Safety, Tolerance, Pharmacokinetics and Activity of HE3286 in Patients With Rheumatoid Arthritis

This is a Phase I/II, open label, dose ranging study of the safety, tolerance, and
anti-inflammatory activity of HE3286 in patients with rheumatoid arthritis. Patients will
receive study treatment (one of three open label doses) in addition to their current stable
dose of methotrexate. Safety (via monitoring of vital signs, physical examination changes,
ECG results, laboratory results, and adverse events), pharmacokinetics profiles (of HE3286
and methotrexate) and anti-inflammatory activity will be assessed over a treatment period of
29 days.

Main Inclusion Criteria:

- Male or female patient 18-75 years of age

- Patient with stable or active disease on a stable dose of methotrexate for at least 30
days prior to Day 1

- Patient has normal thyroid stimulating hormone (TSH) levels with or without thyroid
replacement therapy

- Patient is willing to abstain from consuming grapefruit containing products from 24
hours prior to dosing until the end of the study as it may affect the pharmacokinetic
measurements

- Patient has not experienced renal or liver disease by history and/or based on
laboratory results

- Patient has not experienced acute cardiac disease within 6 months prior to Screening

- Patient must provide voluntary, written, informed consent prior to screening
evaluations and be able to follow verbal and written instructions.

Main Exclusion Criteria:

- Functional status class IV according to The American College of Rheumatology (ACR)
criteria

- Patient who has a history of clinically significant cardiovascular disease (including
coronary artery disease), clinically significant hepatic, respiratory or renal
abnormalities, or clinically significant endocrine disorders (including diabetes)

- Patient with active Tuberculosis (TB) or evidence of latent TB without previous
adequate therapy

- Systemic autoimmune disorder (including, but not limited to, systemic lupus
erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed
connective tissue disease or any overlap syndrome)

- Inflammatory joint disease other than RA

- Patient who has received any of the following immunosuppressive drugs:

- Etanercept within 1 month of Day 1;

- Abatacept, adalimumab, infliximab, leflunomide, imuran, cyclosporin, anakinra,
sulfasalazine, bextra, celebrex or gold within 2 months of Day 1 or for
biological agents 6 half lives, whichever is greater;

- Rituximab within 1 year of Day 1

- Patient that is bed or wheelchair bound

- Patients taking prednisone within 2 weeks prior to Screening

- Patient requiring or receiving any of the following within thirty (30) days prior to
the screening visit: interleukins, steroids (i.e., anabolic steroids,
glucocorticoids), hormone replacement therapy (except stable low-dose HRT for at least
6-months prior to screening), birth control pills, anti-cancer chemotherapeutic agents
(except methotrexate), metabolic inhibitors (except methotrexate), concomitant
medications that prolong the QT/QTc interval

- Patient who has any clinically significant abnormalities in laboratory results at
Screening