A Phase 1 Ascending Dose Study to Assess the Safety and Immunogenicity of Adenovirus Anthrax Vector Candidate Vaccines

NCT01979406 | Completed Phase 1 DMC

• 1 other identifier: PXVX-PA-100-001
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate 2 vaccine candidates against anthrax compared to the positive (vaccine) control as studied in normal healthy volunteers.

Conditions

Anthrax Infection

Keywords

Anthrax vaccine

Outcome Measures

Primary Outcomes (1)

• The safety, tolerability and immunogenicity of the Ad4 PA and Ad4 PA GPI vaccines across a range of dosages and schedules.

  Safety will be measured by looking at safety labs, Adverse Events (AEs) and vaccine reactogenicity data from Baseline through Day 211. Immunogenicity will be measured by the peak serum antibody response to the PA transgene defined as the highest toxin-neutralizing antibody (TNA) titer achieved by a subject at any time between the first post-vaccination visit though Day 85 (and Day 211 if Day 85 is positive).

  Day 1 through Day 211

Secondary Outcomes (7)

• Antibody response of the Ad4-PA formulation to Ad4 PA GPI

  Day 1 through Day 85 (Day 211 if Day 85 is positive)

• Antibody response of the Ad4-PA and Ad4-PA-GPI vaccination regimens to the anticipated AVA PEP regimen.

  Days 1 through 85 (Day 211 if Day 85 is positive)

• Antibody response induced by 3 different dosages of Ad4 PA and Ad4 PA GPI.

  Days 1 through 85 (Day 211 if Day 85 is positive)

• TNA and antibody response induced by Ad4 PA and Ad4 PA GPI on 3 different vaccination schedules.

  Days 1 through 85 (Day 211 if Day 85 is positive)

• Pre-existing Ad4 immunity on TNA and PA-ELISA response induced by Ad4 PA and Ad4 PA GPI.

  Days 1 through 85 (Day 211 if Day 85 is positive)

Other Outcomes (2)

• Systemic PA-specific cellular immune response induced by Ad4-PA and Ad4-PA-GPI

  Days 1 through 43

• Mucosal PA-ELISA antibody responses induced by Ad4-PA and Ad4 PA-GPI

  Days 1 through 29

Study Arms (7)

AVA

ACTIVE COMPARATOR

Anthrax Vaccine Adsorbed (0.5 mL) as the placebo control on Days 1, 15 and 29

Biological: AVA

Ad4-PA-1

EXPERIMENTAL

Given at 10\^9, 10\^10 and 10\^11 vp Ad4-PA at Day 1 + oral placebo on Day 15 + AVA boost at Day 29

Biological: AVA; Biological: Ad4-PA-1

Ad4-PA-2

EXPERIMENTAL

Given at 10\^9, 10\^10 and 10\^11 vp Ad4-PA at Days 1, 15 and 29

Biological: Ad4-PA-1

Ad4-PA-3

EXPERIMENTAL

Ad4 given at 10\^9, 10\^10 and 10\^11 vp Ad4 PA-GPI at Day 1 + AVA boost at Day 15 + placebo on Day 29

Biological: AVA; Biological: Ad4-PA-1

Ad4-PA-GPI-1

EXPERIMENTAL

Given at 10\^9, 10\^10 and 10\^11 viral particles Ad4 PA-GPI at Day 1 + oral placebo on Day 29 + AVA boost at Day 15

Biological: AVA; Biological: Ad4-PA-GPI-1

Ad4 PA-GPI-2

EXPERIMENTAL

Given at 10\^9, 10\^10 and 10\^11 viral particles Ad4 PA-GPI at Day 1 + placebo on Day 15 + AVA boost at Day 29

Biological: AVA; Biological: Ad4-PA-GPI-1

Ad4-PA-GPI -3

EXPERIMENTAL

Given at 10\^9, 10\^10 and 10\^11 viral particles Ad4-PA-GPI at Days 1, 15 and 29

