Clinical Trial: Safety, Tolerability and Immunogenicity Study of AV7909 Anthrax Vaccine in Healthy Adults

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary: 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.
Sponsor: Emergent BioSolutions

Current Primary Outcome:

  • Incidence of Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Vaccination (Day 0) [ Time Frame: Days 0-6 ]

    Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the first injection (Day 0).

    All local reactions collected by subjects on diary cards were recorded as adverse events.

    Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."

    Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows:

    • Grade 0: none
    • Grade 1: <3 cm
    • Grade 2: 3 to 10 cm
    • Grade 3: >10 cm

    For all other ISRs, the following scale was used:

    • Grade 0: not present
    • Grade 1: present with no limitation of activity
    • Grade 2: interfering with daily activities or requiring non-narcotic treatment
    • Grade 3: preventing normal daily activities or requiring narcotic analgesia
  • Percentage of Subjects With Injection Site Rea

    Original Primary Outcome: Safety, as evaluated by adverse events and clinical laboratory tests [ Time Frame: Visits at Days 0, 1, 2, 7, 14, 21, 35, 42, 70, and 84 ]

    Sequential assessments of symptoms, physical exam findings, and clinical laboratory tests.


    Current Secondary Outcome:

    • 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. [ Time Frame: Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84. ]
      Toxin neutralizing antibody (TNA) 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). TNA NF50 is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. Values below the lower limit of quantitation (LLOQ) of the assay (ED50 of 33) were replaced with one-half the LLOQ (ED50 of 16.5) for calculation of geometric mean titer (GMT) and statistical analysis. GMT is based on log transformation.
    • 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. [ Time Frame: Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84. ]
      Toxin neutralizing antibody (TNA) 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). TNA NF50 is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. Values below the LLOQ of the assay (ED50 of 33) were replaced with one-half the LLOQ (ED50 of 16.5) for calculation of geometric mean titer (GMT) and statistical analysis. GMT is based on log transformation.
    • TNA NF50 GMTs Across Study Days After IM Administration of Investigational Product on Days 0 and 14. [ Time Frame: Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84. ]
      Toxin neutralizing antibody (TNA) 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). TNA NF50 is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. Values below the LLOQ of the assay (ED50 of 33) were replaced with one-half the LLOQ (ED50 of 16.5) for calculation of geometric mean titer (GMT) and statistical analysis. GMT is based on log transformation.


    Original Secondary Outcome: Immunogenicity four AV7909 formulations, compared with saline placebo and anthrax vaccine adsorbed (AVA) alone [ Time Frame: Visits through Day 84 after first immunization ]

    Anti-protective antigen (PA) antibody responses measured by anti-PA IgG and by the toxin neutralization assay (TNA).


    Information By: Emergent BioSolutions

    Dates:
    Date Received: December 17, 2010
    Date Started: December 2010
    Date Completion:
    Last Updated: August 1, 2014
    Last Verified: August 2014