ULCERATIVE COLITIS,NOS MedDRA version: 8.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed written informed consent 2) Subject must have had ulcerative colitis (UC) for at least 3 months from the time of initial diagnosis. The diagnosis of UC must have been confirmed by endoscopic and histologic evidence. If no previous confirmation of diagnosis is available or if previous diagnosis is not deemed conclusive, at time of screening endoscopy, histology should be performed to confirm diagnosis of UC 3) Subjects must satisfy one of the following criteria: a) In the past, had an inadequate response to one or more of the following treatments: i) Oral aminosalicylates (e.g. mesalamine, sulfasalazine, olsalazine, balsalizide) at or above the approved label dose for induction therapy for at least 6 weeks, and/or ii) Prednisone >= 40 mg/day (or equivalent) for at least 2 weeks, and/or iii) Immunosuppressants [azathioprine >= 2 mg/kg/day or 6-mercaptopurine >= 1.0 mg/kg/day, (or documentation of a therapeutic concentration of 6-thioguanine nucleotide)] for at least 12 weeks, and/or iv) An approved anti-TNF agent at an approved labeled dose for at least 8 weeks and/or v) Intravenous hydrocortisone >= 400 mg/day (or equivalent) for at least 1 week. AND/OR b) had been intolerant to one or more of the above mentioned treatments [e.g, unableto achieve doses or treatment durations because of dose limiting side effects (e.g. leukopenia, psychosis, uncontrolled diabetes, elevated liver enzymes)] AND/OR c) Currently receiving one or more of the following treatments: i) Oral aminosalicylates (e.g. mesalamine, sulfasalazine, olsalazine, balsalizide) at or above the approved label dose for at least 6 weeks and/or ii) Prednisone = 20 mg/day (or equivalent) for at least 4 weeks and/or iii) Immunosuppressants [azathioprine >= 2 mg/kg/day or 6-mercaptopurine >= 1.0 mg/kg/day, (or documentation of a therapeutic concentration of 6-thioguanine nucleotide)] for at least 12 weeks. Subjects currently receiving oral corticosteroids, oral aminosalicylates, azathioprine, or 6-mercaptopurine should continue their treatment (see Protocol Section 6.4.2.1). Subjects who had an inadequate response and/or intolerance to anti-TNF treatment must have had their last dose at least 8 weeks prior to the entry into the Induction Period. Subjects who had an inadequate response and/or intolerance to intravenous corticosteroid treatment must have had their last dose at least 4 weeks prior to entry into the Induction Period. Inadequate response and/or intolerance in the past (as defined above) will be assessed by the treating physician. Acceptable documentation of inadequate response or intolerance in subjects include one or more of the following: medical records; letters provided by the referring physician; other referral documents (e.g., insurance authorization forms), provided they contain the relevant information to support the subject’s ‘inadequate response’ and/or ‘intolerance’ to the designated therapy. In all circumstances, it should be established that discontinuation of the designated treatments was primarily due to lack of efficacy or intolerance (e.g., not due to unavailability of the drug). Subjects in clinical remission should not discontinue UC therapy that is maintaining clinical remission, for the purpose of meeting eligibility requirements to enroll into this study. 4) Subjects must have a Mayo score >= 6 and an endoscopic subscore of >= 2 5) Oral cortic
Exclusion criteria
Exclusion criteria: -WOCBP unwilling or unable to use an acceptable method to avoid pregnancy for entire study period & for up to 10 weeks after study (14 weeks for the European countries in which the European SmPC for Orencia™ IV is applicable) -WOCBP using prohibited contraceptive method -Pregnant or breastfeeding women -Women with positive pregnancy test on enrollment or prior to study drug administration -Diagnosis of Crohn’s Disease(CD), or Indeterminate Colitis or clinical findings suggestive of CD -Diagnosis of UC limited to rectum (ulcerative proctitis) -Current evidence of fulminant colitis, toxic megacolon or bowel perforation -Current need for colostomy or ileostomy -Previous total proctocolectomy or subtotal colectomy with ileorectal anastomosis, any surgical resection for UC -Surgical bowel resection within 6 months before screening for reasons other than UC -Primary sclerosing cholangitis(PSC) -Currently receiving total parenteral nutrition(TPN) -Required IV corticosteroids