A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Patients With Moderately to Severely Active Crohn's Disease (UNITI-2)

Study Description

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Brief Summary:

This study (UNITI-2) will compare the effects (both positive and negative) of an initial treatment with ustekinumab to a placebo over 8 weeks in patients with moderately to severely active Crohn's disease.

Condition or disease	Intervention/treatment	Phase
Crohn's Disease; Inflammatory Bowel Disease; IBD; Colitis	Drug: Group 1: Placebo; Drug: Group 2 ustekinumab 130 mg; Drug: Group 3: ustekinumab approximately 6 mg/kg	Phase 3

Detailed Description:

This study (CNTO1275CRD3002 or "UNITI-2") 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. 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 612 patients who have previously failed or were intolerant to corticosteroids or immunomodulators (methotrexate, azathioprine, or 6-mercaptopurine) or are dependent on corticosteroid medications. 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"), 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 (placebo or ustekinumab) at the start of the study.There are 3 treatment groups in this study: 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).

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	640 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
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 (UNITI-2)
Study Start Date :	July 2011
Actual Primary Completion Date :	August 2014
Actual Study Completion Date :	October 2014

Arms and Interventions

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Arm	Intervention/treatment
Placebo Comparator: Placebo IV; Group 1: Placebo Form=solution for injection route=intravenous use in a single dose.	Drug: Group 1: Placebo; Form=solution for injection, route=intravenous use, in a single dose.
Experimental: Ustekinumab 130 milligram (mg); Group 2 ustekinumab 130 mg Type=exact unit=mg number=130 form=solution for injection route= intravenous use in a single dose.	Drug: Group 2 ustekinumab 130 mg; Type=exact, unit=mg, number=130, form=solution for injection, route= intravenous use, in a single dose.
Experimental: Ustekinumab approximately (~) 6 milligram per kilogram (mg/kg); Group 3: ustekinumab approximately 6 mg/kg Type=range unit=mg/kg number=6 form=solution for injection route= intravenous use in a single dose.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).	Drug: Group 3: ustekinumab approximately 6 mg/kg; Type=range, unit=mg/kg, number=6, form=solution for injection, route= intravenous use, in a single dose.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).

Outcome Measures

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Primary Outcome Measures :

1. Number of Participants With Clinical Response at Week 6 [ Time Frame: Week 6 ]
   Clinical response at Week 6 was defined as a reduction from baseline in the Crohn's Disease Activity Index (CDAI) score of greater than or equal (>=) 100 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). 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 decrease in CDAI score over time indicates improvement in disease activity.

Secondary Outcome Measures :

1. Number of Participants in Clinical Remission at Week 8 [ Time Frame: Week 8 ]
   Clinical remission at Week 8 was defined as a Crohn's Disease Activity Index (CDAI) score of <150 points.
2. Number of Participants in Clinical Response at Week 8 [ Time Frame: Week 8 ]
   Clinical response at Week 8 was defined as a reduction from baseline in the CDAI score of greater than or equal (>=) 100 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). 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 decrease in CDAI score over time indicates improvement in disease activity.
3. Number of Participants With Crohn's Disease Activity Index (CDAI) 70 Point Response at Week 6 [ Time Frame: Week 6 ]
   70-point response is defined as at least 70 points reduction in CDAI score (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity.
4. Number of Participants With CDAI 70 Point Response at Week 3 [ Time Frame: Week 3 ]
   70-point response is defined as at least 70 points reduction in CDAI score (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 99 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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 Disease Activity Index (CDAI) score of >= 220 and <= 450, with confirmation of active inflammation
• Has failed conventional therapy as demonstrated by having received corticosteroids and/or immunomodulators(ie, AZA, MTX, or 6-MP) at adequate therapeutic doses OR Have a history of failure to respond to or tolerate an adequate course of corticosteroids and/or immunomodulators (ie, AZA, MTX, or 6-MP) at adequate therapeutic doses OR Is corticosteroid dependent or has had a history of corticosteroid dependency AND Has not previously demonstrated failure of or intolerance to 1 or more TNF-antagonist therapies (ie, infliximab, adalimumab, or certolizumab pegol) per study criteria
• 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)

Contacts and Locations

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  Show 224 Study Locations

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

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

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Adedokun OJ, Xu Z, Gasink C, Jacobstein D, Szapary P, Johanns J, Gao LL, Davis HM, Hanauer S, Feagan BG, Ghosh S, Sandborn WJ. Pharmacokinetics and Exposure Response Relationships of Ustekinumab in Patients With Crohn's Disease. Gastroenterology. 2018 Feb 1. pii: S0016-5085(18)30111-2. doi: 10.1053/j.gastro.2018.01.043. [Epub ahead of print]

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.

Responsible Party:	Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:	NCT01369342 History of Changes
Other Study ID Numbers:	CR018418; CNTO1275CRD3002 ( Other Identifier: Janssen Research & Development, LLC ); 2010-022759-42 ( EudraCT Number )
First Posted:	June 8, 2011
Results First Posted:	January 6, 2017
Last Update Posted:	January 6, 2017
Last Verified:	November 2016

Keywords provided by Janssen Research & Development, LLC:

ustekinumab; moderately to severely active Crohn's Disease; Stelara; IBD	colitis; crohn; UNITI; Crohn's

Additional relevant MeSH terms:

Crohn Disease; Ustekinumab; Colitis; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases	Digestive System Diseases; Intestinal Diseases; Colonic Diseases; Pharmaceutical Solutions; Dermatologic Agents