Reslizumab to Prevent Post-treatment Eosinophilia in Loiasis

Background:

Loa loa is a parasitic worm that infects people in West and Central Africa and is spread by
the bite of a deerfly. Adult worms (macrofilariae) live under the skin and cause symptoms
such as swellings, itching, and hives. Smaller worms (microfilariae) are found in the
bloodstream. Diethylcarbamazine (DEC), the recommended medication for Loa loa infection, can
produce very serious side effects, especially in people with high numbers of parasites in the
blood. Researchers are investigating new treatments for Loa loa that have fewer or less
serious side effects. Researchers believe that a certain kind of blood cells called
eosinophils, which increase in the blood after DEC treatment, may be one of the causes of the
side effects seen with DEC treatment. Reslizumab is a drug that lowers eosinophils in the
blood. Giving reslizumab before DEC treatment might prevent the eosinophils from increasing
and reduce some of the side effects from DEC.

Objectives:

- To determine whether reslizumab can prevent or reduce the side effects of treatment with
DEC for Loa loa infection.

Eligibility:

Screening: Individuals between 18 and 65 years of age who have lived in or traveled to a
Loa-endemic region for at least 1 month

Treatment study: Individuals with Loa loa infection and low numbers of parasites in the blood

Design:

This study will last 24 months and will involve several visits to the National Institutes of
Health Clinical Center. Participants will be screened with a blood test for Loa loa
parasites. Those who have a low number of Loa loa parasites in the blood will be asked to
return for a full medical evaluation and the start of the treatment phase. Those who do not
have Loa loa parasites in the blood, or those who have a high number of Loa loa parasites in
the blood, are not eligible for this study treatment but may be eligible for other parasitic
disease studies conducted by the National Institutes of Health.

Participants will have an initial visit with a full physical evaluation, and blood and urine
tests (including leukapheresis to provide sufficient numbers of blood cells for testing).
Within 1 month of the first visit, participants will have a single infusion of either
reslizumab or a placebo. The infusion visit is estimated to last approximately 5 hours. Three
to 7 days after the infusion, participants will begin a 21-day course of DEC (taken by mouth)
to treat the infection. Participants will stay overnight at the Clinical Center during the
first 3 days of treatment with DEC to be monitored for side effects, and will continue to
take the DEC at home after the inpatient treatment. A study coordinator will call
participants each day to ask about any symptoms or side effects. Participants will be seen
for an additional eight outpatient follow-up visits (at days 7, 14, and 28, and months 3, 6,
12, 18, and 24) for evaluation of signs and symptoms of infection.

- INCLUSION CRITERIA: (Screening)

A subject will be eligible for participation in the screening portion of this protocol if
all of the following criteria apply:

1. Between 18 and 65 years of age

2. Residence in or travel to a Loa-endemic region for greater than 1 month

EXCLUSION CRITERIA: (Screening)

A subject will not be eligible for participation in the screening portion of this study if
any of the following conditions apply:

1. Known to be pregnant

2. Known to be HIV-positive

INCLUSION CRITERIA: (Interventional Study)

A subject will be eligible for participation in the interventional portion of the study
only if all of the following criteria apply:

1. The subject has documented loiasis with 0-5000 microfilariae/mL blood.

2. The subject agrees to storage of samples for study

3. A female subject is eligible for this study if she is any of the following:

- Not pregnant or breast-feeding.

- Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal
ligation or are post-menopausal, as defined by no menses in greater than or equal
to 1 year)

- Of childbearing potential but agrees to practice effective contraception* or
abstinence for 3 months after administration of the investigational study drug
(reslizumab or placebo)

- NOTE: Acceptable methods of contraception may include one or more of the
following: 1) male partner who is sterile prior to the female subject s
entry into the study and is the sole sexual partner for the female subject;
2) implants of levonorgestrel; 3) injectable progestogen, an intrauterine
device with a documented failure rate of less than 1percent; 4) oral
contraceptives; and 5) double barrier methods including diaphragm or condom
with a spermicide.

EXCLUSION CRITERIA: (Interventional Study)

A subject will not be eligible to participate in the interventional portion of the study if
any of the following conditions are fulfilled at the time of enrollment:

1. The subject tests positive for HIV infection or has any other known immunodeficiency.

2. The subject has a concomitant active infection with Onchocerca volvulus.

3. The subject has used any other investigational agent within the past 30 days.

4. The subject has used immunosuppressive agents (as listed in section 8.1) within the
past 30 days.

5. The subject has a history of allergic reaction to any antibody therapy or to DEC.

6. The subject has chronic kidney or liver disease.

7. The subject has any condition that, in the Investigator s opinion, places the subject
at undue risk by participating in the study.