A Study of Safety and Effectiveness of Ustekinumab in Patients With Moderate to Severe Active Crohn's Disease Who Have Been Previously Treated With Anti-TNF Therapy

NCT ID: NCT00771667

Last Updated: 2013-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 526 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2010-12-31

Brief Summary

A medical research study in adult patients who have moderate to severe Crohn's disease designed to determine whether or not treatment with an experimental drug called ustekinumab (or CNTO1275) is safe or not and to determine if the treatment will reduce the symptoms of Crohn's disease.

Detailed Description

In Crohn's disease there is inflammation (changes in body tissue which normally happen during injury or infection) and or ulceration (open sores) in the intestines.This occurs because the immune system (the part of the body that fights off infection) has an abnormal and overactive response against the intestine and bowel tissues of the body. Crohn's disease is usually treated with medications that either directly decrease inflammation or decrease the general activity of the immune system to improve the diarrhea, abdominal pain, and other symptoms of Crohn's Disease. Ustekinumab antibodies (natural substances made by your immune system to stick to and help remove foreign materials in your body that cause diseases) have been created to stick to and block the activity of two of the immune substances thought to cause abnormal inflammation of Crohn's disease. Patients who are eligible and who have received Remicade, Humira, or Cimzia and failed or been intolerant to one of these drugs will be randomized to either active drug (ustekinumab) or placebo. All patients will be randomized (like flipping a coin) at week 0 to be in one of 4 groups. At week 0 the study drug will be given by IV administration and at weeks 8 and 16 by subcutaneous injection. There will be 11 study visits in total and the study will continue until week 36. Blood and stool samples will be collected and studied, questionnaires to check on how you are doing in terms of your disease will be completed, an Electrocardiogram (EKG) obtained, safety evaluations conducted and diary cards distributed to be completed during the entire study. One of 4 groups: Grp 1-placebo, Grp 2-active drug 1mg/kg IV, Grp 3-active drug 3mg/kg IV, Grp 4-active drug 6mg/kg IV. Based on the clinical response status at Week 6, patients from Grps 2, 3 and 4 will be re-randomized at week 8 to receive either placebo or 90 mg SC at both weeks 8 and 16 and patients from Grp 1 will receive placebo at Week 8 and Week 16 or a 270 mg SC injection at Week 8 and 90 mg SC at Week 16.

Conditions

Crohn's Disease

Study Design

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

Study Groups

Placebo (IP)

Group Type: PLACEBO_COMPARATOR

Placebo (IP)

Intervention Type: DRUG

Induction phase (Week 0-8) (IP) - Placebo IV group

Ustekinumab 1mg/kg (IP)

Group Type: EXPERIMENTAL

Ustekinumab 1mg/kg (IP)

Intervention Type: DRUG

Induction phase (Week 0-8) (IP) - Ustekinumab 1 mg/kg IV group

Ustekinumab 3 mg/kg (IP)

Group Type: EXPERIMENTAL

Ustekinumab 3 mg/kg (IP)

Intervention Type: DRUG

Induction phase (Week 0-8) (IP) - Ustekinumab 3mg/kg IV group

Ustekinumab 6 mg/kg (IP)

Group Type: EXPERIMENTAL

Ustekinumab 6 mg/kg (IP)

Intervention Type: DRUG

Induction phase (Week 0-8) (IP) - Ustekinumab 6mg/kg IV group

Placebo IV - Responder - Placebo SC (MP)

Group Type: PLACEBO_COMPARATOR

Placebo IV - Responder - Placebo SC (MP)

Intervention Type: DRUG

Maintenance phase (Week 8-36) (MP) - Receiving Placebo IV at Week 0 - Responder at week 6 - Receiving Placebo SC at Week 8 and Week 16

Placebo IV - Nonresponder - Ustekinumab 270/90 mg SC

Group Type: PLACEBO_COMPARATOR

Placebo IV - Nonresponder - Ustekinumab 270/90 mg SC (MP)

Intervention Type: DRUG

Maintenance phase (Week 8-36) (MP) - Receiving Placebo IV at Week 0 - Nonresponder at week 6 - Receiving Ustekinumab 270 mg SC at Week 8 and 90 mg at Week 16

Ustekinumab IV - Responder - Placebo SC (MP)

Group Type: PLACEBO_COMPARATOR

Ustekinumab IV - Responder - Placebo SC (MP)

Intervention Type: DRUG

Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Responder at week 6 - Receiving Placebo SC at Week 8 and Week 16

Ustekinumab IV - Responder - Ustekinumab 90mg SC (MP)

Group Type: EXPERIMENTAL

Ustekinumab IV - Responder - Ustekinumab 90mg SC (MP)

Intervention Type: DRUG

Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Responder at week 6 - Receiving Ustekinumab 90 mg SC at Week 8 and Week 16

Ustekinumab IV - Nonresponder - Placebo SC (MP)

Group Type: PLACEBO_COMPARATOR

Ustekinumab IV - Nonresponder - Placebo SC (MP)

