Pilot Study of RNS60 in Allergen-induced Bronchoconstriction

RNS60 has demonstrated significant anti-inflammatory effects in several animal models. The
goal of this study is to perform a mechanistic study showing regional improvements in
inflammation and to better understand the physiology of such improvements. Positron emission
tomography (PET) functional imaging will be used to determine whether RNS60 can attenuate
allergen-induced eosinophilic inflammation in asthma. The study will use a blinded,
crossover design where six patients will be treated with RNS60 and placebo for 21 days of
each treatment. Baseline and post-treatment imaging will be analyzed to determine effect.

Inclusion Criteria:

- Males or females with mild asthma (as defined by the National Institutes of Health
2002 Guidelines for the Diagnosis and Management of Asthma (2)) with symptoms more
than 2 times a week but less than once per day with normal FEV1 (> 80% predicted).

- Clinical history of allergic symptoms to cat or dust mite allergen and demonstrated
skin reactivity.

- Subjects must have a lifetime total of less than 5 pack years with no smoking in the
previous 5 years.

- Willing and able to give informed consent and adhere to the study protocol
requirements.

- Expressed the desire to participate in the study in an interview with the principal
investigator (PI).

- Age between 18 and 50 years.

Exclusion Criteria:

- Women of childbearing potential who are documented to be pregnant (based on blood
beta-human chorionic gonadotropin [HCG] testing) or who are nursing.

- The presence of spontaneous asthmatic episode or clinical evidence of upper
respiratory tract infection within the previous 6 weeks.

- Participation in research study involving a drug or biologic during the 30 days prior
to the study.

- Intolerance to albuterol, atropine, or lidocaine.

- Antihistamines within 7 days of the screening visit.

- Known exposure to agents that are associated with pulmonary disease (i.e. asbestos,
silica).

- Presence of other known pulmonary disease, coronary disease, congestive heart
failure, ventricular arrhythmias, history of a cerebrovascular accident, renal
failure (or creatinine > 1.5, if known), history of anaphylaxis, cirrhosis, diabetes
mellitus or presence of a significant disease, which in the opinion of the PI would
pose a significant risk for the subject or confound the results of the study.

- Use of systemic steroids, increased use of inhaled steroids, use of beta blockers and
monoamine oxidase (MAO) inhibitors or a visit for an asthma exacerbation within 1
month of the screening visit.

- A history of asthma-related respiratory failure requiring intubation.

- A history of hospitalization for asthma.

- Subjects with a high possibility of poor compliance with the study as judged by the
PI.

- Unresponsive to bronchodilator agents.

- Quantitative skin prick test at or below a dilution level of standardized cat
allergen extract of 1:2048 (4.88 BAU/ml) for subjects being challenged with cat
allergen.

- Quantitative skin prick test at or below a dilution level of standardized mite
allergen extract of 1:2048 (4.88 AU/ml) for subjects being challenged with either
mite allergen.

- Subjects who, by participating in any research study, will have a cumulative
radiation dose exceeding 50 mSv in the previous year.

- Contraindication to Methacholine challenge testing (heart attack or stroke in last 3
months, uncontrolled hypertension, or known aortic aneurysm).

- Body Mass Index (BMI) > 32.

- Individuals with known allergy or hypersensitivity to FDG will be excluded.