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

NCT ID: NCT01369342

Last Updated: 2017-01-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

640 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-07-31

Study Completion Date

2014-10-31

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Crohn's Disease Inflammatory Bowel Disease IBD Colitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo IV

Group 1: Placebo Form=solution for injection route=intravenous use in a single dose.

Group Type PLACEBO_COMPARATOR

Group 1: Placebo

Intervention Type DRUG

Form=solution for injection, route=intravenous use, in a single dose.

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.

Group Type EXPERIMENTAL

Group 2 ustekinumab 130 mg

Intervention Type DRUG

Type=exact, unit=mg, number=130, form=solution for injection, route= intravenous use, in a single dose.

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).

Group Type EXPERIMENTAL

Group 3: ustekinumab approximately 6 mg/kg

Intervention Type DRUG

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).

Interventions

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Group 1: Placebo

Form=solution for injection, route=intravenous use, in a single dose.

Intervention Type DRUG

Group 2 ustekinumab 130 mg

Type=exact, unit=mg, number=130, form=solution for injection, route= intravenous use, in a single dose.

Intervention Type 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).

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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San Diego, California, United States

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Santa Monica, California, United States

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Torrance, California, United States

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Lone Tree, Colorado, United States

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Boca Raton, Florida, United States

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Gainesville, Florida, United States

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Jacksonville, Florida, United States

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Largo, Florida, United States

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Miami, Florida, United States

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Naples, Florida, United States

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Port Orange, Florida, United States

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Winter Park, Florida, United States

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Athens, Georgia, United States

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Atlanta, Georgia, United States

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Decatur, Georgia, United States

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Macon, Georgia, United States

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Idaho Falls, Idaho, United States

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Chicago, Illinois, United States

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Clive, Iowa, United States

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Pratt, Kansas, United States

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Topeka, Kansas, United States

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Crestview Hills, Kentucky, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Baton Rouge, Louisiana, United States

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Houma, Louisiana, United States

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New Orleans, Louisiana, United States

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Chevy Chase, Maryland, United States

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Columbia, Maryland, United States

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Towson, Maryland, United States

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Boston, Massachusetts, United States

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Worcester, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Chesterfield, Michigan, United States

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Novi, Michigan, United States

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Troy, Michigan, United States

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Ypsilanti, Michigan, United States

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Rochester, Minnesota, United States

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Jackson, Mississippi, United States

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Ocean Springs, Mississippi, United States

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Columbia, Missouri, United States

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Kansas City, Missouri, United States

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Lees Summit, Missouri, United States

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Urbana, Missouri, United States

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Las Vegas, Nevada, United States

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Egg Harbor, New Jersey, United States

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Marlton, New Jersey, United States

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Morristown, New Jersey, United States

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Great Neck, New York, United States

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New York, New York, United States

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Poughkeepsie, New York, United States

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Chapel Hill, North Carolina, United States

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Charlotte, North Carolina, United States

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Raleigh, North Carolina, United States

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Beavercreek, Ohio, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Mentor, Ohio, United States

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Norman, Oklahoma, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Bend, Oregon, United States

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Portland, Oregon, United States

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Malvern, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Columbia, South Carolina, United States

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North Charleston, South Carolina, United States

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Germantown, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Grapevine, Texas, United States

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Houston, Texas, United States

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Tyler, Texas, United States

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Salt Lake City, Utah, United States

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Charlottesville, Virginia, United States

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Chesapeake, Virginia, United States

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Virginia Beach, Virginia, United States

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Bellevue, Washington, United States

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Seattle, Washington, United States

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Madison, Wisconsin, United States

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Adelaide, , Australia

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Cairns, , Australia

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Central Queensland M C, , Australia

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Concord, , Australia

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Fremantle, , Australia

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Garran, , Australia

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Liverpool, , Australia

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Malvern, , Australia

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Parkville, , Australia

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Brussels, , Belgium

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Leuven, , Belgium

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Goiânia, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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Pleven, , Bulgaria

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Rousse, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Brandon, Manitoba, Canada

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Kingston, Ontario, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Saskatoon, Saskatchewan, Canada

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Saskatoon, , Canada

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Winnipeg, , Canada

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Osijek, , Croatia

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Rijeka, , Croatia

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Zagreb, , Croatia

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Amiens, , France

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Bordeaux, , France

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Caen, , France

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Lille, , France

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Paris, , France

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Rouen, , France

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Vandœuvre-lès-Nancy, , France

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Berlin, , Germany

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Bochum, , Germany

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Frankfurt, , Germany

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Halle, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Haßloch, , Germany

