A Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Patients With Moderately to Severely Active Crohn's Disease (IM-UNITI)
Condition: Crohn's Disease; Colitis; IBD; Inflammatory Bowel Disease
MeSH terms: Crohn Disease; Colitis; Inflammatory Bowel Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      The primary purpose of this study is to evaluate the efficacy and safety of 2 maintenance
      regimens of ustekinumab administered subcutaneously to patients with moderately to severely
      active Crohn's disease who responded to treatment with intravenous ustekinumab in studies
      CNTO1275CRD3001 and CNTO1275CRD3002, compared to subcutaneously administered placebo.
    

Detailed description: 
      The main purpose of this study is to determine whether additional ustekinumab treatment is
      beneficial in patients with moderately to severely active Crohn's disease who initially had a
      clinical response to IV ustekinumab in one of the 2 initial induction studies (the
      CNTO1275CRD3001 ["UNITI-1"] or CNTO1275CRD3002 ["UNITI-2"] induction studies). The
      maintenance treatment will be injections in the skin (given subcutaneously, or "SC") of 90 mg
      ustekinumab either every 8 weeks or 12 weeks, and the effects (both the benefits and any side
      effects or adverse events) will be compared to SC placebo injections (otherwise identical
      except without ustekinumab). Patients who responded to IV ustekinumab in the UNITI-1
      (NCT01369329) or UNITI-2 (NCT01369342) induction studies will be put into one of these 3
      groups by chance (randomly, like rolling dice). The study will be double-blinded (so that
      neither patients nor study personnel know the identity of the assigned treatment). Patients
      who are randomized to either SC placebo or 90mg ustekinumab SC every 12 weeks who experience
      worsening in their Crohn's Disease symptoms (per the study loss of response criteria) will
      have their treatment adjusted so that they will instead start to receive 90mg ustekinumab SC
      every 8 weeks. All patients from the UNITI-1 or UNITI-2 studies (in addition to the patients
      described above who responded to IV ustekinumab) will be eligible to enter this study,
      provided the Week 8 visit in those trials was completed and study requirements are still met.
      Patients who are not in clinical response to IV placebo or ustekinumab in UNITI-1 or UNITI-2
      will receive both IV and SC study agent at the first visit of this study (week 0). Patients
      previously receiving IV placebo will receive ustekinumab 130 mg IV at week 0 (and SC
      placebo), and patients previously receiving IV ustekinumab will receive 90 mg ustekinumab SC
      at week 0 (as well as IV placebo). If these patients are in clinical response 8 weeks later,
      they will receive 90 SC ustekinumab at that week8 visit, and will continue to receive
      Ustekinumab (every 8 weeks for participants not in response to IV Ustekinumab and every 12
      weeks for participants not in response to IV Placebo) throughout the rest of the study
      (provided they otherwise remain eligible). Patients in clinical response to IV placebo
      induction dosing will continue to receive SC placebo. The main part of this study, also
      called the maintenance portion, will last 44 weeks. After week 44, all participants who are
      continuing to do well will be eligible to continue to receive study agent in the second part
      of the study, a long term extension where the study agent will continue to be administered up
      to week 252. Participants who discontinue study agent, either during the study, or after week
      252, will be asked to return for a final safety follow-up visit 20 weeks after they last
      received study agent.

      Patients in response to IV ustekinumab will be randomized to receive either placebo (Group
      1), Ustekinumab 90 mg SC every 12 weeks (Group 2), or Ustekinumab 90mgSC every 8 weeks (Group
      3). If patients in Groups 1 or 2 lose response, they will cross over to receive ustekinumab
      90mg every 8 weeks. Other populations (nonresponders to prior IV ustekinumab or IV placebo)
      will receive ustekinumab at Week0 (either 90mg SC or 130mg IV, respectively) and continue SC
      ustekinumab if in response at Week 8, Placebo IV responders will continue to receive Placebo
      SC q4w.
    

Intervention name(s): Placebo SC; Placebo IV; Ustekinumab 90 mg SC q8w; Ustekinumab 130 mg IV; Ustekinumab 90 mg SC q12w
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Placebo will be administered subcutaneously.; Placebo will be administered as a single Intravenous infusion at week 0.; Ustekinumab 90 mg will be administered subcutaneously every 8 weeks (q8w) through Week 40.; Ustekinumab 130 mg will be administered as a single intravenous infusion at week 0.; Ustekinumab 90 mg will be administered as subcutaneously every 12 weeks (q12w) through Week 40.
Intervention MeSH terms: Ustekinumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Ustekinumab; Stelara, Moderately to severely active Crohn's Disease; IBD, Crohn's; UNITI; colitis; IL-12; IL-23