A Phase III, Multi-Center, Randomized, Placebo-Controlled Study to Evaluate theClinical Efficacy and Safety of Induction and Maintenance Therapy with Abatacept inSubjects with Active Ulcerative Colitis (UC) who have had an Inadequate ClinicalResponse and/or Intolerance to Medical Therapy.Revised Protocol 01, incorporating Protocol Amendment 02 (Version 1.0, Date 06-Dec-2006) and Administrative Letter 01.
- Conditions
- CERATIVE COLITIS,NOSMedDRA version: 8.1Level: LLTClassification code 10045365Term: Ulcerative colitis
- Registration Number
- EUCTR2006-003604-19-FR
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 978
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 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 corticosteroid treatment mu
-WOCBP unwilling or unable to use an acceptable method to avoid pregnancy for entire study period & for up to 10 weeks after study
-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
-History of cancer within last 5 years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to enrollment. Subjects with carcinoma in situ, treated with definitive surgical intervention, are allowed
-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)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 infections at time of potential enrollment, incl. subjects with evidence of HIV, Hepatitis B or HPC infection detected during screening
-Subjects with herpes zoster or CMV that resolved< 2 months prior to signing ICF
-Subject who received any live vaccines within 3 months of anticipated 1st dose of study medication or who will have need of a live vaccine at any time following entry in IP
-Clinically significant abnormal chest x-ray at screening
-Positive stool culture for enteric pathogens
-Stool positive for c. difficile toxin
Any of following lab values:
a)Hgb< 8.5 g/dL
b)WBC< 3,000/mm³ (3 x 109/L)
c)Platelets< 100,000
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method