Safety/Efficacy Study of Bovine Intestinal Alkaline Phosphatase in Patients With Moderate to Severe Ulcerative Colitis

• Status: Completed
• Trial end date: 2006-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Ulcerative colitis is characterized by abnormal activation of, and damage to, the colon epithelium, which is considered to be a central pathogenic mechanism. Activation of colon epithelium cells in UC is associated with an abnormal high expression of Toll-like receptors, including TLR-4, the major transducer of LPS, binding specifically the lipid A portion of LPS. Alkaline Phosphatase binds and subsequently dephosphorylates LPS, thereby eliminating the ability of LPS to activate TLR-4. This is expected to 1) prevent activation of the intestinal epithelium and 2) prevent systemic inflammatory responses that result from transmigration of endotoxin though the leaky inflamed intestinal mucosa. Therefore, it is expected that administration of BIAP may attenuate or prevent the local and systemic inflammatory response in patients with severe ulcerative colitis.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AM-Pharma
• Collaborators: CRM Biometrics GmbH; Sintesi Research Srl; Vigilex BV

Criteria

Inclusion Criteria:

• Age, >18 years, AND

• Capable of understanding the purpose and risks of the study and have provided a signed and dated written IC, AND

• Prior to the study baseline, been treated with oral steroid medication, of which > 2 weeks on oral prednisone equivalent of at least 40mg/day, and still have:

• active ulcerative colon disease documented by a MAYO score of 6-11, and

• active ulcerative colon disease documented by a MTWSI score of 7-15

OR

• Prior to the study baseline, documented clinical inability to decrease or stop the course of oral steroid medication. Subjects have been treated for a minimum of 12 weeks, and still have:

• chronic active ulcerative colon disease documented by a MAYO score of 6-11, and

• chronic active ulcerative colon disease documented by a MTWSI score of 7-15

OR

• Prior to the study baseline, been treated with a stable dosage of azathioprine for a minimum of 12 weeks, and have a moderate to severe relapse defined as:

• chronic active ulcerative colon disease documented by a MAYO score of 6-11, and

• chronic active ulcerative colon disease documented by a MTWSI score of 7-15.

Exclusion Criteria:

• UC, requiring immediate surgical, endoscopic, or radiological intervention; including massive haemorrhage, perforation and sepsis, suppurative complications (intra-abdominal or peri-anal abscesses) or toxic colon,

• history of large bowel surgery,

• history of serious infections,

• positive stool cultures, including Clostridium difficile,

• significant organ dysfunction,

• pregnancy, nursing mothers, or women of childbearing potential without appropriate use of contraceptives,

• treatment with:

1. an altered dose of any 5-ASA preparation within 4 weeks of screening,

2. an altered dose of azathioprine or mercaptopurine within 4 weeks of screening (stable dosage of immunosuppressives is allowed), or start of azathioprine in the last 3 months prior to baseline,

3. probiotics, antibiotics within 1 month, methotrexate or cyclosporine within 2 months prior to screening,

4. any experimental treatment for this population e.g. infliximab, tacrolimus, FK506 or other anti TNFα therapy) within 2 months of screening.