Schistosomiasis
Conditions
Keywords
AP 10-701, healthy adults, Immunogenicity, Phase Ib, Reactogenicity, Safety, Schistosomiasis, Sm-TSP-2/Alhydrogel®
Brief summary
The study will be conducted as a randomized, controlled, double blind Phase 1b dose-escalating clinical trial in up to 60 healthy adult males and non-pregnant females living in the S. mansoni-endemic area of Americaninhas, Brazil. The primary objective of this trial is to assess the safety and reactogenicity of ascending doses of Sm-TSP-2/Alhydrogel(R) (10mcg, 30mcg, or 100mcg) vaccine with or without AP 10-701 given as three doses administered on Days 1, 57, and 113.
Detailed description
The study will be conducted as a randomized, controlled, double blind Phase 1b dose-escalating clinical trial in up to 60 healthy adult males and non-pregnant females living in the S. mansoni-endemic area of Americaninhas, Brazil. The study will recruit up to 60 healthy adult males and non-pregnant females to test two formulations of Sm-TSP-2 vaccine (adjuvanted with Alhydrogel(R) only, or with Alhydrogel(R) plus AP 10-701), each at 3 different doses of antigen: 10mcg, 30mcg, and 100mcg. 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. Cohorts will be enrolled sequentially. For each Cohort (1-3), an initial 5 subjects (2 Sm-TSP-2/Alhydrogel(R), 2 Sm-TSP-2/Alhydrogel(R)/AP 10-701, and 1 Euvax B Hepatitis B vaccine) will be enrolled, randomized, vaccinated, and have completed Visit 02 (Day 2), before enrolling the rest of the cohort. As with dose-escalation decisions, evidence of significant reactogenicity will require further review prior to proceeding. The primary objective of this trial is to assess the safety and reactogenicity of ascending doses of Sm-TSP-2/Alhydrogel(R) (10mcg, 30mcg, or 100mcg) vaccine with or without AP 10-701 given as three doses administered on Days 1, 57, and 113. The secondary objectives used to evaluate the immunogenicity are: (1) to assess the IgG antibody response to Sm-TSP-2 using an indirect enzyme-linked immunosorbent assay (ELISA) at Day 127, (2) to assess the IgG antibody response to Sm-TSP-2 using an indirect ELISA at 14 days after dose one and two and Days 203, 293, and 478 (3, 6, and 12 months after the third dose) of Sm-TSP-2/Alhydrogel(R) (10mcg, 30mcg, or 100mcg) with or without AP 10-701, and (3) to assess the duration of the IgG antibody response to Sm-TSP-2 using an indirect ELISA following receipt of three doses of Sm-TSP-2/Alhydrogel(R) (10mcg, 30mcg, or 100mcg) with or without AP 10-701.
Interventions
BIOLOGICALGLA-AF
Previously referred to as Gluco-pyranosylphospho-lipid A aqueous formulation (GLA-AF). It is a toll-like receptor-4 agonist
BIOLOGICALHepatitis B Virus Vaccine (Recombinant)
A non-infectious subunit viral vaccine derived from hepatitis B surface antigen (HBsAg) produced in yeast cells.
BIOLOGICALSm-TSP-2/Alhydrogel
Sm-TSP-2/Alhydrogel
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
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 at the time of enrollment. 4. Are in good health, as determined by vital signs (oral temperature, pulse, and blood pressure), medical history, and brief physical examination at screening. -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, 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 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 corticosteroids as outlined in the Subjects
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The occurrence of solicited injection site reactogenicity | From Day 1 to Day 7 |
| The occurrence of study vaccine-related SAEs | From Day 1 to Day 478 |
| The occurrence of vaccine-related clinical safety laboratory adverse events | Day 113 |
| The occurrence of new-onset chronic medical conditions (including AESI) | From Day 1 to Day 478 |
| The occurrence of solicited systemic reactogenicity | From Day 1 to Day 7 |
Secondary
| Measure | Time frame |
|---|---|
| The anti-Sm-TSP-2 IgG level using an indirect ELISA | Day 127 |
| The anti-Sm-TSP-2 IgG antibody response using an indirect ELISA | Day 15 |
Countries
Brazil
Outcome results
None listed