A Randomized, Double-blind, Multiple Dose Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 181 in Subjects with Moderate to Severe Ulcerative Colitis
- Conditions
- inflammatory bowel diseaseUlcerative Colitis10017969
- Registration Number
- NL-OMON39233
- Lead Sponsor
- Amgen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 30
-Age 18 to 65 at screening (inclusive)
-Diagnosis of UC established >= 3 months before baseline by clinical and endoscopic evidence and corroborated by a histopathology report
-Moderate to severe active UC as defined by a total Mayo score of 6 to 12 with a centrally read rectosigmoidoscopy score >= 2 prior to baseline
-Demonstrated an inadequate response to, loss of response to, or intolerance to immunomodulators, anti-TNF agents or to corticosteroids (corticosteroids: non-US sites only)
-Subjects can be receiving the following treatments:
• Azathioprine or 6 mercaptopurine if treatment initiated at least 12 weeks prior to baseline and if stable dosage for >= 8 weeks prior to baseline
• Methotrexate up to 25 mg/week if stable dosage for >= 8 weeks prior to baseline
• 5 aminosalicylates and/or oral prednisone or equivalent up to 20 mg/day, if stable dosage for >= 2 weeks prior to baseline
-Neurological exam free of clinically significant, unexplained signs or symptoms in the opinion of the investigator during screening and no clinically significant change prior to randomization
-Subject has no known history of active tuberculosis
-Subject has a negative test for tuberculosis during screening
Disease Specific
-Disease limited to the rectum (ie, within 10 cm of the anal verge)
-Toxic megacolon
-Crohn*s Disease
-History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for UC
-Planned bowel surgery within 24 weeks from baseline
-Stool positive for C. Difficile toxin at screening
-History of gastrointestinal surgery within 8 weeks of baseline
-Primary Sclerosing Cholangitis ;Excluded Medications:
-Immunosuppressive therapy with either cyclosporine A, tacrolimus, or mycophenolate mofetil, within 1 month prior to baseline
-Prior exposure to anti TNF agents, within 2 months, or 5 times the respective elimination half life (whichever is longer) prior to baseline
-Any prior exposure to vedolizumab, rituximab, efalizumab, natalizumab
-Use of topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids within 2 weeks prior to baseline
-Use of intravenous corticosteroids within 2 weeks prior to screening and during screening
-Subject previously treated with AMG 181
-Subject who has received any type of live attenuated vaccine < 1 month prior to baseline or is planning to receive any such live attenuated vaccine over the course of the study
-Treatment of infection with intravenous (within 30 days of baseline) or oral (within 14 days prior to baseline) antibiotics, antivirals, or antifungals
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Remission at week 8 defined by a total Mayo Score <= 2 points, with no<br /><br>individual subscore > 1 point</p><br>
- Secondary Outcome Measures
Name Time Method <p>-Response at week 8 as defined by a decrease from baseline in the total Mayo<br /><br>Score of >= 3 points and >= 30%, with an accompanying decrease in the subscore<br /><br>for rectal bleeding of >= 1 point or an absolute subscore for rectal bleeding of<br /><br>0 or 1<br /><br>-Mucosal healing at week 8 as defined by an absolute subscore for<br /><br>rectosigmoidoscopy of 0 or 1<br /><br>-Sustained remission at both week 8 and week 24<br /><br><br /><br>Safety Endpoints:<br /><br>-Adverse events<br /><br>-Serious adverse events<br /><br>-Significant changes in laboratory values and vital signs<br /><br>-Anti AMG 181 antibodies</p><br>