A Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Patients With Moderately to Severely Active Crohn's Disease (IM-UNITI)

• ClinicalTrials.gov Identifier: NCT01369355
• Recruitment Status: Completed
• First Posted: June 8, 2011
• Results First Posted: February 23, 2017
• Last Update Posted: October 22, 2020
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: June 7, 2011
• First Posted Date: June 8, 2011
• Results First Submitted Date: October 17, 2016
• Results First Posted Date: February 23, 2017
• Last Update Posted Date: October 22, 2020
• Actual Study Start Date: September 13, 2011
• Actual Primary Completion Date: June 10, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 3, 2017)

Number of Participants With Clinical Remission at Week 44 [ Time Frame: Week 44 ]

Clinical remission at Week 44 was defined as a Crohn's Disease Activity Index (CDAI) score of <150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). CDAI was assessed by collecting information on 8 different Crohn's disease-related variables (extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being). A decrease in CDAI over time indicates improvement in disease activity.

• Original Primary Outcome Measures (submitted: June 7, 2011): Clinical remission [ Time Frame: at Week 44 ]

Current Secondary Outcome Measures (submitted: January 3, 2017)

• Number of Participants With Clinical Response at Week 44 [ Time Frame: Week 44 ]
  Clinical response at Week 44 was defined as a reduction from baseline in the Crohn's Disease Activity Index (CDAI) score of greater than or equal (>=) 100 points. Participants with a baseline CDAI score of > = 220 to less than or equal (< =) 248 were considered to be in clinical response if a CDAI score of less than (<) 150 was attained. A CDAI score of less than 150 indicates clinical remission. A decrease in CDAI score over time indicates improvement in disease activity.
• Number of Participants in Clinical Remission at Week 44 Among Participants in Clinical Remission to Ustekinumab at Week 0 of Maintenance Study [ Time Frame: Week 44 ]
  Clinical remission at week 44 was defined as a CDAI score of < 150 points among participants in clinical remission to ustekinumab at week 0 of maintenance study.
• Number of Participants With Corticosteroid-free Remission at Week 44 [ Time Frame: Week 44 ]
  Corticosteroid-free remission at Week 44 was defined as a CDAI score of <150 points without receiving corticosteroids at Week 44.
• Number of Participants in Clinical Remission at Week 44 in the Subset of Participants Who Were Refractory or Intolerant to Tumor Necrosis Factor (TNF) Antagonist Therapy [ Time Frame: Week 44 ]
  Clinical remission at Week 44 was defined as a CDAI score of <150 points in the subset of participants who were refractory or Intolerant to tumor necrosis factor antagonist therapy.

Original Secondary Outcome Measures (submitted: June 7, 2011)

• Remission in patient subgroups such as those in remission at Week 0 or those who previously failed TNF-antagonists (ie, patients entering from study CNTO1275CRD3001) [ Time Frame: at Week 44 ]
• Clinical response [ Time Frame: at Week 44 ]
• Corticosteroid-free remission [ Time Frame: at Week 44 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Patients With Moderately to Severely Active Crohn's Disease (IM-UNITI)
• Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Subjects With Moderately to Severely Active Crohn's Disease
• Brief 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Crohn's Disease
• Colitis
• IBD
• Inflammatory Bowel Disease

Intervention

• Drug: Placebo SC
  Placebo will be administered subcutaneously.
• Drug: Placebo IV
  Placebo will be administered as a single Intravenous infusion at week 0.
• Drug: Ustekinumab 90 mg SC q8w
  Ustekinumab 90 mg will be administered subcutaneously every 8 weeks (q8w) through Week 40.
• Drug: Ustekinumab 130 mg IV
  Ustekinumab 130 mg will be administered as a single intravenous infusion at week 0.
• Drug: Ustekinumab 90 mg SC q12w
  Ustekinumab 90 mg will be administered as subcutaneously every 12 weeks (q12w) through Week 40.

Study Arms

• Placebo Comparator: 001
  Participants who were responders to Intravenous (IV) infusion of ustekinumab induction will be randomized to receive a single dose of placebo subcutaneously (SC) every 4 weeks (q4w).
  Intervention: Drug: Placebo SC
• Experimental: 002
  Participants who were responders to IV ustekinumab induction will be randomized to receive a single dose of ustekinumab 90 milligram (mg) SC every 12 weeks (q12w).
  Intervention: Drug: Ustekinumab 90 mg SC q12w
• Experimental: 003
  Participants who were responders to IV ustekinumab induction will be randomized to receive a single dose of ustekinumab 90 mg SC every 8 weeks (q8w).
  Intervention: Drug: Ustekinumab 90 mg SC q8w
• Experimental: 004
  Participants who were nonresponders to IV ustekinumab induction will receive a single dose of ustekinumab 90 mg SC and one placebo IV at week 0, if then respond will continue to receive one ustekinumab 90 mg SC q8w.
  Interventions:

  • Drug: Placebo IV
  • Drug: Ustekinumab 90 mg SC q8w
• Experimental: 005
  Participants who were nonresponders to IV placebo induction will receive a single dose of ustekinumab 130 mg IV and one placebo SC at week 0, if then respond will continue to receive one ustekinumab 90 mg SC at week 8 then q12w.
  Interventions:

  • Drug: Placebo SC
  • Drug: Ustekinumab 130 mg IV
  • Drug: Ustekinumab 90 mg SC q12w
• Placebo Comparator: 006
  Participants who were responders to IV placebo induction will receive one dose of placebo SC q4w.
  Intervention: Drug: Placebo SC

