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

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.

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 Exclusion Criteria), vitamins, and
contraceptives are permitted. 5. Vital signs (oral temperature, pulse, and blood pressure)
are all within normal protocol-defined ranges. Note: The normal protocol-defined ranges
for vital signs include (a) oral temperature less than 100.0°F, (b) pulse 50 to 100 bpm,
inclusive, (c) systolic blood pressure 85 to 150 mmHg, inclusive, and (d) diastolic blood
pressure 55 to 90 mmHg, inclusive. 6. Laboratory tests (alanine aminotransferase,
creatinine, white blood cells, hemoglobin, and platelets) are all within normal
protocol-defined reference ranges.33 The normal protocol-defined ranges for laboratory
tests include (a) alanine aminotransferase (ALT) of 32 IU/L or less for females or 44 IU/L
or less for males, (b) creatinine 1.0 mg/dL or less for females or 1.27 mg/dL or less for
males, (c) white blood cells (WBC) between 3.4 x10^3/uL and 10.8 x10^3/uL, inclusive, (d)
hemoglobin 11.1 g/dL or greater for females or 12.6 g/dL or greater for males, (e)
platelets between 150 x10^3/uL and 379 x10^3/uL, inclusive. Laboratory test results for
2nd and 3rd vaccinations may be at Grade 1 if considered unrelated to study product. 7.
Urinalysis with no greater than trace protein and negative for glucose. 8. Female subjects
of childbearing potential4 must agree to practice highly effective contraception5 for a
minimum of 30 days prior to study product exposure and through 30 days after last
vaccination.4 Female subjects who are surgically sterile via tubal sterilization,
bilateral oophorectomy or hysterectomy or who have been postmenopausal for greater than 1
year are not considered to be of childbearing potential.5 Note: Highly effective methods
of contraception are defined as having low failure rates (i.e. less than 1% per year) when
used consistently and correctly and may include, but are not limited to, abstinence from
intercourse with a male partner, monogamous relationship with a vasectomized partner, mal
e condoms or diaphragm with spermicide, intrauterine devices, and licensed hormonal
methods. 9. Female subjects of childbearing potential must have a negative urine pregnancy
test within 24 hours prior to study vaccination.

Exclusion Criteria:

All subjects who meet any of the following exclusion criteria at baseline will be excluded
from participation in the study. 1. Has had known infection due to S. mansoni or has
traveled to an endemic area for S. mansoni infection and, during that travel, was
potentially exposed to S. mansoni. 2. Has a positive urine pregnancy test prior to
vaccination (if female of childbearing potential), or has the intention to become pregnant
within 5 months after enrollment in this study. 3. Female subjects who are breastfeeding
or plan to breastfeed at any given time from the first study vaccination until 30 days
after their last study vaccination. 4. Has an acute illness, including an oral temperature
of 100.0 degree F or greater, within 72 hours prior to vaccination. 5. Evidence of
clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune,
diabetes, or renal disease by history, physical examination, and/or laboratory studies.
6.6 Includes the conditions and diagnoses defined as AESI in Section 9.3.3. 6. Is
immunosuppressed as a result of an underlying illness or treatment.7.7 Causes for
immunosuppression may include, but are not limited to, poorly-controlled diabetes
mellitus, cirrhosis, renal insufficiency, active neoplastic disease or a history of any
hematologic malignancy, connective tissue disease, organ transplant. 7. Using or intends
to continue using oral or parenteral steroids, high-dose inhaled steroids(> 800 microg/day
of beclomethasone dipropionate or equivalent) or other immunosuppressive or cytotoxic
drugs. 8. Positive hepatitis B surface antigen (HBsAg) 9. Positive confirmatory test for
HIV infection 10. Positive confirmatory test for hepatitis C virus (HCV) infection 11.
Volunteer has had a history of alcohol or illicit drug abuse during the past 24 months.
12. Received immunoglobulin or other blood products (with exception of Rho D
immunoglobulin) within 90 days prior to study vaccination. 13. History of a severe
allergic reaction or anaphylaxis to known components of the vaccine 14. Has an acute or
chronic medical condition that, in the opinion of the investigator, would render
participation in this study unsafe or would interfere with the evaluation of responses.
Note: This includes, but is not limited to: known liver disease, renal disease,
neurological disorders, visual field defects, cardiac disorders, pulmonary disorders,
diabetes mellitus, and transplant recipients. 15. History of splenectomy 16. Plans to
undergo surgery (elective or otherwise) from the time of enrollment through 1 month post
dose 3 vaccination. 17. Is participating or plans to participate in another clinical trial
with an interventional agent9 during the duration of the study. Note: This may include
other licensed or unlicensed vaccines, drugs, biologics, devices, blood products, or
medications. 18.Received any licensed live vaccine within 30 days or any licensed
inactivated vaccine within 14 days prior to the first study vaccination. Note: During
influenza season, subjects will be offered seasonal influenza vaccine prior to enrollment
into the study. 19. Planned receipt of any vaccine from the first study vaccination
through 1 month after the last study vaccination. 20. Have any diagnosis, current or past,
of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with
subject compliance or safety evaluations. 21. Has any condition that would, in the opinion
of the site investigator, place the subject at an unacceptable risk of injury or render
the subject unable to meet the requirements of the protocol.