19 Shut Down Impact on the Clinical Trial:

      After the majority of the 50µg subjects had received only 1 of the 2 planned immunization,
      the Covid-19 pandemic stay-at-home order was instated and they could not receive their 2nd
      immunization. As a result of this, after COVID shut down was released, subjects involved in
      the clinical trial were divided into 2 Cohorts:

        1. Cohort 1: Subjects from the Sentinel and 50µg main groups who received 2 or 1
           immunizations prior to COVID-19 stay-at-home restrictions. Except for COVID-interrupted
           visits, these subjects will continue safety assessment at their their originally planned
           visits. Due to incomplete immunization schedule, no immunological testing will be
           performed.

        2. Cohort 2: These are the subjects who were not enrolled prior to the Covid-19 impacts. In
           order to maintain enough power to detect critical safety issues in the clinical trial,
           these remaining 43 subjects will be randomized to receive the 100 µg rPA dose or placebo
           (either by pipette or sprayer) or BioThrax. No additional 50 µg rPA subjects will be
           dosed. These 43 subjects will follow the original study plan:

             1. Immunization at Week 0 and Week 4 (+ Week 2 for BioThrax).

             2. Follow up on Weeks 1, 5.5, 8, 12, 28 and 56 for safety and immunogenicity.
    

Intervention name(s): BW-1010: 50 µg - sprayer - IN; BW-1010: 50 µg - pipette - IN; BW-1010: 100 µg - sprayer - IN; BW-1010: 100 µg - pipette - IN; Saline (Placebo) - sprayer - IN; Saline (Placebo) - pipette - IN; BioThrax (positive control) - SC
Intervention type(s): Biological; Biological; Biological; Biological; Biological; Biological; Biological
Intervention description(s): 20% Nanoemulsion and 50 µg recombinant protective antigen administered intranasally by Aptar Bidose Sprayer (400µL).
Two doses administered 4 weeks apart.; 20% Nanoemulsion and 50 µg recombinant protective antigen administered intranasally by pipette (400µL).
Two doses administered 4 weeks apart.; 20% Nanoemulsion and 100 µg recombinant protective antigen administered intranasally by Aptar Bidose Sprayer (400µL)
Two doses administered 4 weeks apart; 20% Nanoemulsion and 100 µg recombinant protective antigen administered intranasally by pipette (400µL).
Two doses administered 4 weeks apart.; Saline (negative control) administered intranasally by Aptar Bidose Sprayer (400µL).
Two doses administered 4 weeks apart.; Saline (negative control) administered intranasally by pipette (400µL).
Two doses administered 4 weeks apart.; BioThrax licensed vaccine administered subcutaneously (500µL).
Three doses administered 2 weeks apart.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be randomized to receive BW-1010 in 2 different dose levels (50 µg or 100 µg rPA), using 2 different method of administration (Aptar sprayer or pipette dropper). Negative control participants (Placebo) will receive saline using the 2 different methods as well. The positive control participants will receive BioThrax subcutaneously.
Since this is first in humans, a sentinel group, 4 participants with the smaller dose level (50 µg rPA) and 2 placebos, will be dosed first. The main group of the 50 µg rPA and the higher level rPA sentinels will dosed after day 8 safety clearance of the low dose rPA sentinel participants.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Anthrax; Nanoemulsion adjuvant; Nasal Vaccine; Recombinant Protective Antigen