Efficacy & Safety of Infliximab Monotherapy Vs Combination Therapy Vs AZA Monotherapy in Ulcerative Colitis (Part 1) Maintenance Vs Intermittent Therapy for Maintaining Remission (Part 2)(Study P04807)

This is an interventional treatment trial for Ulcerative Colitis Read More

Inclusion Criteria:

• must be >=21 years of age at the time of informed consent, of either sex, and of any race;
• must have endoscopic evidence of UC, as determined by sigmoidoscopy, within 14 days prior to Baseline;
• must have a total Mayo score of 6 to 12 points at Baseline;
• must have responded inadequately to corticosteroid treatment (ie, the last or current UC flare did not respond adequately to a standard course of corticosteroids) with or without 5 aminosalicylic acid (5-ASA);
• must be off corticosteroids or on a stable dose of corticosteroid for at least 2 weeks prior to enrollment. The maximal daily dose of corticosteroid at Baseline must not exceed the equivalent of 30 mg of prednisone;
• must be naïve to infliximab and other tumor necrosis factor-alpha (TNF-α) antagonists;
• must be either naïve to AZA/6-MP or have not received AZA/6-MP for at least 3 months before enrollment in the study;

• considered eligible according to the following tuberculosis (TB) screening criteria:

  • have no history of latent or active TB prior to Screening;
  • have no signs or symptoms suggestive of active TB upon medical history and/or physical examination;
  • have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of IFX;
  • within 1 month prior to the first administration of infliximab, either have negative tuberculin skin test OR have a newly identified positive tuberculin test during Screening in which active TB has been ruled out, and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of IFX.
  • must have a chest X-ray (posterior-anterior and lateral views), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old active TB;
• have had UC for more than 10 years should have had a full colonoscopy within 2 years prior to Screening for the surveillance of dysplasia;
• screening and Baseline clinical laboratory tests (complete blood count [CBC] and blood chemistries) must be within predetermined parameters
• had been on antibiotics for the treatment of UC (eg, ciprofloxacin and metronidazole) must have been discontinued from them at least 3 weeks prior to Screening;
• must be free of any clinically significant condition or situation, other than UC that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study;
• willing and able to adhere to the study visit schedule and other protocol requirements;
• capable of providing written informed consent, which must be obtained prior to conducting any protocol-specified procedures;
• women of child-bearing potential and all men must agree to use a medically accepted method of contraception prior to screening, while receiving protocol-specified medication, and for 6 months after stopping the medication. Acceptable methods of contraception include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), oral or injectable hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation). Women of child-bearing potential who are not currently sexually active must agree to use a medically accepted method of contraception should they become sexually active while participating in the study;
• female participants of childbearing potential must have a negative serum pregnancy test (beta-human chorionic gonadotropin) at Screening and a negative urine pregnancy test at Baseline.

Exclusion Criteria:

• have severe extensive colitis as evidenced by:

  • investigator judgment that the participant is likely to require colectomy within 12 weeks of Baseline

OR

• at least 4 of these symptoms at Screening or Baseline visits, as follows:

  • diarrhea with >=6 bowel movements/day with macroscopic blood in stool;
  • focal severe or rebound abdominal tenderness;
  • persistent fever (>=37.5 degrees C) for at least 3 days prior to baseline;
  • tachycardia (>100 beats/minute);

  • hemoglobin <8.5 g/dL (5.3 mM/L).

    • require, or are required within the 2 months prior to baseline, surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage or other conditions possibly confounding the evaluation of disease activity;
    • have severe, fixed symptomatic stenosis of the large or small intestine;
    • have current evidence of colonic obstruction or history within the 6 months prior to baseline, confirmed with objective radiographic or endoscopic evidence of a stricture with resulting obstruction (dilation of the colon proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy);
    • have a history of colonic mucosal dysplasia;
    • presence on screening endoscopy of adenomatous colonic polyps, if not removed prior to study entry, or history of adenomatous colonic polyps that were not removed;
    • have the presence of a stoma;
    • have a history of extensive colonic resection that would prevent adequate evaluation of clinical disease activity (eg, less than 30 cm of colon remaining);
    • have had a positive stool culture for enteric pathogens, pathogenic ova or parasites within 4 months prior to Baseline unless participant has received treatment and had a negative stool examination 1 week or longer after the end of treatment;
    • have a concomitant diagnosis of congestive heart failure (CHF), including medically controlled asymptomatic subjects;
    • have had serious infections (eg, active hepatitis, pneumonia, or pyelonephritis) within 2 months of Screening. Less serious infections (such as acute upper respiratory tract infection [colds] or a simple urinary tract infection) need not be considered as an exclusion at the discretion of the investigator;
    • have had a nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months prior to Screening;
    • have a known infection with human immunodeficiency virus (HIV) and/or hepatitis B or hepatitis C;
    • have a history of a known allergy to murine proteins or allergy/sensitivity to study drug or its excipients;
    • have current signs and symptoms of systemic lupus erythematosus, or severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, or cerebral diseases;
    • have a known history of demyelinating disease suggestive of multiple sclerosis or optic neuritis;
    • presence of a transplanted organ (with the exception of a corneal transplant >3 months prior to Screening);
    • have a history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (eg, nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly;
    • have any current known malignancy or malignancy within 5 years prior to Screening (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence);
    • have poor tolerability of venipuncture or lack of adequate venous access for required blood sampling and infusion of study drug during the study period;
    • have had a known substance abuse or dependency (drug or alcohol) within 3 years of Screening;
    • require chronic (>=1 month) and frequent use (>=3 days per week)of nonsteroidal anti-inflammatory drugs (NSAIDs) except low-dose aspirin for prevention of heart attacks, unstable angina, or transient ischemic attacks;
    • have other inflammatory diseases that might interfere with the evaluation of the ulcerative colitis;
    • have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to Screening.
    • have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of Screening.
    • have had a chest X-ray within the 3 months prior to the first administration of study agent that shows an abnormality suggestive of malignancy or current active infection, including TB.
    • have received any specified prohibited treatment more recently than the indicated washout period prior to Screening;
    • who are participating in any other clinical study or who have received treatment with any investigational drug or device within 3 months prior Screening;
    • who is part of the staff or a family member of the staff personnel directly involved with this study.