Crohn's disease, NOS MedDRA version: 8.1 Level: LLT Classification code 10011401 Term: Crohn's disease
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 CD for at least 3 months from the time of initial diagnosis. Active CD must be confirmed by radiologic, endoscopic or histologic evidence within the previous 12 months. If previous confirmation of diagnosis is not available or if previous diagnosis is not deemed conclusive at time of screening, CD diagnosis should be confirmed by endoscopy, radiology or histology. 3) Subjects must satisfy at least one of the following criteria: a/ In the past had an inadequate response to at least 1 of the following treatments: i) oral prednisone >= 40 mg/day (or equivalent) or budesonide >= 9 mg/day for at least 2 weeks and/or ii) immunosuppressants (azathioprine >= 2 mg/kg/day or 6-mercaptopurine >= 1.0 mg/kg/day [or documentation of a therapeutic concentration of 6-thioguanine nucleotide] or methotrexate >= 15 mg/week) for at least 12 weeks and/or iii) an approved anti-TNF agent at an approved labeled dose for at least 8 weeks AND/OR b/ Have been intolerant to one of the above mentioned treatments (e.g., unable to 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 prednisone >= 20 mg/day (or equivalent) or budesonide >= 3 mg/day for at least 4 weeks and/or ii) 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 and tolerating the above mentioned treatments (with the exception of anti-TNF agents) should continue their treatment (see Drug Stabilization Requirements, 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 entry into the Induction Period. Acceptable documentation of inadequate response or intolerance in subjects include 1 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 CD therapy that is maintaining clinical remission, for the purpose of meeting eligibility requirements to enroll into this study. 4) Moderate to severe CD as measured by a CDAI score >= 220 and = Upper Limit of Normal (ULN) 6) Oral corticosteroid treatment must have been reduced to the equivalent of == 18 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years)
Exclusion criteria
Exclusion criteria: 1)WOCBP unwilling or unable to use an acceptable method to avoid pregnancy for entire study period & for up to 10 weeks after study 2)WOCBP using a prohibited contraceptive method 3)pregnant or breastfeeding women 4)Women with positive pregnancy test on enrollment or prior to study drug administration 5)Diagnosis of Ulcerative or Indeterminate Colitis 6)CD isolated to stomach, duodenum, jejunum, or perianal region without colonic or ileal involvement 7)Suspected or diagnosed intra-abdominal or perianal abscess at screening 8)Known strictures or stenosis (without inflammatory component) leading to symptoms or obstruction 9)Current evidence of fulminant colitis, toxic megacolon or bowel perforation 10)Current stoma or current need for colostomy or ileostomy. Use of seton for perianal disease 11)Previous total proctocolectomy or subtotal colectomy with ileorectal anastomosis 12)Surgical bowel resection <6 months before screening 13)Extensive small bowel resection or known short bowel syndrome 14)Primary sclerosing cholangitis 15)Currently receiving total parenteral nutrition 16)Past/current evidence of definite low grade or high grade colonic dysplasia 17)Subjects who are scheduled or anticipate the need for surgery aside from dermatologic procedures 18)History of clinically significant drug or alcohol abuse 19)Concomitant illness, likely to require systemic glucocorticosteroid therapy during study (e.g. moderate to severe asthma) 20)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 21)Subjects with a history or current evidence of malignancies; specifically subjects with a)history of cancer within last 5 years (other than NMSC 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 NMSC cancers which have been entirely removed prior to enrollment, or b)carcinoma in situ treated with definitive surgical intervention c)no evidence of malignancy upon completion of evaluation prompted by suspicious screening procedure. 22)Subjects at risk for tuberculosis 23)Subjects with any serious bacterial infection within last 3 months, unless treated & resolved with antibiotics, or any chronic bacterial infection 24)Female subjects who have had breast cancer screening that is suspicious for malignancy, & in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations (Protocol Section 7.3.2.4) 25)Subjects with evidence of active or latent bacterial or viral infections at the time of potential enrollment, including subjects with evidence of HIV, Hepatitis B or Hepatitis C infection detected during screening 26)Subjects with herpes zoster or cytomegalovirus that resolved <2 months before signing ICF 27)Subject who have received any live vaccines within 3 months of the anticipated first dose of study medication or who will have need of a live vaccine at any time following entry in Induction Period (IP) 28)Subject with a clinically significant abnormal chest x-ray at screening 29)Positive stool culture for enteric patho
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: * Placebo-Controlled Induction Period: Compare the proportion of subjects who have a clinical response (as defined by a reduction in Crohn’s Disease Activity Index [CDAI] >= 100 or an absolute CDAI score < 150) at both Day IP-57 (Week 8) and Day IP-85 (Week 12) between the abatacept and placebo treatment regimens. * Maintenance Period: Assess the proportion of subjects who are in clinical remission (CDAI < 150) at Day MP-365 (12 months) between the abatacept and placebo treatment regimens. * Open-label Extension Phase: Assess the long-term clinical safety and tolerability of abatacept treatment.;Secondary Objective: Induction Period (IP): -Compare proportion of subjects in clinical remission at both Day IP-57 & IP-85 between abatacept & placebo treatment regimens -Evaluate dose-response relationship by comparing proportions of subjects with a clinical response at both Day IP-57 & IP-85 induced by placebo & abatacept in increasing doses -Assess improvements in quality of life at Day IP-85 using the IBD Questionnaire in abatacept vs. placebo treated subjects Maintenance Period (MP): -Assess proportion of subjects between abatacept & placebo treatment regimens: • who have a clinical response at Day MP-365 • in clinical remission at both Day MP-169 & MP-365 -Assess in abatacept vs. placebo treated subjects improvements in quality of life using the SF-36 & IBD Questionnaire *IP+MP: Assess tolerability & safety of abatacept in subjects with CD Assess immunogenicity of abatacept in subjects with CD 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/~10mg/kg treatment regimen versus placebo and abatacept ~10mg/kg treatment regimen versus placebo who are in clinical response on Days IP-57 and IP-85. The Induction Period’s two primary comparisons will be te | — |
Countries
Belgium, Czech Republic, Denmark, France, Germany, Ireland, Italy, Netherlands, Poland, United Kingdom
Outcome results
None listed