Immunogenicity and Safety Study of a Three-Dose BioThrax® Regimen for Post-Exposure Prophylaxis in Healthy Adults

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Emergent BioSolutions
ClinicalTrials.gov Identifier:
NCT01491607
First received: December 12, 2011
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

The purpose of this Phase 3 clinical trial is to evaluate the immunogenicity and safety of BioThrax anthrax vaccine in healthy adults following 3 doses of BioThrax. Results of this study will be used to support a post-exposure prophylaxis (PEP) indication for BioThrax.

This study will be conducted in the United States (U.S.), in 200 healthy male and female volunteer subjects ages 18 to 65 years.

The duration of study participation for each individual subject will be approximately 128 days (4.25 months), including a screening period of approximately 28 days followed by 100 days on study.


Condition Intervention Phase
Anthrax
Biological: BioThrax
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Immunogenicity and Safety Study of a Three-Dose BioThrax® Regimen for Post-Exposure Prophylaxis in Healthy Adults

Resource links provided by NLM:


Further study details as provided by Emergent BioSolutions:

Primary Outcome Measures:
  • Percentage of Subjects Achieving a TNA Response of a Predefined Threshold Value at Day 63 (5 Weeks Following the Third Vaccination on Day 28). [ Time Frame: Day 63 +/- 2 days ] [ Designated as safety issue: No ]
    Neutralizing antibody levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50), which is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum.


Secondary Outcome Measures:
  • Percentage of Subjects Achieving a TNA Response of a Predefined Threshold Value at Day 70. [ Time Frame: Day 70 +/- 2 days ] [ Designated as safety issue: No ]
    Neutralizing antibody levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50), which is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum.

  • Average Percentage of Subjects Achieving a TNA Response of a Predefined Threshold Value Between Days 63 and 100 (Inclusive). [ Time Frame: Days 63 to 100 ] [ Designated as safety issue: No ]
    Neutralizing antibody levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50), which is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum.

  • Incidence of Injection Site Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards [ Time Frame: Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). ] [ Designated as safety issue: Yes ]
    Injection site reactions (warmth, tenderness, itching, pain, arm motion limitation, redness, lump, swelling, and bruise) were evaluated by using a web-enabled subject diary. Subjects assessed the severity of warmth, tenderness, itching, pain, arm motion limitation, lump, and bruise as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of redness and swelling were based on the diameter of the affected area. Severe injection site reactions were recorded as adverse events by the investigator site staff after confirmation with the subject.

  • Percentage of Injection Site Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards [ Time Frame: Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). ] [ Designated as safety issue: Yes ]
    Injection site reactions (warmth, tenderness, itching, pain, arm motion limitation, redness, lump, swelling, and bruise) were evaluated by using a web-enabled subject diary. Subjects assessed the severity of warmth, tenderness, itching, pain, arm motion limitation, lump, and bruise as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of redness and swelling were based on the diameter of the affected area. Severe injection site reactions were recorded as adverse events by the investigator site staff after confirmation with the subject.

  • Incidence of Systemic Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards [ Time Frame: Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). ] [ Designated as safety issue: Yes ]
    Systemic reactions (fatigue/ tiredness, muscle ache, headache, and fever) were evaluated by using a web-enabled subject diary. Subjects assessed severity as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of fever was assessed using a grading scale. Severe systemic reactions were to be recorded as adverse events by the investigator site staff after confirmation with the subject.

  • Percentage of Systemic Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards [ Time Frame: Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). ] [ Designated as safety issue: Yes ]
    Systemic reactions (fatigue/ tiredness, muscle ache, headache, and fever) were evaluated by using a web-enabled subject diary. Subjects assessed severity as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of fever was assessed using a grading scale. Severe systemic reactions were to be recorded as adverse events by the investigator site staff after confirmation with the subject.


Enrollment: 200
Study Start Date: November 2011
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BioThrax (0.5 mL, on days 0, 14, and 28) Biological: BioThrax
BioThrax, 0.5 mL administered subcutaneously on days 0, 14, and 28.
Other Name: Anthrax Vaccine Adsorbed (AVA)

Detailed Description:

BioThrax® (also called Anthrax Vaccine Adsorbed or AVA) is the only FDA-licensed vaccine for the prevention of anthrax infection. This study will evaluate the immunogenicity of the vaccine using a post-exposure vaccination schedule. Correlations will be drawn to immunogenicity and survival data from animal models to demonstrate that BioThrax® can elicit a protective immune response for PEP.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Be between 18 and 65 years of age, inclusive, at the time of enrollment.
  • Be in good health as determined by the investigator from medical history and a physical examination.
  • If a pre-menopausal female, must be using acceptable methods of birth control.
  • Have all hematology and chemistry parameters (measured at Screening) within the laboratory's normal range.
  • Be willing and able to return for all visits and blood collections for the duration of the study.
  • Have read, understood and signed an informed consent form.

Exclusion Criteria:

  • Prior immunization with anthrax vaccine or known exposure to anthrax organisms.
  • Intend to enlist in the military during the study.
  • Have a known allergy to aluminum hydroxide, formaldehyde, benzethonium chloride, or latex.
  • Plan to receive experimental products at any time during the study.
  • Have received a live vaccine in the 30 days before study entry.
  • Plan to receive a live vaccine at any time during the study.
  • Have ongoing drug abuse/dependence (including alcohol) issues and/or test positive in a urine drug screen for amphetamines, barbiturates, cocaine or opiates;
  • Have received immunosuppressive therapy (including systemic steroids) within 3 months prior to study entry.
  • Have a condition known to produce or be associated with immunosuppression.
  • Have received cytotoxic therapy in the previous 5 years.
  • A medical condition that, in the opinion of the Principal Investigator (PI), could adversely impact the subject's participation, safety, or conduct of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01491607

Locations
United States, Florida
Miami Research Associates
Miami, Florida, United States, 33143
United States, New York
Rochester Clinical Research
Rochester, New York, United States, 14609
United States, South Carolina
Coastal Carolina Research Center
Mt. Pleasant, South Carolina, United States, 29464
United States, Utah
Jean Brown Research
Salt Lake City, Utah, United States, 84124
Sponsors and Collaborators
Emergent BioSolutions
Investigators
Principal Investigator: Robert Hopkins, MD, MPH, TM Emergent BioSolutions Inc.
  More Information

No publications provided

Responsible Party: Emergent BioSolutions
ClinicalTrials.gov Identifier: NCT01491607     History of Changes
Other Study ID Numbers: EBS.AVA.006, HHSO100200700037C
Study First Received: December 12, 2011
Results First Received: July 11, 2013
Last Updated: September 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Emergent BioSolutions:
post-exposure prophylaxis
toxin neutralization assay

ClinicalTrials.gov processed this record on October 29, 2014