Open-Label Adalimumab for Ulcerative Colitis Patients

Study Overview
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Brief Summary
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This is an open-label study of 20 patients designed to demonstrate the safety, tolerability and preliminary evidence of benefit of adalimumab in the treatment of subjects with Ulcerative Colitis, both in patients who have never received anit-TNF agents and in those who have lost response or developed intolerance to previous infliximab therapy.

Official Title
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An Open-Label Study of the Human Anti-TNF Monoclonal Antibody Adalimumab in Ulcerative Colitis Patients

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Males and females 18 years of age and older Female subjects must utilize a highly effective method of birth control throughout the study and for 70 days after study completion, or female subjects must not be of childbearing potential, defined as postmenopausal at least two years, or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy). A diagnosis of UC for greater than 3 months. UC diagnosis confirmed by endoscopy with exclusion of infectious cause. Active ulcerative colitis with a Mayo Clinic Score (see Appendix C) of 6 to 12 points with moderately-to-severely active disease on sigmoidoscopy (endoscopic subscore of at least 2) despite concurrent treatment with corticosteroids, and/or azathioprine or 6 mercaptopurine and/or 5-aminosalicylate-containing medications. Patients who previously have not responded to or could not tolerate corticosteroids (within the past 18 months), or azathioprine or 6 mercaptopurine (both within the past 5 years), or 5 aminosalicylate-containing medications (within the past 18 months) will not required to be taking concurrent therapy at enrollment. Either anti-TNF agent naïve or those with previous clinical response to infliximab therapy for UC with subsequent loss of response AND/OR are unable to tolerate further infliximab therapy for UC due to acute or delayed reactions, as defined by the investigator. Subjects must be able and willing to give written informed consent and to comply with the requirements of this study protocol. Adequate cardiac, renal and hepatic function as determined by principal investigator and demonstrated by screening laboratory evaluations, questionnaires, and physical examination results that are within normal limits. Exclusion Criteria History of cancer or lymphoproliferative disease other than a successfully and completely treated squamous cell or basal cell carcinoma of the skin. Subjects with a history of Listeria, Hepatitis B infection, central nervous system (CNS) demyelinating disease, or human immunodeficiency virus (HIV) or a history of previously untreated TB. See Appendix B. Subjects with Crohn?s Disease Subjects with symptomatic obstructive strictures Subjects who have had subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Kock pouch, or ileostomy for ulcerative colitis or are planning subtotal colectomy or colectomy within 8 weeks of starting the study medication. Subjects who are currently receiving total parenteral nutrition (TPN). Any investigational chemical agent in the past 30 days or 5 half-lives prior to screening (whichever is longer). Patients who have previously been treated with infliximab and responded, and then become intolerant to infliximab or lost response, can be treated >/= 4 weeks from their last infliximab dose. Antibiotic treatment for any systemic infection within 3 weeks prior to screening. Female subjects who are pregnant or breast-feeding. History of clinically significant drug or alcohol abuse in the prior year. Poorly controlled medical condition, including but not limited to diabetes with documented history of recurrent infections or cerebrovascular accidents (within 3 months). Subjects who have been on cyclosporine or tacrolimus within 4 weeks of screening. Subjects who have been on methotrexate within 4 weeks of screening.

Ages Eligible for Study
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Minimum Age: 18 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

| Intervention/Treatment |
| --- |
|Drug: Adalimumab|The loading dose will be 160 mg. A dose of 80 mg will be given at Week 2 and 40 mg every other week starting at Week 4 until completion at Week 24. If it is found that they are not responding to 40 mg of adalimumab at Week 8 or later, the dose may be increased to 40 mg weekly.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary pilot efficacy variable will be the induction of clinical response, which is defined as a decrease in Mayo score less than 30% from baseline or less than 3 points PLUS decrease in rectal bleeding sub-score less than or equal to 1 at week 8 |  | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission at each visit |  | 24 Weeks | 
| Clinical response at each visit |  | 24 Weeks | 
| Improvement in the mucosal inflammation at week 8 |  | 24 Weeks | 
| Mayo Score |  | 24 Weeks | 
| Ability to taper and discontinue steroids according to the tapering schedule after week 8 |  | 24 Weeks |