Clinical trial NCT01263691: Safety, Tolerability and Immunogenicity Study of AV7909 Anthrax Vaccine in Healthy Adults
Official title: A Parallel-arm, Double-blind, Randomized, Placebo-controlled, Dose-ranging Clinical Trial Evaluating the Safety, Tolerability and Immunogenicity of AV7909 in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bacillus Anthracis (Anthrax) Infection
Keywords: AVA
AV7909
Anthrax vaccine
Lead sponsor: Emergent BioSolutions
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Department of Health and Human Services
First posted: 2010-12-21
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this Phase 1 clinical trial is to evaluate the safety, tolerability, and immunogenicity of AV7909 anthrax vaccine in healthy adults. In this study, healthy male and female subjects between 18 and 50 years of age will receive vaccinations via the intramuscular (IM) route at Days 0 and 14. Safety and tolerability will be evaluated via laboratory tests, physical examinations, vital signs, adverse events (AEs), concomitant medications, and local and systemic signs and symptoms of reactogenicity.

Detailed description: AV7909 is a new vaccine which is a combination of BioThrax (also called anthrax vaccine, adsorbed or AVA), a FDA-licensed vaccine, and CPG 7909. CPG 7909 is a synthetic short DNA sequence that has been shown to be an effective vaccine adjuvant, and one which increases the speed and the degree of the immune response to Protective Antigen (PA), the major vaccine antigen. In the current study, the safety, tolerability, and antibody response to PA will be studied for four different combinations of AVA and CPG 7909, and compared to both AVA and a saline placebo. All formulations of AV7909 have the same or less AVA than the licensed AVA vaccine and all have less CPG 7909 per dose than the formulation used in the first Phase I volunteer study of CPG 7909 combined with AVA.

Eligibility criteria: Inclusion Criteria:

* Be between 18 and 50 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.
* Have negative values for the following tests at Screening: Hepatitis C antibody, anti-Human Immunodeficiency Virus (Anti-HIV-1/-2/-O), and anti-Hepatitis B Core Antigen (Anti-HBc).
* Be willing and capable of complying with all aspects of the protocol through completion of the required visits.
* Have not donated blood in the preceding 8 weeks and are willing to not donate blood or plasma within 56 days after dosing.
* Have adequate venous access for repeat phlebotomies.
* Have read, understood and signed an informed consent form.

Exclusion Criteria:

Key Exclusion Criteria:

* A known anaphylactic response, severe systematic response, or serious hypersensitivity reaction to a prior immunization.
* Prior immunization with anthrax vaccine, recombinant Protective Antigen (rPA) vaccine, or known exposure to anthrax organisms.
* Have previously served in the military or plans to enlist in the military from Screening through Day 84.
* Have participated in anthrax therapeutic or vaccine trials (monoclonal anti-protective antigen (PA) or anthrax immune globulins or anthrax vaccines).
* Participation in any investigational clinical trial within 30 days preceding the Screening visit or planning to participate in a clinical trial requiring dosing through the Day 194 visit.
* A history of drug or alcohol abuse within 12 months prior to Screening, or a positive result on a urine drug screen for amphetamines, barbiturates, benzodiazepines, cocaine, marijuana, methylenedioxymethamphetamine opiates, oxycodone, phencyclidine, propoxyphene, or tricyclic antidepressants.
* Blood pressure greater than 145 millimeters of mercury (mmHg) systolic or 90 mmHg diastolic.
* Past history of significant autoimmune disease such as rheumatoid arthritis, lupus erythematous, psoriasis, glomerulonephritis, or autoimmune thyroiditis.
* 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.

Primary outcomes:
measure: Incidence of Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Vaccination (Day 0)
timeFrame: Days 0-6
measure: Percentage of Subjects With Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Vaccination (Day 0)
timeFrame: Days 0-6
measure: Incidence of Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Vaccination (Day 14)
timeFrame: Days 14-20
measure: Percentage of Subjects With Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Vaccination (Day 14)
timeFrame: Days 14-20
measure: Incidence of Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Injection (Day 0)
timeFrame: Days 0-6
measure: Percentage of Subjects With Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Injection (Day 0)
timeFrame: Days 0-6
measure: Incidence of Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Injection (Day 14)
timeFrame: Days 14-20
measure: Percentage of Subjects With Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Injection (Day 14)
timeFrame: Days 14-20
measure: Incidence of Hematology, Serum Chemistry, and Urinalysis Abnormalities Reported as Adverse Events
timeFrame: Days 0-56
measure: Percentage of Subjects With Hematology, Serum Chemistry, and Urinalysis Abnormalities Reported as Adverse Events
timeFrame: Days 0-56
Secondary outcomes:
measure: Peak TNA NF50 GMT for All Subjects in the Immunogenicity Population and by Gender After IM Administration of Investigational Product on Days 0 and 14.
timeFrame: Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.
measure: Median Time to Peak TNA NF50 GMT for All Subjects in the Immunogenicity Population and by Gender After IM Administration of Investigational Product on Days 0 and 14.
timeFrame: Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.
measure: TNA NF50 GMTs Across Study Days After IM Administration of Investigational Product on Days 0 and 14.
timeFrame: Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.
Other outcomes:
Locations:
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Salt Lake City
country: United States
facility: Jean Brown Research
state: Utah
Study officials:
affiliation: Emergent Biosolutions, Inc.
name: Edward Bernton, MD
role: STUDY_DIRECTOR
References:
citation: Hopkins RJ, Daczkowski NF, Kaptur PE, Muse D, Sheldon E, LaForce C, Sari S, Rudge TL, Bernton E. Randomized, double-blind, placebo-controlled, safety and immunogenicity study of 4 formulations of Anthrax Vaccine Adsorbed plus CPG 7909 (AV7909) in healthy adult volunteers. Vaccine. 2013 Jun 26;31(30):3051-8. doi: 10.1016/j.vaccine.2013.04.063. Epub 2013 May 10.