A Safety and Immunogenicity of Intranasal Nanoemulsion Adjuvanted Recombinant Anthrax Vaccine in Healthy Adults — IN NE-rPA  

Anthrax Clinical Trial

Official title: A Phase 1 Randomized, Observer-Blind, Active- and Placebo-Controlled Dose Comparison, Safety, Tolerability and Immunogenicity Study of Intranasal Adjuvanted Anthrax Vaccine (BW-1010; rPA + 20%W805EC) in Healthy Adult Volunteers Administered by Nasal Sprayer and Pipette With an Additional Unblinded Positive Control Arm

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Anthrax

• NCT number: NCT04148118
• Study type: Interventional
• Source: BlueWillow Biologics
• Status: Completed
• Phase: Phase 1
• Start date: January 8, 2020
• Completion date: September 2, 2021