Clinical Trial: Trial of Yellow Fever Inactivated Vaccine

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

Official Title: Randomized, Double Blind, Controlled Phase I Trial of the Safety, Tolerability,and Immunogenicity of Graded Doses of XRX-001 Yellow Fever 17D, Inactivated Vaccine, Alum Ad

Brief Summary:

The Phase 1 trial is a single-center, randomized, double blind, placebo-controlled, dose-ranging out-patient study designed to provide the first clinical data on the safety, tolerability and immunogenicity of XRX-001 inactivated yellow fever vaccine in 60 healthy male and female volunteers, 18-49 years of age. Subjects will receive two inoculations of one of two dose levels of XRX-001 vaccine. A control group will receive placebo.

Safety will be determined by the incidence and severity of adverse events in each treatment group and in the combined cohorts in the double blind treatment period up to 42 days post-vaccination. Subjects will also be followed-up at 3, 6 and 12 months to determine severe adverse events (SAEs) and changes in health status.

Efficacy will be assessed by neutralizing antibody response to the vaccine. The co-primary immunogenicity endpoints will be the dose-response analysis of seroconversion rates (fourfold or greater increase in neutralizing antibody titer between baseline and Day 42) and of the 50% plaque reduction neutralization test (PRNT50) geometric mean titers (GMT) at Day 42.

Secondary immunogenicity endpoints will include:

  1. The seroconversion rates and GMT neutralizing antibody titers for all dose groups combined on Days 21 and 42.
  2. The reverse cumulative distribution curve of antibody titers on Days 21 and 42 for each dose group and for all dose groups combined
  3. The duration of antibody titers displaying the seroconversion rate and GMT across all time-points to Month 12, by treatment group and for both dose groups combined.

Detailed Summary:
Sponsor: GE Healthcare

Current Primary Outcome:

  • The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. [ Time Frame: Measured from 0 up to 21 Days ]

    Subjects were observed for 60 minutes (greater than of equal to 60 minutes and less than of equal to 90 minutes) after vaccine adminstration for any signs or symptoms or local and/or systematic intolerance to the test articles and vital signs were to be checked within the same observation timeframe.

    After vaccination, subjects were to complete a memory aid to record daily temperature, symptoms, and concomitant medications from Day-0 to Day-42.

    Subjects were to return to the clinic on Days 3, 10, 21, 24, 31, and 42 with a second vaccination given on Day 21.

    At each visit, study personnel were to conduct a structured adverse event (AE) interview, and subject were to use their memory aid to assist with the recall of symptoms experiences and daily oral temperatures.

  • The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. [ Time Frame: Measured from 22 up to 42 Days. ]

    Subjects were observed for 60 minutes (greater than of equal to 60 minutes and less than of equal to 90 minutes) after vaccine adminstration for any signs or symptoms or local and/or systematic intolerance to the test articles and vital signs were to be checked within the same observation timeframe.

    After vaccination,

    Original Primary Outcome: Safety will be determined by the incidence and severity of adverse events in each treatment group and in the combined cohorts in the double blind treatment period up to 42 days post-vaccination. Subjects will also be evaluated at 6 and 12 Months. [ Time Frame: 42 days, 6 and 12 months ]

    Current Secondary Outcome:

    • Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 [ Time Frame: Days 21 and 42, 12 months ]
      Secondary immunogenicity endpoints will use 2 dose levels of XRX-001 inactivated yellow fever vaccine determined by 50% plaque reduction neutralization test (PRNT50). Dose groups were to be compared for neutralizing antibody seroconverison rate, distribution of antibody titers, and geometric mean antibody titers (GMTs) to yellow fever 17D virus. The seroconversion rates and GMT neutralizing antibody titers for each dose group and all dose groups combined; The reverse cumulative distribution curve of antibody titers;
    • Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus. [ Time Frame: GMT titers measured at days 21, 31 and 42 for different dose rates. ]
      Geometric mean antibody titers (GMT) neutralizing antibody titers for each dose groups.


    Original Secondary Outcome: Secondary immunogenicity endpoints will include: - The seroconversion rates and GMT neutralizing antibody titers for each dose group and all dose groups combined; - The reverse cumulative distribution curve of antibody titers; [ Time Frame: Days 21 and 42, 12 months ]

    Information By: GE Healthcare

    Dates:
    Date Received: October 8, 2009
    Date Started: January 2010
    Date Completion:
    Last Updated: April 1, 2016
    Last Verified: April 2016