Experimental Infection of Hookworm-naïve Adults With Dermally-applied Infectious Necator Americanus Hookworm Larvae

Open-label, dose-escalation clinical study in healthy, hookworm-naïve adults:

- Study site: George Washington Medical Faculty Associates, Washington, DC

- Number of participants: up to 30 in 3 cohorts of 10 volunteers each

In Cohort 1, ten (10) volunteers will receive an inoculum of 25 infectious Necator americanus
larvae. In Cohort 2, ten (10) volunteers will receive an inoculum of 50 infectious Necator
americanus larvae. In the optional Cohort 3, ten (10) volunteers will receive an inoculum of
75 infectious Necator americanus larvae.

The cohorts will be enrolled in a staggered fashion with safety data assessed prior to larval
dose escalation. Cohort 2 will be inoculated no earlier than 8 weeks after the last volunteer
is inoculated in Cohort 1. The optional Cohort 3 will be inoculated no sooner than 8 weeks
after the last volunteer is inoculated in Cohort 2. Cohort 3 will be enrolled only if the
tolerability of the experimental infection of Cohort 2 is acceptable and does not result in
significant adverse events.

Within each cohort, after Study Day 70, but before Study Day 77, up to 5 volunteers will
undergo capsule endoscopy in order to visualize and count adult N. americanus hookworms
residing in the intestine. Informed consent for capsule endoscopy will be obtained separately
from the primary study, and agreement or refusal will not impact on a subject's eligibility
to enroll or continue participation in the primary study.

Three months after larval administration, or at the time of study withdrawal, all
participants will receive a 3-dose treatment of albendazole (400 mg per dose) for clearance
of experimental infection.

- Larval inoculum schedule: Study Day 0 (single application)

- Route: applied to intact skin on the volar aspect of forearm

- Doses of N. americanus Larval Inoculum to be tested: 25, 50 and 75 infectious larvae
(high dose optional)

- Study duration: 6 months per study participant; total duration of the study estimated at
approximately 13 months

- Anthelmintic treatment: 3 months post larval inoculum, or at study withdrawal, 3-dose
treatment with 400 mg albendazole

Inclusion Criteria:

- Males or females between 18 and 45 years, inclusive.

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

- Available for the duration of the trial (6 months).

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

Exclusion Criteria:

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

- Participant unwilling to use reliable contraception methods while participating in the
study (if female and not surgically sterile, abstinent or at least 2 years
post-menopausal).

- 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.

- 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).

- Laboratory evidence of hematologic disease (hemoglobin <11.5 g/dl [females] or <12.5
g/dl [males]; absolute leukocyte count <3.6 or >10.7 x 103/mm3; absolute neutrophil
count [ANC] <1.7 x 103/mm3; absolute lymphocyte count <0.7 x 103/mm3; or platelet
count <140 x 103/mm3).

- History of iron deficiency anemia.

- History of hypoalbuminemia.

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

- Serum glucose (random) 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.

- 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 Day 0 of the
study.

- Positive ELISA 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 Day 0 of this study or planned use during the
study.

- Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to
the volunteer's expected Day 0 of the study.

- Receipt of blood products within the past 6 months.

- Known allergy to amphotericin B or gentamicin.

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