Treatment With Infliximab in a Medical Setting (Study P05587)
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Intervention: Infliximab 5 mg/kg; Infliximab 5 mg/kg every 6 weeks; Infliximab 7 mg/kg every 8 weeks
Intervention description: Participants received Infliximab 5 mg/kg intravenously (IV) at weeks 0, 2 and 6 during the induction phase. At Week 10, those who were in clinical response received further treatment every 8 weeks during the observational phase; Participants with loss of response in the observational phase were randomized at entry into the interventional phase received 5 mg/kg IV every 6 weeks (shortened interval group); Participants with loss of response in the observational phase were randomized at entry into the interventional phase received 7 mg/kg IV every 8 weeks (increased dose group)
Intervention MeSH terms: Infliximab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is an open-label, interventional study where a subset of participants will be randomized
      to one of two treatment-optimization strategies. Participants with moderate to severe Crohn's
      disease (CD) will receive induction treatment comprised of 3 infusions of infliximab at Weeks
      0, 2, and 6. The participants will be evaluated at Week 10. Participants who are in clinical
      response will enter the observational phase of the study where they will receive standard of
      care treatment, as per the infliximab product monograph. Participants who lose response, may
      qualify for entry into the interventional phase of the study, where they will be randomized
      to one of the following treatment-optimization arms: 1) dose increase: infliximab 7 mg/kg,
      every 8 weeks or 2) shortened interval: infliximab 5 mg/kg every 6 weeks.

      Note: Due to early study termination, no statistical analysis was performed for the
      interventional part of this study, therefore, endpoints dedicated to this phase of the study
      have not been analyzed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women >=18 years of age

          -  Moderate to severe CD (Crohn's Disease Activity Index [CDAI] >= 220 and <= 450)

          -  CD of at least 3 months duration confirmed within the past 2 years by radiography
             and/or endoscopy

          -  Biologic-naïve

          -  If using 5-Aminosalicylic Acid (5-ASA), there must be at least 4 weeks of stable
             dosage prior to screening

          -  If using azathioprine or 6-mercaptopurine, the start date must be at least 3 months
             prior to screening and the dose must be stable for at least 6 weeks prior to screening

          -  If using methotrexate, the participant must have been using methotrexate with a stable
             dosage of at least 6 weeks prior to screening

          -  Participants must be off corticosteroids or on a stable dose of corticosteroids for at
             least 2 weeks prior to enrollment. The maximal daily dose of corticosteroids at
             baseline must not exceed 30 mg of prednisone equivalent

          -  Participants are considered eligible according to the following tuberculosis (TB)
             screening criteria:

               -  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 study medication

               -  Within 3 months prior to the first administration of study medication, either
                  have negative OR have a newly identified positive diagnostic TB test result
                  (defined as at least 1 positive tuberculin skin 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 study medication

               -  Participants must have had a chest X-ray within 3 months prior to screening with
                  no evidence of current or old active TB

          -  Participants' screening and baseline clinical laboratory tests (complete blood count
             [CBC], blood chemistries, and urinalysis) must be within the following parameters:

               -  Hemoglobin >=10 g/dL (100 g/L)

               -  White blood cells (WBCs) >=3.5 x 109/L

               -  Neutrophils >=1.5 x 10^9/L

               -  Platelets >=100 x 10^9/L

               -  Serum creatinine <1.5 mg/dL (or <133 μmol/L)

               -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline
                  phosphatase, and gammaglutamyltransferase <=1.5 x upper limit of normal (ULN);

               -  Total bilirubin <=1 x ULN

          -  Antibiotics for the treatment of CD (e.g., ciprofloxacin and metronidazole) must have
             been discontinued at least 3 weeks prior to screening

          -  Participants must be free of any clinically significant condition or situation, other
             than CD that, in the opinion of the investigator, would interfere with the study
             evaluations or optimal participation in the study

          -  Participants are willing and able to adhere to the study visit schedule and other
             protocol requirements

          -  Participants are capable of providing written informed consent, which must be obtained
             prior to conducting any protocol-specified procedures

          -  Sexually-active women of child-bearing potential 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

          -  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-hCG) at screening

          -  have an increased Harvey-Bradshaw Index (HBI) score >=3 points over the week 10
             evaluation score and a CDAI score >=175

          -  have received regular infusions of Infliximab (IFX) every 8 weeks during the
             observational phase with a maximum interval of no more than 10 weeks between each
             infusions

          -  having previous doses of IFX of >= 4.7 mg/kg

        Exclusion Criteria:

          -  Are pregnant or plan to become pregnant during the study period; participants who are
             breast feeding

          -  Have been treated with excluded drugs prior to entry: any biological or anti- Tumor
             necrosis factor (anti-TNF) agent such as infliximab, adalimumab, certolizumab,
             etanercept, pentoxifylline, or thalidomide

          -  Have had a serious infectious disease in the 8 weeks prior to entry

          -  Have active perianal fistulas and a Perianal disease activity index (PDAI) score >10

          -  Have presumed fibro-stenotic stricture or acute bowel obstruction

          -  Have had live vaccination in the 6 weeks prior to entry

          -  Have known intolerance to study drug

          -  Have a history of myocardial infarction, congestive heart failure, coronary artery
             disease, or arrhythmias in the last 6 months

          -  Have a history of malignancy (within the past 5 years) with the exception of carcinoma
             in situ of the cervix or localized basal cell skin cancer that have been adequately
             treated

          -  Have a history of lymphoproliferative disease including lymphoma, or signs and
             symptoms suggestive of possible lymphoproliferative disease

          -  Have a history of demyelinating disease such as multiple sclerosis

          -  Have a positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV)
             surface antigen, or hepatitis C virus (HCV) antibody

          -  Have renal, hepatic, hematological, cardiovascular, pulmonary, neurological,
             psychiatric, immunologic, gastrointestinal, endocrine, or other diseases if they are
             clinically significant. (A clinically significant disease is defined as one which in
             the opinion of the investigator can put the participants at risk because of
             participation in the study or a disease which can influence the participant's ability
             to participate in the study or affect the results of the

        study)

          -  Have clinically significant abnormal laboratory test results, unless regarded by the
             investigator as related to CD

          -  Have a history of alcohol or drug abuse

          -  Are unable to comply with the protocol

          -  Have any clinically significant findings in the physical examination that, in the
             investigator's judgment, may interfere with the study evaluation or affect participant
             safety

          -  Are in a situation or condition that, in the opinion of the investigator, may
             interfere with optimal participation in the study

          -  Are participating in any other clinical study(ies) except for registries

          -  Are on the staff, affiliated with, or a family member of the staff personnel directly
             involved with this study

          -  Are allergic to or have sensitivity to the study drug or any of its excipients