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

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: A Phase 1 Randomized Double-Blind Positive-Controlled Ascending Dose Study to Evaluate the Safety and Immunogenicity of a Replication-Competent Adenovirus Serotype 4 Anthrax

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.

Detailed Summary: A Phase 1, randomized, double-blind, positive controlled, increasing dose clinical trial in healthy adult subjects at multiple sites. The study will assess safety and immunogenicity of two adenovirus vaccine candidates against anthrax compared to the positive control, Anthrax Vaccine Adsorbed (AVA). The trial will enroll 108 subjects in the anthrax vector vaccine arms and 12 subjects in the AVA positive control subjects. The study will look at three different dose of oral dosages of Ad4-PA (protective antigen) and Ad4-PA-GPI (10^9, 10^10, 10^11 vp/dose)as well as 3 vaccine administration schedules (1 and 15 days; 1 and 29 days; 1, 15, and 29 days); 2 of 3 schedules will include an intramuscular (IM) AVA booster immunization, 1 schedule will include 3 vaccine administrations of Ad4-PA or Ad4-PA-GPI (glycosylphosphatidylinositol) alone, and 1 schedule will include 3 vaccine administrations of AVA alone.
Sponsor: PaxVax, Inc.

Current Primary Outcome: The safety, tolerability and immunogenicity of the Ad4 PA and Ad4 PA GPI vaccines across a range of dosages and schedules. [ Time Frame: Day 1 through Day 211 ]

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).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Antibody response of the Ad4-PA formulation to Ad4 PA GPI [ Time Frame: Day 1 through Day 85 (Day 211 if Day 85 is positive) ]
    Antibody response will be tested via enzyme-linked immunosorbent assay (ELISA) and the peak PA-ELISA titer defined as the highest ELISA titer achieved by a subject at any time between the first post-vaccination visit and Day 85
  • Antibody response of the Ad4-PA and Ad4-PA-GPI vaccination regimens to the anticipated AVA PEP regimen. [ Time Frame: Days 1 through 85 (Day 211 if Day 85 is positive) ]
    Antibody response will be tested via ELISA and the peak PA-ELISA titer defined as the highest ELISA titer achieved by a subject at any time between the first post-vaccination visit and Day 85.
  • Antibody response induced by 3 different dosages of Ad4 PA and Ad4 PA GPI. [ Time Frame: Days 1 through 85 (Day 211 if Day 85 is positive) ]
    Antibody response will be tested via ELISA and the peak PA-ELISA titer defined as the highest ELISA titer achieved by a subject at any time between the first post-vaccination visit and Day 85 and titers will be compared across the 3 different dosages of Ad4 PA and Ad4 PA GPI (10^9, 10^10, 10^11).
  • TNA and antibody response induced by Ad4 PA and Ad4 PA GPI on 3 different vaccination schedules. [ Time Frame: Days 1 through 85 (Day 211 if Day 85 is positive) ]

    Antibody response will be tested via ELISA and the peak PA-ELISA titer defined as the highest ELISA titer achieved by a subject at any time between the first post-vaccination visit and Day 85, and compared among 3 vaccine schedules:

    1. Day 1: Ad4-PA or Ad4-PA-GPI, Day 15 placebo Day 29 AVA boost;
    2. Day 1:Ad4-PA or Ad4-PA-GPI, Day 15 AVA boost + Placebo; and
    3. Days 1, 15 and 29: Ad4-PA or Ad4-PA-GPI
  • Pre-existing Ad4 immunity on TNA and PA-ELISA response induced by Ad4 PA and Ad4 PA GPI. [ Time Frame: Days 1 through 85 (Day 211 if Day 85 is positive) ]
    Antibody response will be tested via ELISA and the impact of pre-existing Ad4 serostatus (positive/negative) on TNA and PA-ELISA will be evaluated
  • Evaluate the kinetics of the TNA and PA-ELISA antibody response induced by 3 different doses of Ad4 PA and Ad4 PA GPI on 3 different administration schedules. [ Time Frame: Days 1 through 85 (Day 211 if Day 85 is positive) ]
    TNA and PA-ELISA titer at each post-vaccination visit as measured by ELISA will be compared across each dose group (10^9, 10^10 and 10^11 vp) and dosing schedule. In addition, the time to peak pre-boost TNA titer and to peak pre-boost PA-ELISA titer will be compared across each dose group and dosing schedule. Cumulative TNA and PA-ELISA seroconversion through each post-vaccination visit and through Day 85
  • In vivo replication/excretion of the Ad4 PA and Ad4 PA GPI vaccines [ Time Frame: Days 1 through 211 ]
    The duration of in vivo replication/excretion will be measured by the Ad4 MN seroconversion and titer measured via ELISA testing. Vaccine take defined as either Ad4 micro-neutralizing (MN) seroconversion and/or detection of vaccine shedding measured by polymerase chain reaction (PCR) and confirmed by culture at any time point from Day 1 through Day 211


Original Secondary Outcome: Same as current

Information By: PaxVax, Inc.

Dates:
Date Received: October 16, 2013
Date Started: October 2013
Date Completion: February 2015
Last Updated: July 25, 2014
Last Verified: July 2014