Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year
Condition: Crohn Disease
MeSH terms: Crohn Disease
Intervention: Placebo for Ustekinumab; Placebo for Adalimumab; Ustekinumab (6 mg/kg); Ustekinumab (90 mg); Adalimumab (40 mg)
Intervention description: Participants will receive placebo as SC injection to blind adalimumab.; Participants will receive placebo as IV infusion to blind ustekinumab.; Participants will receive ustekinumab 6 mg/kg (weight based dosing) as IV infusion.; Participants will self-administer SC injection of ustekinumab 90 mg.; Participants will self-administer multiple SC injections of adalimumab (each 40 mg) and will receive total dose of 160 mg at Week 0, 80 mg at Week 2, and 40 mg q2w from Week 4 to 56.
Intervention MeSH terms: Adalimumab; Ustekinumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 386.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to compare the efficacy of treatment with ustekinumab or
      adalimumab in biologic naive participants with moderately-to-severely active Crohn's disease
      (CD) who have previously failed or were intolerant to conventional therapy (corticosteroids
      and/or immunomodulators, such as azathioprine, 6-mercaptopurine, or methotrexate), as
      measured by clinical remission at one year.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has Crohn's Disease (CD) or fistulizing CD of at least 3 months' duration, with
             colitis, ileitis, or ileocolitis, confirmed at some time in the past by radiography,
             histology, and/or endoscopy

          -  Has moderately-to-severely active CD with a baseline Crohn's disease activity index
             (CDAI) score of greater than or equal to (>=) 220 and less than or equal to (<=) 450

          -  Has one or more ulceration on screening ileocolonoscopy (which by definition, would
             result in an Simple Endoscopic Score for Crohn's Disease [SES-CD] of at least 3)

          -  Has failed or was intolerant to conventional therapy (corticosteroids, azathioprine
             [AZA], 6-mercaptopurine [6-MP] and/or methotrexate [MTX]) at adequate doses or is
             corticosteroid dependent

          -  Has not previously received an approved biologic for Crohn's Disease (i.e.,
             infliximab, adalimumab, certolizumab pegol, ustekinumab, natalizumab, vedolizumab or
             approved biosimilars of these agents)

          -  Participants on oral corticosteroids (e.g., prednisone, budesonide) at a
             prednisone-equivalent dose of <=40 or milligram/day (mg/day) or <=9 mg/day of
             budesonide are budesonide <=9 mg/day are permitted if doses are stable for 3 weeks
             prior to baseline

          -  Participants on AZA, 6-MP, or MTX at screening (or recently prior), must discontinue
             these medications at least 3 weeks prior to baseline

        Exclusion Criteria:

          -  Has complications of CD that are likely to require surgery or would confound the
             ability to assess the effect of ustekinumab or adalimumab treatment using the CDAI,
             such as: active stoma; short-gut syndrome and severe or symptomatic strictures or
             stenosis

          -  Currently has, or is suspected to have, an abscess. Recent cutaneous and perianal
             abscesses are not exclusionary if drained and adequately treated at least 3 weeks
             prior to baseline, or 8 weeks prior for intra-abdominal abscesses, if there is no
             anticipated need for any further surgery. Participants with active fistulas may be
             included if there is no anticipation of a need for surgery and there are currently no
             abscesses present

          -  Has had any kind of bowel resection within 6 months prior to baseline or other
             intra-abdominal surgery or a hospital admission for bowel obstruction within 3 months
             prior to baseline

          -  Has a stool culture or other examination positive for an enteric pathogen, including
             Clostridium difficile toxin, in the last 4 months unless a repeat examination is
             negative and there are no signs of ongoing infection with that pathogen

          -  Has received a Bacillus Calmette-Guerin (BCG) vaccination within 12 months or any
             other live bacterial or live viral vaccination within 2 weeks of baseline

          -  Has a history of, or ongoing, chronic or recurrent infectious disease, including but
             not limited to, chronic renal infection, chronic chest infection, recurrent urinary
             tract infection (eg, recurrent pyelonephritis or chronic nonremitting cystitis), or
             infected skin wounds or ulcers