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Heidelberg, , Germany

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Kiel, , Germany

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Lÿneburg, , Germany

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Mannheim, , Germany

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Minden, , Germany

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München, , Germany

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Münster, , Germany

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Regensburg, , Germany

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Stade, , Germany

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Ulm, , Germany

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Békéscsaba, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Gyula, , Hungary

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Mosonmagyaróvár, , Hungary

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Pécs, , Hungary

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Szekszárd, , Hungary

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Székesfehérvár, , Hungary

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Reykjavik, , Iceland

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Beer Yaakov, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Petah Tikva, , Israel

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Rehovot, , Israel

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Tel Aviv, , Israel

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Chikushino-shi, , Japan

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Hachiōji, , Japan

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Hamamatsu, , Japan

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Hirosaki, , Japan

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Hiroshima, , Japan

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Kagoshima, , Japan

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Nishinomiya, , Japan

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Ohtsu, , Japan

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Osaka, , Japan

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Ōita, , Japan

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Sakura, , Japan

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Sapporo, , Japan

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Sendai, , Japan

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Suita-Shi, , Japan

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Tokyo, , Japan

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Tsu, , Japan

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Uruma, , Japan

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Yokkaichi, , Japan

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Yokohama, , Japan

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Yokosuka, , Japan

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Amsterdam, , Netherlands

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Amsterdam-Zuidoost, , Netherlands

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Maastricht, , Netherlands

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Rotterdam, , Netherlands

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Auckland, , New Zealand

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Christchurch, , New Zealand

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Dunedin, , New Zealand

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Grafton, , New Zealand

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Hamilton, , New Zealand

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Hastings, , New Zealand

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Plenty, , New Zealand

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Wellington, , New Zealand

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Bydgoszcz, , Poland

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Elblag, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Warsaw, , Poland

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Moscow, , Russia

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Novosibirsk, , Russia

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Belgrade, , Serbia

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Cape Town, , South Africa

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Durban, , South Africa

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Pretoria, , South Africa

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Daegu, , South Korea

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Gyeonggi-do, , South Korea

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Seoul, , South Korea

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Madrid, , Spain

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Sabadell, , Spain

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Santiago de Compostela, , Spain

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Birmingham, , United Kingdom

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Brighton, , United Kingdom

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Bristol, , United Kingdom

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Cambridge, , United Kingdom

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Gloucester, , United Kingdom

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Harrow, , United Kingdom

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Liverpool, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Norwich, , United Kingdom

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Nottinghamshirecc, , United Kingdom

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Oxford, , United Kingdom

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Shrewsbury, , United Kingdom

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Southampton, , United Kingdom

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Countries

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United States Australia Belgium Brazil Bulgaria Canada Croatia France Germany Hungary Iceland Israel Japan Netherlands New Zealand Poland Russia Serbia South Africa South Korea Spain United Kingdom

References

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Ghosh S, Feagan BG, Ott E, Gasink C, Godwin B, Marano C, Miao Y, Ma T, Loftus EV Jr, Sandborn WJ, Danese S, Abreu MT, Sands BE. Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis Through 5 Years in Crohn's Disease and 4 Years in Ulcerative Colitis. J Crohns Colitis. 2024 Aug 6;18(7):1091-1101. doi: 10.1093/ecco-jcc/jjae013.

Reference Type DERIVED
PMID: 38310565 (View on PubMed)

Colombel JF, Sands BE, Gasink C, Yeager B, Adedokun OJ, Izanec J, Ma T, Gao LL, Lee SD, Targan SR, Ghosh S, Hanauer SB, Sandborn WJ. Evolution of Symptoms After Ustekinumab Induction Therapy in Patients With Crohn's Disease. Clin Gastroenterol Hepatol. 2024 Jan;22(1):144-153.e2. doi: 10.1016/j.cgh.2023.06.014. Epub 2023 Jun 28.

Reference Type DERIVED
PMID: 37391056 (View on PubMed)

Dubinsky M, Ma C, Griffith J, Crowell M, Neimark E, Kligys K, O'Connell T. Matching-Adjusted Indirect Comparison Between Risankizumab and Ustekinumab for Induction and Maintenance Treatment of Moderately to Severely Active Crohn's Disease. Adv Ther. 2023 Sep;40(9):3896-3911. doi: 10.1007/s12325-023-02546-6. Epub 2023 Jun 27.

Reference Type DERIVED
PMID: 37368103 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36150926 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34077627 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32964215 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31279870 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30739254 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29909019 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29409871 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29142515 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27959607 (View on PubMed)

Other Identifiers

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CNTO1275CRD3002

Identifier Type: OTHER

Identifier Source: secondary_id

2010-022759-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR018418

Identifier Type: -

Identifier Source: org_study_id

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