Clinical trial NCT01369355: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn's Disease
Colitis
IBD
Inflammatory Bowel Disease
Keywords: Ustekinumab
Stelara, Moderately to severely active Crohn's Disease
IBD, Crohn's
UNITI
colitis
IL-12
IL-23
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2011-06-08
Enrollment: 1282
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Clinical Remission at Week 44
timeFrame: Week 44
Secondary outcomes:
measure: Number of Participants With Clinical Response at Week 44
timeFrame: Week 44
measure: Number of Participants in Clinical Remission at Week 44 Among Participants in Clinical Remission to Ustekinumab at Week 0 of Maintenance Study
timeFrame: Week 44
measure: Number of Participants With Corticosteroid-free Remission at Week 44
timeFrame: Week 44
measure: 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
timeFrame: Week 44
Other outcomes:
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city: Hirosaki
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country: Japan
city: Yokosuka
country: Japan
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city: Seoul
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city: Amsterdam
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country: Netherlands
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country: Netherlands
city: Auckland
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city: Christchurch
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city: Dunedin
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city: Hastings
country: New Zealand
city: Plenty
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country: Poland
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country: Poland
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country: Poland
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country: Poland
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Belgrade
country: Serbia
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country: South Africa
city: Cape Town
country: South Africa
city: Pretoria
country: South Africa
city: Somerset West
country: South Africa
city: Madrid
country: Spain
city: Birmingham
country: United Kingdom
city: Brighton
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city: Bristol
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city: Cambridge
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city: Exeter
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city: Gloucester
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city: London
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city: Manchester
country: United Kingdom
city: Norwich
country: United Kingdom
city: Nottinghamshirecc
country: United Kingdom
city: Oxford
country: United Kingdom
city: Shropshire
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Adedokun OJ, Xu Z, Gasink C, Kowalski K, Sandborn WJ, Feagan B. Population Pharmacokinetics and Exposure-Response Analyses of Ustekinumab in Patients With Moderately to Severely Active Crohn's Disease. Clin Ther. 2022 Oct;44(10):1336-1355. doi: 10.1016/j.clinthera.2022.08.010. Epub 2022 Sep 21.
citation: Narula N, Aruljothy A, Wong ECL, Homenauth R, Alshahrani AA, Marshall JK, Reinisch W. The impact of ustekinumab on extraintestinal manifestations of Crohn's disease: A post hoc analysis of the UNITI studies. United European Gastroenterol J. 2021 Jun;9(5):581-589. doi: 10.1002/ueg2.12094. Epub 2021 Jun 2.
citation: Sandborn WJ, Rebuck R, Wang Y, Zou B, Adedokun OJ, Gasink C, Sands BE, Hanauer SB, Targan S, Ghosh S, de Villiers WJS, Colombel JF, Feagan BG, Lynch JP. Five-Year Efficacy and Safety of Ustekinumab Treatment in Crohn's Disease: The IM-UNITI Trial. Clin Gastroenterol Hepatol. 2022 Mar;20(3):578-590.e4. doi: 10.1016/j.cgh.2021.02.025. Epub 2021 Feb 19.
citation: 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. 2021 Jun 15;27(7):994-1007. doi: 10.1093/ibd/izaa236.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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. doi: 10.1056/NEJMoa1602773.