Clinical Trial: Safety and Immunogenicity of the Na-APR-1 Hookworm Vaccine in Healthy Adults

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

Official Title: Phase 1 Study of the Safety and Immunogenicity of Na-APR-1 (M74)/Alhydrogel® in Healthy Adults

Brief Summary: Hookworms digest hemoglobin from erythrocytes for use as an energy source via a proteolytic cascade that begins with the aspartic protease, APR-1. Vaccination with recombinant APR-1 has protected animals from infection in challenge studies. This study will evaluate the safety and immunogenicity of two formulations of Na-APR-1 (M74) in healthy adult volunteers when co-administered with different concentrations of the immunostimulant GLA-AF.

Detailed Summary:

Open-label, dose-escalation phase 1 clinical trial in healthy, hookworm-naïve adults:

  • Study site: George Washington Medical Faculty Associates, Washington, DC
  • Number of participants: 40 in 2 cohorts of 20.

In Cohort 1 five (5) volunteers will receive 30 µg Na-APR-1 (M74) /Alhydrogel®, five (5) will receive 30 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF, and ten (10) will receive 30 µg Na-APR-1 (M74) /Alhydrogel® plus 5 µg GLA-AF. In Cohort 2 five (5) volunteers will receive 100 µg Na-APR-1 (M74)/Alhydrogel®, five (5) will receive 100 µg Na-APR-1 (M74) /Alhydrogel® plus 2.5 µg GLA-AF, and ten (10) will receive 100 µg Na-APR-1 (M74)/Alhydrogel® plus 5 µg GLA-AF.

The cohorts will be enrolled in a staggered fashion with safety data assessed prior to the Na-APR-1 dose escalation from 30 to 100 µg. In addition, within each cohort, vaccinations will be staggered such that formulations containing 0, 2.5, and 5 µg GLA-AF will be tested sequentially: for example, those receiving Na-APR-1 (M74)/Alhydrogel® in combination with 2.5 µg GLA-AF will be vaccinated no sooner than 3 days after the last volunteer is vaccinated with the formulation containing no GLA-AF, whereas those vaccinated with Na-APR-1 (M74)/Alhydrogel® plus 5 µg GLA-AF will be vaccinated no sooner than 7 days after the last one receives the 2.5 µg GLA-AF formulation.

  • Immunization schedule: Study days 0, 56 and 112.
  • Route: IM in the deltoid muscle.
  • Doses of Na-APR-1 (M74) to be
    Sponsor: Baylor College of Medicine

    Current Primary Outcome: Vaccine-related Adverse Events [ Time Frame: Day 290 ]

    The frequency of immediate, systemic, and local injection site adverse events will be summarized. Adverse events will be assessed by study team members at 1 hour post-vaccination as well as 3, 7, 14, and 28 days following each vaccination. In addition, study participants will be asked to complete symptom diaries for the 7 days after each vaccination.


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • IgG antibody response to Na-APR-1 [ Time Frame: 14 days after final vaccination ]
      Dose and formulation of Na-APR-1 that generates the highest IgG antibody response at Day 126 (14 days after final vaccination), as determined by an indirect enzyme-linked immunosorbent assay (ELISA).
    • B cell response to Na-APR-1 [ Time Frame: Study Days 14, 70, 126, 140 and 290 ]
      Dose and formulation of the Na-APR-1 (M74) vaccine that results in the highest production of Na-APR-1 (M74) specific B cells and subtypes (memory or plasma).
    • Exploratory cellular immune response to Na-APR-1 [ Time Frame: Study Days 14, 70, 126, 140 and 290 ]
      Exploratory studies of the cellular immune responses to the Na APR-1 (M74) antigen both before and after immunization.


    Original Secondary Outcome: Same as current

    Information By: Baylor College of Medicine

    Dates:
    Date Received: October 25, 2012
    Date Started: September 2013
    Date Completion:
    Last Updated: May 30, 2017
    Last Verified: May 2017