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

NCT04148118 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: BW1010-001HHSN272201600045C16-0111
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Anthrax

Keywords

Anthrax; Nanoemulsion adjuvant; Nasal Vaccine; Recombinant Protective Antigen

Outcome Measures

Primary Outcomes (4)

• Safety Objectives: Frequency of solicited systemic and local reactions (reactogenicity and tolerability) reported after each immunization

  This will be conducted throughout the 2 hours in-clinic observation following each immunization, during the follow up Safety Phone Call conducted 1-3 days post immunization, during the review of the Symptom Diary Reminder Card that will be distributed to participants following immunization and during the 7 to 10 day visit following each immunization.

  Up to Day 39 scheduled visit.

• Safety Objectives: Frequency of Adverse Events (AE)

  All treatment-emergent AEs will be summarized. These are AEs beginning or worsening after the initiation of the first immunization. These including any clinical laboratory abnormalities.

  Up to Day 85 scheduled visit.

• Safety Objectives: Frequency of Serious Adverse Events (SAEs)

  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 scheduled visit.

• Primary Immunogenicity Objectives: Assess and compare the increase in rPA neutralizing antibodies following the different interventions in Cohort 2 subjects.

  Use serum Toxin Neutralizing Assay (TNA) to compare immune response in the rPA 100 µg dose between the two different methods of administration (Aptar Bidose sprayer and Eppendorf Electronic Repeater pipette) of BW-1010 and compare them with the positive control arm receiving BioThrax.

  Day 57 and Day 85 (co-primary end point). The two time points will be compared to identify the optimum timing of peak immuneresponse following nasal vaccination.

Secondary Outcomes (1)

• Secondary Immunogenicity Objectives: Assess and compare the increase in anti-rPA antibodies following the different interventions in Cohort 2 subjects.

  Day 57 and Day 85.

Other Outcomes (3)

• Exploratory Immunogenicity Objectives: Assess and compare the increase in rPA neutralizing and anti-rPA antibodies following the different interventions in Cohort 2 subjects.

  Baseline, Days 39, 197 and 393.

• Exploratory Immunogenicity Objectives: Assess and compare the increase in mucosal antibodies following different interventions in Cohort 2 subjects.

  Baseline and Day 39.

• Exploratory Immunogenicity Objectives: Assess and compare the increase in cell meditated immune responses in PBMCs following different interventions in Cohort 2 subjects.

  Baseline and Day 39.

Study Arms (7)

NE+50µg rPA - sprayer

EXPERIMENTAL

Biological: BW-1010: 50 µg - sprayer - IN

NE+50µg rPA - pipette

EXPERIMENTAL

Biological: BW-1010: 50 µg - pipette - IN

NE+100µg rPA - sprayer

EXPERIMENTAL

Biological: BW-1010: 100 µg - sprayer - IN

NE+100µg rPA - pipette

EXPERIMENTAL

Biological: BW-1010: 100 µg - pipette - IN

Saline - sprayer

PLACEBO COMPARATOR

Biological: Saline (Placebo) - sprayer - IN

Saline - pipette

PLACEBO COMPARATOR

Biological: Saline (Placebo) - pipette - IN

BioThrax - SC

ACTIVE COMPARATOR

Biological: BioThrax (positive control) - SC

Interventions

BW-1010: 50 µg - sprayer - IN BIOLOGICAL

20% Nanoemulsion and 50 µg recombinant protective antigen administered intranasally by Aptar Bidose Sprayer (400µL). Two doses administered 4 weeks apart.

NE+50µg rPA - sprayer

BW-1010: 50 µg - pipette - IN BIOLOGICAL

20% Nanoemulsion and 50 µg recombinant protective antigen administered intranasally by pipette (400µL). Two doses administered 4 weeks apart.

NE+50µg rPA - pipette

BW-1010: 100 µg - sprayer - IN BIOLOGICAL

20% Nanoemulsion and 100 µg recombinant protective antigen administered intranasally by Aptar Bidose Sprayer (400µL) Two doses administered 4 weeks apart

NE+100µg rPA - sprayer

BW-1010: 100 µg - pipette - IN BIOLOGICAL

20% Nanoemulsion and 100 µg recombinant protective antigen administered intranasally by pipette (400µL). Two doses administered 4 weeks apart.

NE+100µg rPA - pipette

Saline (Placebo) - sprayer - IN BIOLOGICAL

Saline (negative control) administered intranasally by Aptar Bidose Sprayer (400µL). Two doses administered 4 weeks apart.

Saline - sprayer

Saline (Placebo) - pipette - IN BIOLOGICAL

Saline (negative control) administered intranasally by pipette (400µL). Two doses administered 4 weeks apart.

Saline - pipette

BioThrax (positive control) - SC BIOLOGICAL

BioThrax licensed vaccine administered subcutaneously (500µL). Three doses administered 2 weeks apart.

