Conventional Step-Up Versus Infliximab Monotherapy in Patients With Ulcerative Colitis (P05553)
Condition: Colitis, Ulcerative
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: Infliximab; Prednisolone; 5-aminosalicylic acid; Azathioprine
Intervention description: Infliximab intravenous infusion at a dose of 5 mg/kg.; Oral prednisolone 40 mg/day or 1 mg/kg/day depending upon participant response.; 5-ASA administered orally at a dose of 2 g/day.; AZA administered orally at a dose of 2.0-2.5 mg/kg/day.
Intervention MeSH terms: Aminosalicylic Acid; Prednisolone; Infliximab; Mesalamine; Azathioprine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will be performed to compare the efficacy and safety of the classical "Step-Up"
      approach for treatment of moderate-to-severe active ulcerative colitis using oral
      prednisolone + oral 5-aminosalicylic acid (5-ASA) or oral prednisolone + oral azathioprine
      (AZA) with a more intensive and early "Top-Hold" approach with intravenous infliximab (5
      mg/kg) administered at Weeks 0, 2, and 6 and 8 weeks thereafter.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Any race or ethnicity

          -  Must have a diagnosis of moderate-to-severe active ulcerative colitis (UC) with
             inflammation present beyond the rectum and including more than 20 cm of the colon
             (Mayo score of 6 to 12 points, inclusive ≥ 2 in the endoscopy subscore)

          -  Must have responded inadequately to oral (with or without topical) 5-ASA treatment
             (prerequisite oral: at a minimum 4 g/d for 7 days) and must be considered for the
             first course of systemic corticosteroids; Participants with a UC and a Mayo score of ≥
             9 are also eligible without prior 5-ASA treatment

          -  Must agree to use acceptable methods of contraception for at least 2 weeks prior to
             starting any study treatment and to continue until at least 6 months after the last
             doses of study drugs

          -  Laboratory results must be within specified limits

          -  Must be negative for colorectal cancer or any associated lesions

          -  Must have a negative tuberculosis (TB) test

          -  Must have a chest x-ray within the 3 months with no clinically significant
             abnormality, or evidence of current active TB or latent TB

          -  Must have a negative stool culture

        Exclusion Criteria:

          -  Pregnant, nursing, or planning pregnancy

          -  Had received previous treatment for UC with the corticosteroids, infliximab,
             azathioprine/

             6-mercaptopurine (6-MP), cyclosporine, tacrolimus, methotrexate, sirolimus,
             mycophenolate, any tumor necrosis factor-alpha (TNF-α) inhibitor or receptor
             constructs that bind to ΤΝF-α (e.g., etanercept or adalimumab) and any other biologic
             agents

          -  Frequent (chronic) use of non-steroidal anti-inflammatory drugs (NSAIDs)

          -  Use of laxatives or any murine recombinant product

          -  Had surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction,
             or intra-abdominal or pancreatic abscess requiring surgical drainage in previous 2
             months

          -  History of colonic obstruction within the previous 6 months

          -  History of mucosal dysplasia, fistula or colonic resection, adenomatous polyps or
             stoma, severe, fixed symptomatic stenosis of the large or small intestine

          -  Had serious infection with previous 2 months, including human immunodeficiency virus
             (HIV) and hepatitis

          -  Had organ transplant (with the exception of a corneal transplant)

          -  Any malignancy within 5 years, including lymphoma

          -  History of demyelinating disease such as multiple sclerosis or optic neuritis

          -  Presence or history of congestive heart failure

          -  Requires chronic and frequent use of antimotility agents for control of diarrhea

          -  Requires total parenteral nutrition

          -  Had participated in any other clinical trial within 30 days or intention to
             participate in another clinical trial during participation in this study