Publications *

• Sandborn WJ, Feagan BG, Danese S, O'Brien CD, Ott E, Marano C, Baker T, Zhou Y, Volger S, Tikhonov I, Gasink C, Sands BE, Ghosh S. Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis of Results from Phase 2/3 Studies. Inflamm Bowel Dis. 2020 Sep 23. pii: izaa236. doi: 10.1093/ibd/izaa236. [Epub ahead of print]
• Li K, Friedman JR, Chan D, Pollack P, Yang F, Jacobstein D, Brodmerkel C, Gasink C, Feagan BG, Sandborn WJ, Rutgeerts P, De Hertogh G. Effects of Ustekinumab on Histologic Disease Activity in Patients With Crohn's Disease. Gastroenterology. 2019 Oct;157(4):1019-1031.e7. doi: 10.1053/j.gastro.2019.06.037. Epub 2019 Jul 4.
• Hanauer SB, Sandborn WJ, Feagan BG, Gasink C, Jacobstein D, Zou B, Johanns J, Adedokun OJ, Sands BE, Rutgeerts P, de Villiers WJS, Colombel JF, Ghosh S. IM-UNITI: Three-year Efficacy, Safety, and Immunogenicity of Ustekinumab Treatment of Crohn's Disease. J Crohns Colitis. 2020 Jan 1;14(1):23-32. doi: 10.1093/ecco-jcc/jjz110.
• Ghosh S, Gensler LS, Yang Z, Gasink C, Chakravarty SD, Farahi K, Ramachandran P, Ott E, Strober BE. Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's Disease: An Integrated Analysis of Phase II/III Clinical Development Programs. Drug Saf. 2019 Jun;42(6):751-768. doi: 10.1007/s40264-019-00797-3. Erratum in: Drug Saf. 2019 Apr 22;:.
• Rutgeerts P, Gasink C, Chan D, Lang Y, Pollack P, Colombel JF, Wolf DC, Jacobstein D, Johanns J, Szapary P, Adedokun OJ, Feagan BG, Sandborn WJ. Efficacy of Ustekinumab for Inducing Endoscopic Healing in Patients With Crohn's Disease. Gastroenterology. 2018 Oct;155(4):1045-1058. doi: 10.1053/j.gastro.2018.06.035. Epub 2018 Aug 29.
• Sandborn WJ, Rutgeerts P, Gasink C, Jacobstein D, Zou B, Johanns J, Sands BE, Hanauer SB, Targan S, Ghosh S, de Villiers WJS, Colombel JF, Feagan BG. Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy. Aliment Pharmacol Ther. 2018 Jul;48(1):65-77. doi: 10.1111/apt.14794. Epub 2018 May 24.
• Adedokun OJ, Xu Z, Gasink C, Jacobstein D, Szapary P, Johanns J, Gao LL, Davis HM, Hanauer SB, Feagan BG, Ghosh S, Sandborn WJ. Pharmacokinetics and Exposure Response Relationships of Ustekinumab in Patients With Crohn's Disease. Gastroenterology. 2018 May;154(6):1660-1671. doi: 10.1053/j.gastro.2018.01.043. Epub 2018 Feb 1.
• Hibi T, Imai Y, Murata Y, Matsushima N, Zheng R, Gasink C. Efficacy and safety of ustekinumab in Japanese patients with moderately to severely active Crohn's disease: a subpopulation analysis of phase 3 induction and maintenance studies. Intest Res. 2017 Oct;15(4):475-486. doi: 10.5217/ir.2017.15.4.475. Epub 2017 Oct 23.
• Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, Blank MA, Johanns J, Gao LL, Miao Y, Adedokun OJ, Sands BE, Hanauer SB, Vermeire S, Targan S, Ghosh S, de Villiers WJ, Colombel JF, Tulassay Z, Seidler U, Salzberg BA, Desreumaux P, Lee SD, Loftus EV Jr, Dieleman LA, Katz S, Rutgeerts P; UNITI-IM-UNITI Study Group. Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. N Engl J Med. 2016 Nov 17;375(20):1946-1960.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 5, 2017): 1282
• Original Estimated Enrollment (submitted: June 7, 2011): 1250
• Actual Study Completion Date: October 1, 2019
• Actual Primary Completion Date: June 10, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients who received study agent at the start of study CNTO1275CRD3001 or CNTO1275CRD3002 and completed the Week 8 visit. Exclusion Criteria:
• Patients who underwent a Crohn's disease-related surgery since the start of induction study CNTO1275CRD3001 or CNTO1275CRD3002
• Patients who started a protocol prohibited medication since the start of studies CNTO1275CRD3001 and CNTO1275CRD3002
• Patients with protocol-specified changes to their concomitant medications due to Crohn's disease (due to lack of efficacy) since the start of studies CNTO1275CRD3001 and CNTO1275CRD3002

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Croatia, Czechia, Denmark, France, Germany, Hungary, Iceland, Ireland, Israel, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Russian Federation, Serbia, South Africa, Spain, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01369355
• Other Study ID Numbers: CR018421; CNTO1275CRD3003 ( Other Identifier: Janssen Research & Development, LLC ); 2010-022760-12 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Janssen Research & Development, LLC
• Study Sponsor: Janssen Research & Development, LLC
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: September 2020