A Study to Evaluate Efficacy and Safety of Ustekinumab Re-induction Therapy in Participants With Moderately to Severely Active Crohn's Disease
Condition: Crohn Disease
MeSH terms: Crohn Disease
Intervention: Ustekinumab approximately 6 mg/kg (IV); Placebo (SC); Placebo (IV); Ustekinumab 90 mg (SC) Group 1; Ustekinumab 90 mg (SC) Group 2
Intervention description: Participants will receive ustekinumab approximately 6mg/kg intravenously at Week 0.; Participants will receive SC injection of placebo at Week 0.; Participants will receive IV infusion of placebo at Week 0.; Participants will receive SC injection of ustekinumab 90 mg at Weeks 8 and 16.; Participants will receive SC injection of ustekinumab 90 mg at Weeks 0, 8 and 16.
Intervention MeSH terms: 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: 215.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary purpose of this study is to evaluate the efficacy and safety of a single
      intravenous (IV) re-induction dose of approximately 6 milligram per kilogram (mg/kg)
      ustekinumab in participants with secondary loss of response (LoR) to subcutaneous (SC) every
      8 Weeks (q8w) 90 mg ustekinumab maintenance therapy.
    

Eligibility criteria:

        Inclusion criteria:

          -  A history of Crohn's disease or fistulizing Crohn's disease of at least 3 months'
             duration, with colitis, ileitis, or ileocolitis, confirmed at any time in the past by
             radiography, histology, and/or endoscopy

          -  Currently receiving subcutaneous 90 mg every 8 weeks (q8w) ustekinumab maintenance
             therapy and initially responded to ustekinumab induction therapy, administered
             according to the local label, followed by secondary loss of response (LoR) to
             ustekinumab. Secondary LoR to ustekinumab is defined as active disease at study
             baseline, proven by a Crohn's Disease Activity Index (CDAI) score of greater than or
             equal to (>=) 220 and <=450 with at least one of the following: Elevated C-reactive
             protein (CRP) (>3.0 milligram per liter [mg/L]); and/or elevated Fecal calprotectin
             (fCal) >250 milligram per kilogram [mg/kg]); and/or endoscopy (performed less than or
             equal to (<=) 3 months before baseline) with evidence of active Crohn's disease,
             (defined as one or more ulcerations in the ileum and/or colon)

          -  Participants receiving either oral 5-aminosalicylic acid (5-ASA) compounds, oral
             corticosteroids (for example {e.g.}, prednisone, budesonide) at a
             prednisone-equivalent dose of <=40 mg/day or <=9 mg/day of budesonide, antibiotics
             used as the primary treatment of Crohn's disease, or conventional immunomodulators
             (i.e., azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]) are
             permitted providing the doses indicated are stable before baseline or have been
             discontinued before baseline within the protocol defined durations

        Exclusion Criteria:

          -  Complications of Crohn's disease, such as symptomatic strictures or stenoses, short
             gut syndrome, or any other manifestation that might be anticipated to require surgery,
             could preclude the use of the CDAI to assess response to therapy, or would possibly
             confound the ability to assess the effect of treatment with ustekinumab

          -  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
             before baseline (or 8 weeks before baseline for intra-abdominal abscesses) provided
             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 identified

          -  Any kind of bowel resection within 6 months or any other intra-abdominal surgery
             within 3 months before baseline

          -  A draining (i.e., functioning) stoma or ostomy

          -  Received ustekinumab intravenous re-induction after the initial weight-tiered-based IV
             induction dose of ustekinumab

          -  Any known history of shortened frequency of SC dose administration (<q8w) for a
             secondary loss of response where the participant did not, in the opinion of the
             treating physician, benefit from the dose interval shortening