Poly-ICLC to Prevent Respiratory Viral Infections A Safety Study

Polyinosinic-Polycytidylic acid stabilized with polylysine and carboxymethylcellulose
(Poly-ICLC), a stabilized double stranded RNA (dsRNA) therapeutic viral mimic activating
innate and adaptive immunity, has been in extensive preclinical and investigational clinical
therapeutic use as an intramuscular and intravenous compound, most recently in oncology
applications. Only recently have the mechanisms of action been more fully elucidated,
including induction of interferons, cytokines, and chemokines. Recognizing this, the
infectious disease applications have been pursued in in vitro and animal models. Intranasal
Poly-ICLC provides protection against mortality in animal models for multiple highly
pathogenic viruses including influenza, severe acute respiratory distress syndrome (SARS),
smallpox and Ebola. As its effects are not dependant on knowing the causative virus, an
effective compound that could be protective against several unknown respiratory viruses has
significant clinical appeal. While there is clinical safety data for intramuscular (IM)
Poly-ICLC, no clinical studies of nasal application of Poly-ICLC have been done.

This study is a phase I safety and pharmacokinetic trial of nasally applied Poly-ICLC. Human
volunteers will be administered increasing doses of nasal Poly-ICLC, with serial evaluation
of safety, tolerability, as well as exploratory markers of immune activation.

- INCLUSION CRITERIA:

Healthy volunteers age greater than or equal to 18 years and less than or equal to 70
years.

For 2 months prior to study drug administration, and through the last day of follow-up (Day
28), subjects must agree to:

- Not take any topical nasal medications (prescription or over the counter).

- Not receive live attenuated influenza vaccine (Flumist) or any other live attenuated
intranasal vaccine (licensed or research).

- Not receive any other investigational medications or vaccines.

Females of child-bearing potential must agree to use one of the following methods of
contraception for 4 weeks prior to date of screening evaluation through 4 weeks after study
drug administration:

- Be surgically sterile.

- Use oral contraceptives or other form of hormonal birth control including hormonal
vaginal rings or transdermal patches.

- Use an intra-uterine device (IUD).

- Use (by ensuring her male partner(s) uses) barrier contraception (condom) with a
spermicide.

- Any other equivalent (as judged by the investigative team) methods of contraception.

EXCLUSION CRITERIA:

A medical history that includes any of the following:

Any chronic medical problem that requires daily topical nasal medications.

Prior nasal or sinus surgery (including trans-nasal approaches of other organs such as
pituitary).

Allergic rhinitis, chronic sinusitis, or any other nasal inflammatory disease that requires
daily intranasal or oral medication.

Any chronic pulmonary conditions including (but not limited to) asthma, chronic obstructive
pulmonary disease, and chronic bronchitis.

Subjects with known hypersensitivity to interferons.

Any other medical history that in the opinion of the investigator significantly increases
the risk associated with a Phase I drug (e.g. Patients with coronary heart disease,
congestive heart failure, HIV, neuropsychiatric disorders, seizure disorder, autoimmune
disease, hepatic decompensation, poorly controlled endocrine disorders (including poorly
controlled diabetes, and actively hyper- or hypo-thyroid), hematological disorders (e.g.
leukopenia, thrombocytopenia), ophthalmologic disorders (excluding errors or
refractiveness) or other disorders for which symptoms of the condition could be similar to
interferon-related toxicity or that might be exacerbated by interferon would be excluded.
Patients with mild stable conditions, such as controlled hypertension, controlled diabetes,
and osteoarthritis would be permitted to enroll.)

Any history of habitual intranasal cocaine or other intranasal recreational drug use at any
time, or experimental intranasal concaine or other intranasal recreational drug use within
the last 10 years. (e.g. a 50 year old who tried cocaine once at age 20 is acceptable for
enrollment).

Women who are breast-feeding.

Positive urine or serum pregnancy test.

Participation in any research protocol that requires more than 100cc of blood to be given
in any 6-week period of time.