Schistosomiasis
Conditions
Keywords
Intestinal, Pichia pastoris, S. mansoni, Schistosomiasis, Sm-TSP-2/Alhydrogel, Sm-TSP-2/Alhydrogel/GLA-AF, vaccine
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 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.
Interventions
OTHERPlacebo
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.
BIOLOGICALSm-TSP-2/Alhydrogel
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.
BIOLOGICALSm-TSP-2/Alhydrogel/GLA-AF
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.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects must meet all of the following inclusion criteria in order to be eligible for participation in this study. 1. Provide written informed consent prior to any study procedures. 2. Able to understand and comply with planned study procedures and be available for all study visits. 3. Male or non-pregnant female aged 18 to 50, inclusive. 4. Are in good health, as determined by vital signs (oral temperature, pulse, and blood pressure), medical history, and targeted physical examination based on medical history.1 Existing medical diagnoses or conditions (except those in the Subject
Exclusion criteria
) must be deemed as stable chronic medical conditions. A stable chronic medical condition is defined as no change in prescription medication, dose, or frequency of medication in the last 3 months (90 days) and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months (180 days). Any change due to change of health care provider, insurance company, or that is done for financial reasons, as long as in the same class of medication, will not be considered a violation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a violation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity. Topical, nasal, and inhaled medications (with the exception of steroids as outlined in the Subjects
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The occurrence of vaccine-related clinical safety laboratory adverse events | Day 1-478 |
| The occurrence of solicited systemic reactogenicity on the day of each study vaccination through 7 days after each study vaccination | Day 1-8 |
| The occurrence of study vaccine-related SAEs from the time of the first study vaccination through approximately 12 months after the last study vaccination | Day 1-12 months after the last study vaccination |
| The occurrence of solicited systemic reactogenicity on the day of each study vaccination through 7 days after each study vaccination. | Day 113-120 |
| The occurrence of new-onset chronic medical conditions (including AESI) through 12 months after the third study vaccination. | 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 | Day 113-120 |
| The occurrence of solicited injection site reactogenicity on the day of each study vaccination through 7 days after each study vaccination. | Day 1-8 |
Secondary
| Measure | Time frame |
|---|---|
| The IgG level using an indirect enzyme-linked immunosorbent assay (ELISA) at Day 127 | Day 127 |
| 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 | Days 1, 5, 57, 71, 113,127, 203 and 293 |
Countries
United States
Outcome results
None listed