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
Condition: Schistosomiasis
MeSH terms: Schistosomiasis; Schistosomiasis mansoni
Study type: Interventional
Phase: Phase 1

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 description: 
      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 an indirect
      enzyme-linked immunosorbent assay (ELISA) at Day 127; (2) to assess the IgG antibody response
      using an indirect enzyme-linked immunosorbent assay (ELISA) at 14 days after dose one and two
      and Day 203 and 293 (3 and 6 months after the third dose) of Sm-TSP-2/Alhydrogel® (10ug,
      30ug, or 100ug) with or without GLA-AF; (3) To assess the duration of the IgG antibody
      response using an indirect enzyme-linked immunosorbent assay (ELISA) following receipt of
      three doses of Sm-TSP-2/Alhydrogel® (10ug, 30ug, or 100ug) with or without GLA-AF.
    

Intervention name(s): Placebo; Sm-TSP-2/Alhydrogel; Sm-TSP-2/Alhydrogel/GLA-AF
Intervention type(s): Other; Biological; Biological
Intervention description(s): Placebo: normal saline for parenteral administration. Group C. Group F, and Group I: single dose intramuscular (IM) Placebo (normal saline (0.9% NaCl) on Day 1, 57 and 113.; Sm-TSP-2/Alhydrogel. Group A: single dose IM 10mcg Sm-TSP-2/Alhydrogel® on Day1, 57 and 113. Group D: single dose intramuscular (IM) 30mcg Sm-TSP-2/Alhydrogel® on Day 1, 57 and 113. Group G: single dose intramuscular (IM) 100mcg Sm-TSP-2/Alhydrogel® on Day 1, 57 and 113.; Sm-TSP-2/Alhydrogel/GLA-AF. Group B: single dose intramuscular (IM) 10mcg Sm-TSP-2/Alhydrogel®/GLA-AF on Day 1, 57 and 113. Group E: single dose intramuscular (IM) 30mcg Sm-TSP-2/Alhydrogel®/GLA-AF on Day 1, 57 and 113. Group H: single dose intramuscular (IM) 100mcg Sm-TSP-2/Alhydrogel®/GLA-AF on Day 1, 57 and 113.
Intervention MeSH terms: Aluminum Hydroxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Intestinal; Pichia pastoris; S. mansoni; Schistosomiasis; Sm-TSP-2/Alhydrogel; Sm-TSP-2/Alhydrogel/GLA-AF; vaccine