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)

NCT ID: NCT01369329

Last Updated: 2016-12-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 769 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2013-07-31

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).

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

001

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.

002

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.

003

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

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

Group 1: Placebo

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

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Tucson, Arizona, United States

Little Rock, Arkansas, United States

La Jolla, California, United States

Los Angeles, California, United States

Redwood City, California, United States

San Carlos, California, United States

San Diego, California, United States

Lone Tree, Colorado, United States

New Haven, Connecticut, United States

Gainesville, Florida, United States

Jacksonville, Florida, United States

Weston, Florida, United States

Winter Park, Florida, United States

Atlanta, Georgia, United States

Decatur, Georgia, United States

Macon, Georgia, United States

Chicago, Illinois, United States

Evanston, Illinois, United States

Clive, Iowa, United States

Lexington, Kentucky, United States

Louisville, Kentucky, United States

Baton Rouge, Louisiana, United States

New Orleans, Louisiana, United States

Baltimore, Maryland, United States

Chevy Chase, Maryland, United States

Towson, Maryland, United States

Boston, Massachusetts, United States

Worcester, Massachusetts, United States

Ann Arbor, Michigan, United States

Chesterfield, Michigan, United States

Novi, Michigan, United States

Troy, Michigan, United States

Rochester, Minnesota, United States

Ocean Springs, Mississippi, United States

Lees Summit, Missouri, United States

Urbana, Missouri, United States

Las Vegas, Nevada, United States

Lebanon, New Hampshire, United States

Marlton, New Jersey, United States

Morristown, New Jersey, United States

Great Neck, New York, United States

New York, New York, United States

Rochester, New York, United States

Chapel Hill, North Carolina, United States

Charlotte, North Carolina, United States

Raleigh, North Carolina, United States

Beavercreek, Ohio, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Oklahoma City, Oklahoma, United States

Bend, Oregon, United States

Springfield, Oregon, United States

Hershey, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

North Charleston, South Carolina, United States

Nashville, Tennessee, United States

Austin, Texas, United States

Houston, Texas, United States

Tyler, Texas, United States

Salt Lake City, Utah, United States

Charlottesville, Virginia, United States

Chesapeake, Virginia, United States

Norfolk, Virginia, United States

Virginia Beach, Virginia, United States

Seattle, Washington, United States

Madison, Wisconsin, United States

Bedford Park, , Australia

Box Hill, , Australia

Central Queensland M C, , Australia

Concord, , Australia

Garran, , Australia

Liverpool, , Australia

Malvern, , Australia

Parkville, , Australia

Innsbruck, , Austria

Sankt Pölten, , Austria

Vienna, , Austria

Brussels, , Belgium

Leuven, , Belgium

Liège, , Belgium

Rio de Janeiro, , Brazil

Calgary, Alberta, Canada

Edmonton, Alberta, Canada

Vancouver, British Columbia, Canada

Brandon, Manitoba, Canada

Winnipeg, Manitoba, Canada

Hamilton, Ontario, Canada

Kingston, Ontario, Canada

London, Ontario, Canada

Montreal, Quebec, Canada

Hradec Králové, , Czechia

Ústí nad Labem, , Czechia

Herlev, , Denmark

Silkeborg, , Denmark

Amiens, , France

Caen, , France

Lille, , France

Marseille, , France

Nantes, , France

Paris, , France

Pessac, , France

Reims, , France

Rouen, , France

Toulouse, , France

Berlin, , Germany

Erlangen, , Germany

Essen, , Germany

Frankfurt, , Germany

Freiburg im Breisgau, , Germany

Halle, , Germany

Hamburg, , Germany

Hanover, , Germany

Heidelberg, , Germany

Jena, , Germany

Kiel, , Germany

Lÿneburg, , Germany

Mannheim, , Germany

Minden, , Germany

München, , Germany

Münster, , Germany

Regensburg, , Germany

Tübingen, , Germany

Ulm, , Germany

Szekszárd, , Hungary

Akureyri, , Iceland

Reykjavik, , Iceland

Dublin, , Ireland

Jerusalem, , Israel

Tel Litwinsky, , Israel

Chikushino-shi, , Japan

Fukuoka, , Japan

Hamamatsu, , Japan

Kagoshima, , Japan

Nishinomiya, , Japan

Ohtsu, , Japan

Osaka, , Japan

Ōita, , Japan

Sakura, , Japan

Sapporo, , Japan

Tokyo, , Japan

Yokkaichi, , Japan

Amsterdam, , Netherlands

Maastricht, , Netherlands

Rotterdam, , Netherlands

Auckland, , New Zealand

Christchurch, , New Zealand

Grafton, , New Zealand

Hamilton, , New Zealand

Krakow, , Poland

Lodz, , Poland

Belgrade, , Serbia

Niš, , Serbia

Cape Town, , South Africa

Overport, , South Africa

Seoul, , South Korea

Madrid, , Spain

Sagunto, , Spain

Birmingham, , United Kingdom

Brighton, , United Kingdom

Bristol, , United Kingdom

Cambridge, , United Kingdom

Cardiff, , United Kingdom

Exeter, , United Kingdom

Gloucester, , United Kingdom

Harrow, , United Kingdom

Liverpool, , United Kingdom

London, , United Kingdom

Manchester, , United Kingdom

Norwich, , United Kingdom

Nottinghamshirecc, , United Kingdom

Oxford, , United Kingdom

Shropshire, , United Kingdom

South Shields, , United Kingdom

Southampton, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Brazil; Canada; Czechia; Denmark; France; Germany; Hungary; Iceland; Ireland; Israel; Japan; Netherlands; New Zealand; Poland; Serbia; South Africa; South Korea; Spain; United Kingdom

References

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)

Huan PW, Mehta A, Wong ECL, Dulai PS, Marshall JK, Reinisch W, Narula N. A Review of the Modified Multiplier of Simple Endoscopic Score for Crohn's Disease and How to Use It in Clinical Trials and Practice. Am J Gastroenterol. 2025 Feb 25. doi: 10.14309/ajg.0000000000003373. Online ahead of print.

Reference Type: DERIVED

PMID: 39996607 (View on PubMed)

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)

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.

Reference Type: DERIVED

PMID: 35435862 (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

CNTO1275CRD3001

Identifier Type: OTHER

Identifier Source: secondary_id

2010-022758-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR018415

Identifier Type: -

Identifier Source: org_study_id