for UC 2 weeks before screening -Past or current evidence of definite colonic dysplasia -Subjects who are scheduled or anticipate need for surgery, aside from dermatologic procedures -Subjects with history of clinically significant drug or alcohol abuse -Concomitant illness likely to require systemic glucocorticosteroid therapy during study -Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, pulmonary, cardiac, neurological, ophthalmologic or cerebral disease Concomitant medical conditions that might place subject at unacceptable risk for participation in study -Subjects with a history or current evidence of malignancies; specifically, subjects with: a) a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection), or b) evidence of malignancies (including that detected by screening procedures), or c) signs of possible malignancies detected by screening procedures for which the workup to exclude malignancy has not been completed. The following subjects may be enrolled; those with: a) existing non-melanoma skin cell cancers which have been entirely removed prior to randomization, or b) carcinoma in situ, treated with definitive surgical intervention c) no evidence of malignancy upon completion of evaluation prompted by suspicious screening procedure -Subjects at risk for tuberculosis. Specifically, subjects with: a)history of active TB within last 3 years even if it was treated b)history of active TB >3 years ago unless there is documentation that prior anti-TB treatment was appropriate in duration & type c)Current clinical, radiographic or laboratory evidence of active TB d)Latent TB which was not successfully treated. Positive TB screening test indicative of latent TB would not be eligible unless active TB infection has been ruled out & they have initiated treatment for latent TB with isoniazid(INH) for at least 2 weeks prior to entry in Induction Period (IP) & they have negative chest x-ray at enrollment. Such subjects must complete 9 months of INH treatment -Subjects with any serious bacterial infection within last 3 months, unless treated & resolved with antibiotics, or any chronic bacterial infection -Female subjects who have had breast cancer screening suspicious for malignancy, & in whom possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations -Evidence of active or latent bacterial or viral i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: *Induction Period (IP): Compare the proportion of subjects in clinical response (defined as a reduction from baseline in Mayo score of >= 3 points and >= 30%, with an accompanying decrease from baseline in rectal bleeding subscore of >= 1 point or an absolute rectal bleeding subscore of == 3 points and >= 30%, with an accompanying decrease from baseline in rectal bleeding subscore of >= 1 point or an absolute rectal bleeding subscore of =< 1) at Month 12 (Day MP-365) between the abatacept and placebo treatment regimens. Open-Label Extension Phase (OL): Assess the long-term clinical safety and tolerability of abatacept treatment during the Open-Label Extension Phase.;Secondary Objective: IP: -Compare proportion of subjects between abatacept & placebo treatment regimens •in clinical remission at Week 12 •with mucosal healing at Week 12 -Evaluate dose-response relationship by comparing proportions of subjects in clinical response at Week 12 induced by placebo & abatacept in increasing doses -Assess in abatacept vs placebo treated subjects improvements in QoL as measured by IBDQ score at Week 12 MP: -Compare proportion of subjects between abatacept & placebo treatment regimens: •in clinical remission at Month 12 / at both Month 6 & 12 •with mucosal healing at Month 12 •using oral corticosteroids at baseline who discontinued corticosteroids & are in remission at Month 12 -Assess in abatacept vs placebo treated subjects improvements in QoL as measured by IBDQ score & SF-36 at Month 12 IP + MP: -Assess immunogenicity, tolerability & safety of abatacept in subjects with UC See Protocol Sections 2.1.2, 2.2.2, 2.3.2 for additional secondary objectives;Primary end point(s): * The Induction Period’s primary efficacy assessment will test for differences in the proportion of subjects in the Induction Period abatacept 30/~10 mg/kg treatment regimen versus placebo and abatacept ~10 mg/kg treatment regimen versus placebo in clinical response on Day IP-85. The In | — |
Countries
Belgium, Czech Republic, France, Germany, Ireland, Italy, Poland, United Kingdom
Outcome results
None listed