Safety and Immunogenicity Study of Na-GST-1 With or Without CpG

This is a Phase 1 randomized double-blind dose-escalation clinical trial in healthy
hookworm-naïve adults conducted at the George Washington Medical Faculty Associates,
Washington, DC, and the George Washington University School of Medicine and Health Sciences,
Department of Microbiology, Immunology and Tropical Medicine, Washington, DC. In total, 24
subjects will be progressively enrolled into 2 cohorts of 12 subjects each. In the first
cohort 8 subjects will receive 30µg Na-GST-1/Alhydrogel co-administered with 500µg CpG 10104
and 4 subjects will receive 100µg Na-GST-1/Alhydrogel® only, in a randomized, double-blinded
fashion. In the second cohort 8 subjects will receive 100µg Na-GST-1/Alhydrogel
co-administered with 500µg CpG 10104 and 4 volunteers will receive 100µg Na-GST-1/Alhydrogel
only, in a randomized, double-blinded fashion. Vaccinations will be administered
intramuscularly in the deltoid muscle according to a 0, 2, 4-month schedule. Each subject
will participate in the study for 68 weeks (16 months) and the total duration of the study
is estimated at approximately 19 months.

Inclusion Criteria:

- Males or females between 18 and 50 years, inclusive.

- Good general health as determined by means of the screening procedure.

- Available for the duration of the trial (68 weeks).

- Willingness to participate in the study as evidenced by signing the informed consent
document.

- Able to understand and comply with planned study procedures.

Exclusion Criteria:

- Pregnancy as determined by a positive urine human choriogonadotropin (hCG) test (if
female).

- Participant unwilling to use reliable contraception up until one month following the
third immunization (if female and not surgically sterile, abstinent, at least 2 years
post-menopausal, or determined otherwise by medical evaluation to be sterile).

- Currently lactating and breast-feeding (if female).

- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,
rheumatologic, autoimmune, diabetes, or renal disease by history, physical
examination, and/or laboratory studies. A history of essential hypertension that is
well controlled by medication will not be considered exclusionary.

- Has a diagnosis of schizophrenia, bipolar disease or other major psychiatric
condition that would make compliance with study visits/procedures difficult (e.g.,
subject with psychoses or history of suicide attempt or gesture in the 3 years before
study entry, ongoing risk for suicide).

- Known or suspected immunodeficiency.

- Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than
1.25-times the upper reference limit).

- Laboratory evidence of renal disease (serum creatinine greater than 1.25-times the
upper reference limit, or more than trace protein or blood on urine dipstick testing
with the exception of greater than 1+ blood detected in females during menses).

- Laboratory evidence of hematologic disease (hemoglobin <11.1 g/dl [females] or <12.5
g/dl [males]; absolute leukocyte count <3400/mm3 or >10.8 x 103/mm3; or platelet
count <140,000/mm3).

- Laboratory evidence of a coagulopathy (activated PTT or PT INR greater than 1.1-times
the upper reference limit).

- Serum glucose greater than 1.2-times the upper reference limit.

- Other condition that in the opinion of the investigator would jeopardize the safety
or rights of a volunteer participating in the trial or would render the subject
unable to comply with the protocol.

- Planned participation in another investigational vaccine or drug trial within 30 days
of starting this study or until Visit #17 (6 months after the third vaccination).

- Volunteer has had medical, occupational, or family problems as a result of alcohol or
illicit drug use during the past 12 months.

- History of a severe allergic reaction or anaphylaxis.

- Severe asthma as defined by the need for daily use of inhalers, or emergency clinic
visit or hospitalization within 6 months of the volunteer's expected first
vaccination in the study.

- Positive test for hepatitis B surface antigen (HBsAg).

- Positive confirmatory test for HIV infection.

- Positive confirmatory test for hepatitis C virus (HCV) infection.

- Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within
30 days of the volunteer's expected first vaccination in this study or planned use up
to one month following the last vaccination.

- Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to
the volunteer's expected first vaccination in the study.

- Previous receipt of the Na-GST-1/Alhydrogel® hookworm vaccine.

- History of a surgical splenectomy.

- Receipt of blood products within the past 6 months.

- Pre-existing autoimmune or antibody-mediated diseases including but not limited to:
systemic lupus erythematosis, rheumatoid arthritis, multiple sclerosis, Sjogren's
syndrome, autoimmune thrombocytopenia; or laboratory evidence of possible autoimmune
disease determined by a positive anti-dsDNA titer, positive rheumatoid factor,
proteinuria and/or a positive ANA.

- History of previous infection with hookworm or residence for more than 6 months in a
community where hookworm is endemic.