BioThrax - SC

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Between 18 to 49 years of age, inclusive.
• Female of child-bearing potential, must be non-lactating and non-pregnant as confirmed by a negative serum pregnancy test conducted at screening and a negative urine pregnancy test conducted at the site within 24 hours preceding each receipt of vaccine.
• Females should be either:
• Surgically sterile. Surgical sterilization includes hysterectomy, bilateral salpingectomy, tubal ligation or successful other permanent sterilization methods such as Essure® placement with documented confirmation test at least 3 months after the procedure, or
• At least one year post-menopausal, or
• Agree to use highly effective hormonal contraceptive method defined by a \<1% failure rate that is not affected by adherence such as progestin releasing subdermal implants, or levonorgestrel releasing IUDs, for a minimum of 30 days prior to immunization and for 3 months following the last immunization. Concurrent use of a barrier method of birth control is not required. or
• If using a moderately effective contraceptive method defined by a 5-9% failure rate per year with typical use, such as the pill, hormone releasing transdermal patch or ring, or Progestin-only Injectable Contraceptive (DMPA) injections. Concurrent use of a barrier method of contraception is required. or
• Have acceptable sexual abstinence as defined by refraining from heterosexual intercourse for a minimum of 30 days prior to immunization and a credible intent to continue to do so until 3 months following the last immunization. The reliability of sexual abstinence will be to be evaluated in relation to the preferred and usual lifestyle of the subject.
• Males must agree to use condoms from screening through 3 months following the last immunization, unless vasectomized.
• Males must not donate sperm from screening through 3 months following the last immunization.
• Are healthy, as determined by medical history, physical examination, vital signs, and clinical laboratory examinations. Healthy participants have no chronic medical conditions and no acute medical conditions that required the use of systemic prescription medications in the last 30 days or 5 half-lives, whichever is longer.
• Comprehends the study requirements, is available for the required study period, and is able to attend scheduled visits.
• Has given written informed consent to participate in the study.

You may not qualify if:

• Presence of significant acute illness or any chronic medical condition.
• Presence of psychiatric illness, currently untreated or clinically unstable (in the opinion of the PI) schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with participant compliance or safety evaluations.
• Participants with a history of chronic cough, reactive airway disease, asthma, chronic obstructive pulmonary disease (COPD), frequent sinus infections, sinusitis, allergic rhinitis, nasal polyps or obstruction, including deviated septum or other major nasopharyngeal anatomic abnormalities significant enough to obstruct the nasal openings, are to be excluded. Participants with seasonal rhinitis may be included if their 'season' does not occur within 3 months of the immunization date and they are not currently receiving intranasal steroids.
• History of natural anthrax infection.
• Receipt of any licensed or experimental anthrax vaccine at any time in the participant's lifetime.
• The participant or an immediate household member is meeting criteria for which receipt of licensed anthrax vaccine is recommended or expected including:
• Exposure to animal products such as hides, hair, or bones which come from anthrax endemic areas and may be contaminated with Bacillus anthracis spores.
• Engagement in diagnostic or investigational activities which may result in contact with B. anthracis spores.
• Holding of a position such as veterinarians and others handling potentially infected animals.
• Military personnel for whom immunization with anthrax vaccine is required.
• Positive serology for HIV-1 or HIV-2, or HCV antibodies.
• Platelet count \<150,000/mm3.
• History of aspiration, dysphagia, swallowing disorders, stroke or other neurologic conditions that may predispose the participant to aspiration of test articles into the respiratory tract.
• History of Bell's palsy.
• Cancer or treatment for cancer, within 3 years. Participants with a history of cancer who are disease-free without treatment for 3 years or more are eligible. Participants with basal cell carcinoma or squamous cell carcinoma are allowed, unless present on or near the nose.

Sponsors & Collaborators

• BlueWillow Biologics: lead
• Porton Biopharma Ltd.: collaborator

Study Sites (1)

Johnson County Clin-Trial

Lenexa, Kansas, 66219, United States

Location

MeSH Terms

Conditions

Anthrax

Interventions

Sodium Chloride; Biothrax

Condition Hierarchy (Ancestors)

Bacillaceae Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study participants and the study site personnel managing the participants will be blinded to the identity of the test article. The pharmacist and/or the pharmacy technician or non-study nurse at the study site will not be blinded and will be responsible for preparing, labeling, and administering the investigational product. During study drug administration, all the blinded personnel will be excluded from the vaccine administration site. In addition, participants will be asked to close their eyes or be offered the option of wearing a loose-fitting eye mask during the administration of the test article. Participants in the study arm that receive BioThrax SC and the clinical trial personnel that are managing them will not be blinded for this arm due to the different route of administration that makes blinding impossible. For laboratory and immunological testing, samples from participants receiving BioThrax will be blinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 28, 2019
• First Posted: November 1, 2019
• Study Start: January 8, 2020
• Primary Completion: September 2, 2021
• Study Completion: September 2, 2021
• Last Updated: May 18, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)