Clinical trial NCT01369329: A Study to Evaluate the Safety and Efficacy of Ustekinumab in Patients With Moderately to Severely Active Crohn's Disease Who Have Failed or Are Intolerant to Tumor Necrosis Factor (TNF) Antagonist Therapy (UNITI-1)
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Subjects With Moderately to Severely Active Crohn's Disease Who Have Failed or Are Intolerant to TNF Antagonist Therapy (UNITI-1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn's Disease
IBD
Colitis
Inflammatory Bowel Disease
Keywords: ustekinumab
moderately to severely active Crohn's Disease
tumor necrosis factor, Stelara
Crohn
Crohn's
IBD
UNITI
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2011-06-08
Enrollment: 769
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study (UNITI-1) will compare the effects (both positive and negative) of an initial treatment with ustekinumab to placebo over 8 weeks, in patients with moderately to severely active Crohn's disease who have either failed or could not tolerate at least one TNF-antagonist medications in the past (specifically, infliximab, adalimumab, or certolizumab pegol).

Detailed description: This study (CNTO1275CRD3001 or "UNITI-1") examines ustekinumab (an antibody medication that inhibits the inflammatory proteins IL-12 and IL-23) versus a placebo (otherwise identical except without the ustekinumab antibody) given intravenously (by an IV) in adults with moderately to severely active Crohn's disease who previously did not respond to, lost response to, or could not tolerate TNF-antagonist medications (specifically, infliximab, adalimumab or certolizumab pegol). Ustekinumab (also known as Stelara) is approved as a treatment for the skin condition of moderate to severe plaque-type psoriasis, but this study will examine if ustekinumab can provide benefit in Crohn's disease and also assess for any risks or side effects. Both the positive and negative outcomes of IV placebo versus two different doses of IV ustekinumab will be tracked and compared over eight weeks, in approximately 703 patients. Patients enrolling in this study will be assigned to one of the 3 treatment groups by chance (randomly, like rolling dice), and all will receive a single IV administration of study agent at the first study visit (after the screening period), and then will be asked to return for 3 additional visits through Week 8. Patients who complete this study through the Week 8 visit and remain eligible can enter the maintenance study (CNTO1275CRD3003 or "IM-UNITI'' \[NCT01369355\]), where they will receive additional study agent, including the administration of ustekinumab in patients who receive placebo in this study and have not had improvement in their Crohn's disease. Patients who do not enter the CNTO1275CRD3003 study will have a final safety follow-up visit approximately 20 weeks after they received study agent when they entered into this study at the Week 0 visit. .All patients will receive a single intravenous (IV) administration of study drug (either placebo or ustekinumab) at the first (week 0) visit when they enter the study.There are 3 treatment groups: Group 1: Placebo; Group 2: ustekinumab 130 mg, Group 3: weight-range based ustekinumab doses approximating ustekinumab 6 mg/kg: 260 mg (weight \<= 55 kg), 390 mg (weight \> 55 kg and \<= 85 kg), and 520 mg (weight \> 85 kg).

Eligibility criteria: Inclusion Criteria:

* Have Crohn's disease of at least 3 months' duration with colitis, ileitis, or ileocolitis, confirmed at some time in the past by radiography, histology, or endoscopy
* Have active Crohn's disease, defined as a baseline Crohn's Disease Activity Index (CDAI) score of \>= 220 and \<= 450
* Have received infliximab, adalimumab, or certolizumab pegol at a dose approved for the treatment of Crohn disease and did not respond initially (ie, primary nonresponse)
* Or responded initially but then lost response with continued therapy (ie, secondary nonresponse)
* Or were intolerant to the medication
* Have screening laboratory test results within protocol-specified parameters.

