The Immunological and Blood Effects of STA-5326 Mesylate on Patients With Crohn's Disease

• INCLUSION CRITERIA:

A subject is eligible for the study if all of the following criteria are met:

Has given written informed consent prior to Screening.

Is male or female aged 18 through 75 years.

Has CD diagnosed definitively prior to Screening (based upon clinical, endoscopic, radiologic imaging, or histological assessments).

Has a CDAI score of 220 to 450, inclusive.

If taking sulfasalazine or mesalamine, must have been using continuously for at least 2 months prior to randomization and at stable doses for at least 2 weeks prior to randomization.

If taking azathioprine, 6-mercaptopurine, or methotrexate, must have used continuously for at least 3 months prior to randomization and at stable doses for at least 1 month prior to randomization.

If taking oral antibiotics chronically, must have used continuously for at least 1 month prior to randomization and at stable doses for at least two weeks prior to randomization.

If taking corticosteroids, must be taking prednisone less than or equal to 20 mg daily (or equivalent), or budesonide less than or equal to 9 mg daily for at least 2 months prior to randomization and at stable doses for at least 2 weeks prior to randomization.

Not taking any potential CYP3A4 inhibitors/inducers (eg, macrolide antibiotics, HIV protease inhibitors, antifungals, grapefruit juice, St. John's Wort).

EXCLUSION CRITERIA:

A subject is excluded from the study if any of the following criteria are met:

General criteria:

Has any clinically significant disease (eg, renal, hepatic, neurological, cardiovascular, pulmonary, endocrinologic, psychiatric, hematologic, urologic, or other acute or chronic illness) that in the opinion of the investigator would make the subject an unsuitable candidate for this trial.

Is a woman who has a positive pregnancy test or who is breast-feeding

Is a woman of childbearing potential or a man who does not agree to use 2 forms of contraception during the course of the study and Follow-up period.

Has hypersensitivity to any of the components of STA 5326 mesylate drug product.

Has any of the following clinical chemistry values:

• AST greater than 2.0 x ULN.
• ALT greater than 2.0 x ULN.
• Serum bilirubin greater than 1.5 x ULN.
• Serum creatinine greater than 1.5 x ULN.
• Alkaline phosphatase greater than 2.5 x ULN.

Has a hemoglobin level less than 9 g/dL or hematocrit less than 30%.

Has a PT INR greater than 1.3 or PTT of 3 or more seconds longer than control values.

Has the following cell counts (cells/microliter):

• Platelets less than 100,000 or greater than 800,000.
• White blood count less than 3,500.
• Neutrophils less than 2000.

Has a history of any infection requiring intravenous antibiotics, a serious local infection (eg, cellulitis, abscess) or systemic infection (eg, pneumonia, septicemia) that occurred within 3 months of randomization.

Has a history of cancer within the past 5 years, with the exception of excised basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ.

Had a dependency for any illicit drug, chemical, or alcohol within the past 5 years.

Has a history of active tuberculosis, a positive PPD skin test, acute or chronic hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).

Gastrointestinal criteria:

Has a current ileostomy or colostomy.

Has a proctocolectomy or total colectomy.

Has short bowel syndrome requiring enteral or parenteral nutrition supplementation or total parenteral nutrition.

Has a stool sample positive for gastrointestinal infection (eg, Clostridium difficile toxin, etc.) during Screening.

Has a history or diagnosis of ulcerative or indeterminate colitis.

Had bowel surgery in the previous 3 months.

Had severe intestinal tract stenosis or fixed strictures causing symptomatic obstruction within 6 months prior to randomization.

Prior medication criteria relative to randomization:

Received parenteral corticosteroids or corticotropin within 1 month prior to randomization.

Has had regular use of aspirin or other non-steroidal anti-inflammatory drugs within 2 weeks prior to randomization (other than use of chronic low dose aspirin [81 mg per day] for cardioprotective effects).

Received any investigational drug within 3 months prior to randomization.

Received cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 2 months prior to randomization.

Received any biological product (eg, infliximab, adalimumab, natalizumab, etc.) within 3 months prior to randomization.

Ever received treatment with STA-5326 mesylate, IL-12 antibodies, or other specific IL-12 inhibitors.