Biological: Ad4-PA-GPI-1

Interventions

AVA BIOLOGICAL

Anthrax Vaccine Adsorbed (0.5 mL) as the placebo control on Days 1, 15 and 29

Also known as: Anthrax vaccine adsorbed (BioThrax)

AVA; Ad4 PA-GPI-2; Ad4-PA-1; Ad4-PA-3; Ad4-PA-GPI-1

Ad4-PA-1 BIOLOGICAL

Ad4-PA will be given at 10\^9, 10\^10 and 10\^11 on Day, followed by an oral placebo on Day 15 and an AVA boost on Day 29

Also known as: Adenovirus serotype 4 vector vaccine against anthrax PA

Ad4-PA-1; Ad4-PA-2; Ad4-PA-3

Ad4-PA-GPI-1 BIOLOGICAL

Given at 10\^9, 10\^10 and 10\^11 viral particles Ad4 PA-GPI at Day 1 + oral placebo on Day 29 + AVA boost at Day 15

Also known as: Adenovirus anthrax vaccine serotype 4 against anthrax PA

Ad4 PA-GPI-2; Ad4-PA-GPI -3; Ad4-PA-GPI-1

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able to understand the study and give written informed consent.
• Healthy men or women aged 18-40 years old,
• BMI between 18 to 36 kg/m2
• Women of child bearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to vaccination on all vaccination days; they must also be willing to use adequate birth control for the duration of the study and have additional pregnancy tests if indicated.
• Intact upper arms with sufficient muscular tissue in the deltoid region for IM vaccine administration.
• Subject must be available for the study duration
• Subject must avoid strenuous exercise for at least 72 hours prior to each study vaccine administration.

You may not qualify if:

• Subject is a healthcare worker who has direct contact with patients or has an household contact (HHC) who is immunodeficient or HIV-positive, pregnant, has an unstable medical condition, or is under the age of 18.
• Subject is a childcare worker or a parent who has direct contact with children 5 years old and younger.
• Subject directly prepares food in the food industry.
• Pregnant or breastfeeding throughout the duration of the study until the final visit
• Military service between 1971 and 1999, or after 2012 when Ad4 vaccine was/is routinely given
• Employment in an industry involved in contact with ruminant animals, veterinary sciences, or other potential exposure to B. anthracis
• Received previous Ad4 vaccination or experimental Ad4 vector vaccines
• Received previous anthrax vaccine
• Received or plans to receive any other approved or investigational vaccines from 30 days prior to the first study vaccination until 30 days after the final study vaccination for live attenuated vaccines and from 15 days prior to the first study vaccination until 15 days after the final study vaccination for inactivated vaccines
• HIV or Hepatitis B or C positive
• Immunodeficient or has an unstable medical condition including psychiatric conditions
• Active or past history of acute or chronic gastrointestinal conditions
• Active or past history of cancer except basal cell carcinoma
• Recipient of bone marrow or solid organ transplant
• Received or plans to receive systemic antiviral medication, within 30 days prior to the first study vaccination

Sponsors & Collaborators

• Emergent BioSolutions: lead

Study Sites (4)

The Center for Pharmaceutical Research

Kansas City, Kansas, 64114, United States

Location

Walter Reed Army Institute for Research

Silver Spring, Maryland, 20910, United States

Location

St. Louis University

St Louis, Missouri, 63104, United States

Location

Coastal Carolina Research Center

Mt. Pleasant, South Carolina, 29464, United States

Location

MeSH Terms

Conditions

Anthrax

Interventions

Anthrax Vaccines; Biothrax

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Marc Gurwith, MD

  Emergent BioSolutions

  PRINCIPAL INVESTIGATOR

• Jakub Simon, MD

  Emergent BioSolutions

  STUDY DIRECTOR

• Mo Elsafy, MD, MSc

  National Institutes of Health (NIH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2013
• First Posted: November 8, 2013
• Study Start: November 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: September 1, 2015
• Last Updated: March 18, 2024

Record last verified: 2024-03

Locations

US (4)