Exclusion Criteria:

* Patients who have had any kind of bowel resection within 6 months
* Are pregnant or planning pregnancy (both men and women) while enrolled in the study or for 20 weeks after receiving study agent
* Patients who have received infliximab, adalimumab or certolizumab pegol \< = 8 weeks before the first administration of study drug
* Patients with certain complications of Crohn's disease that would make it hard to assess response to study drug
* Patients with a history of or ongoing chronic or recurrent infectious disease
* Patients who have previously received a biologic agent targeting IL-12 or IL-23, including but not limited to ustekinumab (CNTO 1275) or briakinumab (ABT-874)

Primary outcomes:
measure: Number of Participants With Clinical Response at Week 6
timeFrame: Baseline and Week 6
Secondary outcomes:
measure: Number of Participants in Clinical Remission at Week 8
timeFrame: Baseline and Week 8
measure: Number of Participants in Clinical Response at Week 8
timeFrame: Baseline and Week 8
measure: Number of Participants With Crohn's Disease Activity Index (CDAI) 70-point Response at Week 6
timeFrame: Baseline and Week 6
measure: Number of Participants With CDAI 70-point Response at Week 3
timeFrame: Baseline and Week 3
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: Little Rock
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state: Arkansas
city: La Jolla
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state: California
city: Los Angeles
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state: California
city: Redwood City
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state: California
city: San Carlos
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state: California
city: San Diego
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state: California
city: Lone Tree
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state: Colorado
city: New Haven
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state: Connecticut
city: Gainesville
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state: Florida
city: Jacksonville
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state: Florida
city: Weston
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state: Florida
city: Winter Park
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state: Georgia
city: Decatur
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state: Iowa
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city: Louisville
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state: Louisiana
city: New Orleans
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state: Louisiana
city: Baltimore
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state: Maryland
city: Chevy Chase
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state: Maryland
city: Towson
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state: Maryland
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state: Massachusetts
city: Worcester
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state: Massachusetts
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state: Michigan
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city: Morristown
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state: New Jersey
city: Great Neck
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city: Rochester
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city: Malvern
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city: St Poelten
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city: Wien
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city: Rio De Janeiro
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city: Montreal
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city: Hradec Kralove
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city: Usti Nad Labem
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city: Herlev
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country: Denmark
city: Amiens Cedex 1
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city: Caen
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country: France
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city: Nantes Cedex 1
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city: Paris Cedex 18
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country: France
city: Reims
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country: France
city: Toulouse
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city: Berlin
country: Germany
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country: Germany
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country: Germany
city: Hamburg
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city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Jena
country: Germany
city: Kiel
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city: Lÿneburg
country: Germany
city: Mannheim
country: Germany
city: Minden
country: Germany
city: München
country: Germany
city: Münster
country: Germany
city: Regensburg
country: Germany
city: Tübingen
country: Germany
city: Ulm
country: Germany
city: Szekszard
country: Hungary
city: Akureyri
country: Iceland
city: Reykjavik
country: Iceland
city: Dublin 9
country: Ireland
city: Dublin
country: Ireland
city: Jerusalem
country: Israel
city: Tel Hashomer
country: Israel
city: Chikushino
country: Japan
city: Fukuoka
country: Japan
city: Hamamatsu
country: Japan
city: Kagoshima
country: Japan
city: Nishinomiya
country: Japan
city: Ohtsu
country: Japan
city: Oita
country: Japan
city: Osaka
country: Japan
city: Sakura
country: Japan
city: Sapporo
country: Japan
city: Tokyo
country: Japan
city: Yokkaichi
country: Japan
city: Seoul
country: Korea, Republic of
city: Amsterdam
country: Netherlands
city: Maastricht
country: Netherlands
city: Rotterdam
country: Netherlands
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Grafton
country: New Zealand
city: Hamilton
country: New Zealand
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Belgrade
country: Serbia
city: Nis
country: Serbia
city: Cape Town
country: South Africa
city: Overport
country: South Africa
city: Madrid
country: Spain
city: Sagunto
country: Spain
city: Birmingham
country: United Kingdom
city: Brighton
country: United Kingdom
city: Bristol
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Exeter
country: United Kingdom
city: Gloucester
country: United Kingdom
city: Harrow
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
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: South Shields
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, Wong ECL, Dulai PS, Marshall JK, Jairath V, Reinisch W. Comparative Effectiveness of Biologics for Endoscopic Healing of the Ileum and Colon in Crohn's Disease. Am J Gastroenterol. 2022 Jul 1;117(7):1106-1117. doi: 10.14309/ajg.0000000000001795. Epub 2022 Apr 15.
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, 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: 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: 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.