Intervention Type: DRUG

Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Nonresponder at week 6 - Receiving Placebo SC at Week 8 and Week 16

Ustekinumab IV - Nonresponder - Ustekinumab 90mg SC (MP)

Group Type: EXPERIMENTAL

Ustekinumab IV - Nonresponder - Ustekinumab 90mg SC (MP)

Intervention Type: DRUG

Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Nonresponder at week 6 - Receiving Ustekinumab 90 mg SC at Week 8 and Week 16

Interventions

Placebo (IP)

Induction phase (Week 0-8) (IP) - Placebo IV group

Intervention Type: DRUG

Ustekinumab 1mg/kg (IP)

Induction phase (Week 0-8) (IP) - Ustekinumab 1 mg/kg IV group

Intervention Type: DRUG

Ustekinumab 3 mg/kg (IP)

Induction phase (Week 0-8) (IP) - Ustekinumab 3mg/kg IV group

Intervention Type: DRUG

Ustekinumab 6 mg/kg (IP)

Induction phase (Week 0-8) (IP) - Ustekinumab 6mg/kg IV group

Intervention Type: DRUG

Placebo IV - Responder - Placebo SC (MP)

Maintenance phase (Week 8-36) (MP) - Receiving Placebo IV at Week 0 - Responder at week 6 - Receiving Placebo SC at Week 8 and Week 16

Intervention Type: DRUG

Placebo IV - Nonresponder - Ustekinumab 270/90 mg SC (MP)

Maintenance phase (Week 8-36) (MP) - Receiving Placebo IV at Week 0 - Nonresponder at week 6 - Receiving Ustekinumab 270 mg SC at Week 8 and 90 mg at Week 16

Intervention Type: DRUG

Ustekinumab IV - Responder - Placebo SC (MP)

Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Responder at week 6 - Receiving Placebo SC at Week 8 and Week 16

Intervention Type: DRUG

Ustekinumab IV - Responder - Ustekinumab 90mg SC (MP)

Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Responder at week 6 - Receiving Ustekinumab 90 mg SC at Week 8 and Week 16

Intervention Type: DRUG

Ustekinumab IV - Nonresponder - Placebo SC (MP)

Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Nonresponder at week 6 - Receiving Placebo SC at Week 8 and Week 16

Intervention Type: DRUG

Ustekinumab IV - Nonresponder - Ustekinumab 90mg SC (MP)

Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Nonresponder at week 6 - Receiving Ustekinumab 90 mg SC at Week 8 and Week 16

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Must have Crohn's disease or fistulizing Crohn's disease of at least 3 months duration
• Must have received Remicade, adalimumab or Cimzia at a dose approved for the treatment of Crohn's disease
• Must have failed or been intolerant to Remicade, Humira or Cimzia for treatment of Crohn's disease
• Must be 18 years of age or older
• Must have active Crohn's disease according to the Crohn's Disease Activity Index (CDAI > =220 and < =450).

Exclusion Criteria

• Patients who have had any kind of bowel resection, diversions or placement of a stoma within 6 months
• Are pregnant, nursing or planning pregnancy (both men and women) while enrolled in the study or within 1 year after receiving study agent
• Patients who have received Remicade, Humira or Cimzia < =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.

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

Sponsors

Centocor, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Janssen R&D US

Principal Investigators

Centocor, Inc. Clinical Trial

Role: STUDY_DIRECTOR

Centocor, Inc.

Locations

Mobile, Alabama, United States

Scottsdale, Arizona, United States

La Jolla, California, United States

Los Angeles, California, United States

Roseville, California, United States

San Carlos, California, United States

San Francisco, California, United States

Englewood, Colorado, United States

Lakewood, Colorado, United States

Littleton, Colorado, United States

Hamden, Connecticut, United States

Gainesville, Florida, United States

Hollywood, Florida, United States

Jacksonville, Florida, United States

Miami, Florida, United States

Naples, Florida, United States

Panama City, Florida, United States

Pembroke Pines, Florida, United States

Port Charlotte, Florida, United States

Port Orange, Florida, United States

South Miami, Florida, United States

Tampa, Florida, United States

Vero Beach, Florida, United States

Winter Park, Florida, United States

Zephyrhills, Florida, United States

Atlanta, Georgia, United States

Columbus, Georgia, United States

Decatur, Georgia, United States

Macon, Georgia, United States

Newnan, Georgia, United States

Arlington Heights, Illinois, United States

Chicago, Illinois, United States

Evanston, Illinois, United States

Indianapolis, Indiana, United States

Clive, Iowa, United States

Pratt, Kansas, United States

Lexington, Kentucky, United States

Louisville, Kentucky, United States

Baltimore, Maryland, United States

Chevy Chase, Maryland, United States

Towson, Maryland, United States

Boston, Massachusetts, United States

Burlington, Massachusetts, United States

Worcester, Massachusetts, United States

Ann Arbor, Michigan, United States

Chesterfield, Michigan, United States

Detroit, Michigan, United States

Troy, Michigan, United States

Rochester, Minnesota, United States

Ocean Springs, Mississippi, United States

Mexico, Missouri, United States

Lebanon, New Hampshire, United States

Egg Harbor, New Jersey, United States

Great Neck, New York, United States

New York, New York, United States

Poughkeepsie, New York, United States

Setauket, New York, United States

Stony Brook, New York, United States

Chapel Hill, North Carolina, United States

Charlotte, North Carolina, United States

Greenville, North Carolina, United States

Kinston, North Carolina, United States

New Bern, North Carolina, United States

Raleigh, North Carolina, United States

Beavercreek, Ohio, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Dayton, Ohio, United States

