Clinical Trial: A Phase I Study of the Safety, Reactogenicity, and Immunogenicity of Sm-TSP-2/Alhydrogel® With or Without GLA-AF for Intestinal Schistosomiasis in Healthy Adults

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I Study of the Safety, Reactogenicity, and Immunogenicity of Sm-TSP-2/Alhydrogel® With or Without GLA-AF for Intestinal Schistosomiasis in Healthy Adults

Brief Summary: This is a Phase I, first-in-human study of a vaccine against S. mansoni infection.The study will recruit 72 healthy adult males and non-pregnant females from a single clinical center to test two formulations of Sm-TSP-2 vaccine (using the Alhydrogel® only, and using Alhydrogel® plus GLA-AF), each at 3 different doses: 10ug, 30ug, and 100ug. The primary objective is to assess the safety and reactogenicity of ascending doses of Sm-TSP-2/Alhydrogel® (10ug, 30ug, or 100ug) with or without GLA-AF vaccine given as three doses administered on Days 1, 57, and 113.

Detailed Summary: This is a Phase I, first-in-human study of a vaccine against S. mansoni infection.The study will recruit 72 healthy adult males and non-pregnant females from a single clinical center to test two formulations of Sm-TSP-2 vaccine (using the Alhydrogel® only, and using Alhydrogel® plus GLA-AF), each at 3 different doses: 10ug, 30ug, and 100ug. The study will use a dose-escalation cohort design, in which escalation to the next dose cohort will be determined based on evaluation of pre-defined escalation criteria requiring 7 day safety data to be examined after all subjects in the current cohort have received their first dose of vaccine. For each Cohort (1-3), an initial 5 subjects (2 Sm-TSP-2/Alhydrogel®, 2 Sm-TSP-2/Alhydrogel®/GLA-AF, and 1 placebo) will be enrolled, randomized, vaccinated, and have completed Visit 2 (Day 3), before enrolling the rest of the cohort. As with dose-escalation decisions, evidence of significant reactogenicity will require further review prior to proceeding.Recruitment and enrollment into the study will occur on an ongoing basis, with each cohort being recruited and vaccinated in sequence. All subjects will be assigned investigational vaccine or placebo by randomization, and a double-blind design will be used (i.e., neither the subject nor the investigator will be aware of the study product assigned: Sm-TSP-2/Alhydrogel®, Sm-TSP-2/Alhydrogel®/GLA-AF, or placebo). Each subject will receive 3 vaccinations at Days 1, 57, and 113, and will be followed for a total of 12 months after the third dose. The study duration will be approximately 24 months, and subject participation duration will be approximately 16 months. The primary objective is to assess the safety and reactogenicity of ascending doses of Sm-TSP-2/Alhydrogel® (10ug, 30ug, or 100ug) with or without GLA-AF vaccine given as three doses administered on Days 1, 57, and 113. The secondary objectives include: (1) to assess the IgG antibody response using a
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • The occurrence of new-onset chronic medical conditions (including AESI) through 12 months after the third study vaccination. [ Time Frame: Through 12 months after the third study vaccination ( Day 478) ]
  • The occurrence of solicited injection site reactogenicity on the day of each study vaccination through 7 days after each study vaccination [ Time Frame: Day 113-120 ]
  • The occurrence of solicited injection site reactogenicity on the day of each study vaccination through 7 days after each study vaccination [ Time Frame: Day 57-64 ]
  • The occurrence of solicited injection site reactogenicity on the day of each study vaccination through 7 days after each study vaccination. [ Time Frame: Day 1-8 ]
  • The occurrence of solicited systemic reactogenicity on the day of each study vaccination through 7 days after each study vaccination. [ Time Frame: Day 113-120 ]
  • The occurrence of solicited systemic reactogenicity on the day of each study vaccination through 7 days after each study vaccination [ Time Frame: Day 1-8 ]
  • The occurrence of solicited systemic reactogenicity on the day of each study vaccination through 7 days after each study vaccination. [ Time Frame: Day 57-64 ]
  • The occurrence of study vaccine-related SAEs from the time of the first study vaccination through approximately 12 months after the last study vaccination [ Time Frame: Day 1-12 months after the last study vaccination ]
  • The occurrence of vaccine-related clinical safety laboratory adverse events [ Time Fr

    Original Primary Outcome:

    • The occurrence of new-onset chronic medical conditions (including AESI) through 12 months after the third study vaccination. [ Time Frame: Through 12 months after the third study vaccination ( Day 478) ]
    • The occurrence of vaccine-related clinical safety laboratory adverse events [ Time Frame: Day 1 through Day 478 ]
    • The occurrence of study vaccine-related SAEs from the time of the first study vaccination through approximately 12 months after the last study vaccination [ Time Frame: Day 1 - Day 478 ]
    • The occurrence of solicited injection site reactogenicity on the day of each study vaccination through 7 days after each study vaccination. [ Time Frame: Day 1-8, Day 57-64, Day113-120 ]
    • The occurrence of solicited systemic reactogenicity on the day of each study vaccination through 7 days after each study vaccination. [ Time Frame: Day 1-8, Day 57-64, Day 113-120 ]


    Current Secondary Outcome:

    • The IgG antibody response using an indirect enzyme-linked immunosorbent assay (ELISA) on the day of each dose, 14 days after each dose, and 3 and 6 months after the third dose of Sm-TSP-2/Alhydrogel (10ug, 30ug, or 100ug) with or without GLA-AF [ Time Frame: Days 1, 5, 57, 71, 113,127, 203 and 293 ]
    • The IgG level using an indirect enzyme-linked immunosorbent assay (ELISA) at Day 127 [ Time Frame: Day 127 ]


    Original Secondary Outcome: The IgG level using an indirect enzyme-linked immunosorbent assay (ELISA) at Day 127 [ Time Frame: Day 127 ]

    Information By: National Institute of Allergy and Infectious Diseases (NIAID)

    Dates:
    Date Received: January 8, 2015
    Date Started: February 4, 2015
    Date Completion: February 21, 2017
    Last Updated: February 9, 2017
    Last Verified: December 7, 2016