CESA 5.10 Investigation to Compare the Efficacy and Safety of the Adacolumn® Apheresis Device in Patients With Active Ulcerative Colitis

Inclusion criteria

• 18-75 years old
• Active ulcerative colitis documented by clinical symptoms, endoscopic findings and histology (in patient history)
• Moderate to severe active ulcerative colitis at baseline evaluation, defined as follows:

• Clinical activity idex (CAI) score > 6; and
• Stool frequency score of 2 or 3
• Colonic involvement with ulcerative colitis beyond 15 cm of the anal verge
• Ulcerative colitis for at least 3 months
• Adequate peripheral venous access to allow for completion of the apheresis treatments, as demonstrated by the ability to successfully undergo a brief venous access procedure
• Receiving one or more of the following medical therapies:

• Sulfasalazine, mesalamine and other 5-aminosalicylic acid (5-ASA) agents for 4 weeks or more with a stable dose for the last 2 weeks
• A maximum of 20 mg per day of prednisone with a stable dose for the last 2 weeks, or
• 6-mercaptopurine or azathioprine for 12 weeks or more with a stable dose for the last 4 weeks; OR

Have not received the above medical therapies due to intolerance or demonstrated non-response for the time periods specified below:

• Sulfasalazine, mesalamine and other 5-ASA agents for 2 weeks
• Prednisone for 2 weeks, or
• 6-mercaptopurine or azathioprine for 4 weeks
• For female subjects of child-bearing potential, a negative pregnancy test and agreement to use an effective contraceptive method or abstain from sexual intercourse during the course of the clinical investigation
• Agree to participate in the required follow-up visits
• Able to complete the diary
• Signed written informed consent document

Exclusion criteria

• Febrile (> 38ºC)
• Evidence of toxic megacolon
• Anticipated need for surgery within 12 weeks
• Known obstructive diseases of the gastrointestinal system
• Proctocolectomy, total colectomy, ileostomy, stoma or ileal pouch-anal anastomosis
• A history of allergic reaction to heparin or heparin-induced thrombocytopenia
• A history of hypersensitivity reaction associated with an apheresis procedure or intolerance of apheresis procedures
• Requires a central venous access catheter for the apheresis treatments
• Known infection with enteric pathogens, pathogenic ova or parasites, or a positive assay for C. difficile toxin
• Hypotension (systolic blood pressure < 90 mmHg and/or diastolic blood pressure < 65 mmHg) at screening visit only
• Uncontrolled hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 120 mmHg) despite medical therapy at screening visit only
• A history of myocardial infarction or unstable angina within the past 6 months
• A history of coronary artery bypass grafting surgery or angioplasty within the past 6 months
• A history of physical findings compatible with a cerebrovascular accident
• Congestive heart failure (New York Heart Association Class III or IV)
• Prosthetic heart valve, pacemaker or other permanent implant
• Severe cardiovascular or peripheral vascular disease
• Liver disease defined as levels of SGOT [AST], SGPT [ALT] or alkaline phosphatase > 2.5x the upper limit of the normal range for the laboratory performing test
• History of cirrhosis
• Renal insufficiency, defined as serum creatinine > 150% of the upper limit of the normal range for the laboratory performing the test
• Insulin-dependent type I or type II diabetes. (Patients receiving oral antidiabetic treatment can be included.)
• Known bleeding disorder (PT or PTT > 1.5x the upper limit of the normal range for the laboratory performing the test), or concomitant anticoagulant therapy for purposes other than apheresis treatment
• Prior history suggestive of a hypercoagulable disorder, including 1 or more episodes of pulmonary embolism or deep vein thrombosis
• Known infection with hepatitis B or C, or HIV
• Abnormal hematology parameters defined as severe anemia with hemoglobin < 8.5 g/dL, white blood cell count of < 3,500/ul and a granulocyte count < 2,000/μl
• Fibrinogen level > 700 mg/dL
• Major surgery within the past 6 weeks
• Infection:

• Active infections less than 4 weeks from successful completion of antibiotic treatment for routine bacterial infection
• Febrile viral infection within 4 weeks of entry into the clinical investigation
• Less than 12 weeks from conclusion of therapy for systemic fungal infections
• Malignancy within the past 2 years other than surgically cured skin carcinoma or cervical dysplasia (CIN I-II)
• History of dysplasia or carcinoma of the colon
• Current drug or alcohol abuse
• Pregnant, lactating or planning to become pregnant during the course of the clinical investigation
• Used within the last 30 days, an investigational drug, biologic or device or 5 half lives, if known, for any investigational drug or biologic
• Received cyclosporine or tacrolimus within the last 4 weeks
• Received infliximab within the last 8 weeks
• Received oral budesonide within the last 2 weeks
• Used topical therapy for ulcerative colitis within the last 2 weeks
• Previously received Adacolumn® treatments