Adacolumn in Refractory UC Patients Trial

Study Overview
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Brief Summary
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The objectives of the study are to observe and document the efficacy and safety of 5 or more Adacolumn treatments, administered once weekly over 5 or more weeks, in a specific subset of ulcerative colitis patients. The patient subset of interest is those with moderate/severe, steroid-dependent, active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biological agents.

Official Title
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Multicentre Investigation of the Efficacy and Safety of Adacolumn® GMA in Patients With Steroid-Dependent Active Ulcerative Colitis and Insufficient Response or Intolerance to Immunosuppressants and/or Biological Therapies

Conditions
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Ulcerative Colitis, Active Moderate

Intervention / Treatment
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* Device: (GMA) Adsorptive Apheresis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients enrolled into the study will be between 18 and 75 years old and have moderate to severe, steroid-dependent, active ulcerative colitis documented by clinical symptoms, endoscopic findings and histology. Patients will have an ulcerative colitis clinical activity (CAI) of ≥6 and an endoscopic activity index (EAI) of ≥4. Patients will have an insufficient response or intolerance to immunosuppressants and/or biological treatment agents. Patients are required to have adequate peripheral venous access to allow completion of apheresis treatment. Exclusion Criteria: - A patient will be excluded from the study if he/she meets any of the following criteria: Is febrile (body temperature >38ºC). Has evidence of toxic megacolon. Has known obstructive disease of the gastrointestinal system. Is anticipated to need surgery within the next 24 weeks. Has a history of hypersensitivity reaction associated with an apheresis procedure or an intolerance to apheresis procedures. Has proctocolectomy, total colectomy, ileostomy, stoma or ileal pouch-anal anastomosis. Has a history of allergic reaction to heparin or of heparin-induced thrombocytopenia. Has a known infection with enteric pathogens, pathogenic ova or parasites, or a positive test for cytomegalovirus. Has symptomatic hypotension. Has a history of physical findings consistent with a cerebrovascular accident. Has a history of myocardial infarction or unstable angina within the previous 6 months. Has undergone coronary artery bypass graft surgery or angioplasty within the previous 6 months. Has congestive heart failure (New York Heart Association Class III or IV). Has a prosthetic heart valve, pacemaker or other permanent implant. Has severe cardiovascular or peripheral vascular disease. Has liver disease defined as levels of aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) or alkaline phosphatase of greater than 2.5 × the upper limit of the normal range for the laboratory performing the test. Has a history of cirrhosis. Has a known bleeding disorder (prothrombin time [PT] or partial thromboplastin time [PTT] greater than 1.5 × the upper limit of the normal range for the laboratory performing the test) or requires concomitant anticoagulant therapy for purposes other than apheresis treatment. Has a prior history suggestive of a hypercoagulable disorder, including 1 or more episodes of pulmonary embolism or deep vein thrombosis. Has a known infection with hepatitis B or C or human immunodeficiency virus. Has abnormal haematology parameters defined as severe anaemia with haemoglobin <8.5 g/dL, white blood cell count <3500/µL or granulocyte count <2000/µL. Has a fibrinogen level >700 mg/dL. Has renal insufficiency, defined as a serum creatinine level greater than 150% of the upper limit of the normal range for the laboratory performing the test. Has had major surgery within the previous 6 weeks. Has any of the following types of infection: An active infection within 4 weeks of successful completion of antibiotic treatment for a bacterial infection. Febrile viral infection within the 4 weeks prior to entry into the study. Systemic fungal infection that required therapy which was completed within the 12 weeks prior to entry into the study. Current drug or alcohol abuse. Is pregnant, lactating or planning to become pregnant during the study. Has used an investigational medicinal product, biologic agent or device within the last 30 days. Adults lacking capacity who are unable to give consent by themselves due to physical and or mental incapacity. Prisoners and patients who have undergone psychiatric treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adacolumn<br> | Device: (GMA) Adsorptive Apheresis<br>* Patients will be treated with once-weekly Adacolumn® apheresis over 5 consecutive weeks; treatment can be extended to up to 10 treatments administered once weekly over 10 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy endpoint is the ulcerative colitis remission rate at Week 12, defined as a CAI (Rachmilewitz) score of ≤4. |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ulcerative colitis response rate at Week 12, with response defined as a reduction in CAI of ≥3. |  | 12 weeks | 
| Response and remission rates at Weeks 24 and 48 |  | 12 weeks | 
| Change from Baseline in CAI at Weeks 12, 24 and 48 |  | 12 weeks, 24 weeks and 48 weeks | 
| Change from Baseline in EAI at Week 12 |  | 12 weeks | 
| Time to remission and response |  | Baseline | 
| The proportion of patients reaching steroid-free remission/steroid-free response at any visit and by visit at Weeks 12, 24 and 48. |  | 12 weeks, 24 weeks and 48 weeks | 
| Time to steroid-free remission and response. |  | Baseline | 
| Colectomy rate at Week 96 |  | 96 weeks | 
| Change from Baseline in concomitant medication (steroid) dose at Weeks 12, 24 and 48. |  | 12 weeks, 24 weeks and 48 weeks | 
| Quality of life changes based on the Short Health Scale for ulcerative colitis at Weeks 5, 12, 24 and 48. |  | 5 weeks, 12 weeks, 24 weeks and 48 weeks |