Oklahoma City, Oklahoma, United States

Philadelphia, Pennsylvania, United States

Charleston, South Carolina, United States

Columbia, South Carolina, United States

Chattanooga, Tennessee, United States

Nashville, Tennessee, United States

Austin, Texas, United States

Houston, Texas, United States

Lewisville, Texas, United States

San Antonio, Texas, United States

Ogden, Utah, United States

Salt Lake City, Utah, United States

Burlington, Vermont, United States

Charlottesville, Virginia, United States

Norfolk, Virginia, United States

Bellevue, Washington, United States

Lakewood, Washington, United States

Seattle, Washington, United States

Tacoma, Washington, United States

Madison, Wisconsin, United States

Adelaide, , Australia

Bankstown, , Australia

Bedford Park, , Australia

Box Hill, , Australia

Concord, , Australia

East Melbourne, , Australia

Fitzroy, , Australia

Frankston, , Australia

Fremantle, , Australia

Garran, , Australia

Herston, , Australia

Parkville, , Australia

Prahran, , Australia

South Brisbane, , Australia

Innsbruck, , Austria

Linz, , Austria

Salzburg, , Austria

Vienna, , Austria

Bonheiden, , Belgium

Brussels, , Belgium

Edegem, , Belgium

Kortrijk, , Belgium

Leuven, , Belgium

Liège, , Belgium

Roeselare, , Belgium

Calgary, Alberta, Canada

Edmonton, Alberta, Canada

Vancouver, British Columbia, Canada

Victoria, British Columbia, Canada

Hamilton, Ontario, Canada

London, Ontario, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Québec, Quebec, Canada

Saskatoon, Saskatchewan, Canada

Amiens Cedex 1 80, , France

Grenoble, , France

Lille, , France

Nice, , France

Paris, , France

Pessac, , France

Rouen, , France

Toulouse Cedex 9 N/A, , France

Berlin, , Germany

Hamburg, , Germany

Hanover, , Germany

Kiel, , Germany

Leipzig, , Germany

Lÿneburg, , Germany

Markkleeberg, , Germany

Minden, , Germany

München, , Germany

Münster, , Germany

Regensburg, , Germany

Afula, , Israel

Beersheba, , Israel

Haifa, , Israel

Jerusalem, , Israel

Kfar Saba, , Israel

Petah Tikva, , Israel

Tel Aviv, , Israel

Amersfoort, , Netherlands

Amsterdam, , Netherlands

Leiden, , Netherlands

Maastricht, , Netherlands

Rotterdam, , Netherlands

Auckland, , New Zealand

Christchurch, , New Zealand

Barcelona, , Spain

Córdoba, , Spain

León, , Spain

Madrid, , Spain

Oviedo, , Spain

Palma, , Spain

Sabadell, , Spain

Zaragoza, , Spain

Bristol, , United Kingdom

Cambridge, , United Kingdom

Coventry, , United Kingdom

Edinburgh, , United Kingdom

Harrow, , United Kingdom

London, , United Kingdom

Manchester, , United Kingdom

Newcastle upon Tyne, , United Kingdom

Norwich, , United Kingdom

Nottinghamshirecc, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; France; Germany; Israel; Netherlands; New Zealand; 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)

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)

Di Narzo AF, Telesco SE, Brodmerkel C, Argmann C, Peters LA, Li K, Kidd B, Dudley J, Cho J, Schadt EE, Kasarskis A, Dobrin R, Hao K. High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors. PLoS Genet. 2017 Jan 27;13(1):e1006565. doi: 10.1371/journal.pgen.1006565. eCollection 2017 Jan.

Reference Type: DERIVED

PMID: 28129359 (View on PubMed)

Sandborn WJ, Gasink C, Gao LL, Blank MA, Johanns J, Guzzo C, Sands BE, Hanauer SB, Targan S, Rutgeerts P, Ghosh S, de Villiers WJ, Panaccione R, Greenberg G, Schreiber S, Lichtiger S, Feagan BG; CERTIFI Study Group. Ustekinumab induction and maintenance therapy in refractory Crohn's disease. N Engl J Med. 2012 Oct 18;367(16):1519-28. doi: 10.1056/NEJMoa1203572.

Reference Type: DERIVED

PMID: 23075178 (View on PubMed)

Other Identifiers

C0743T26

Identifier Type: OTHER

Identifier Source: secondary_id

CR015238

Identifier Type: -

Identifier Source: org_study_id