Clinical trial NCT00771667: 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
Official title: A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Ustekinumab Therapy in Subjects With Moderately to Severely Active Crohn's Disease Previously Treated With TNF Antagonist Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: Interleukin-12
Inflammation
Research study
Ustekinumab
CNTO1275
Interleukin-23
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
First posted: 2008-10-13
Enrollment: 526
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: 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.

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.

Primary outcomes:
measure: Number of Participants With Clinical Response at Week 6
timeFrame: Baseline to Week 6
Secondary outcomes:
measure: Number of Participants With Clinical Remission at Week 6
timeFrame: Baseline to Week 6
measure: Number of Participants With Clinical Response at Week 4
timeFrame: Baseline to Week 4
measure: Number of Participants With Clinical Response at Week 8
timeFrame: Baseline to Week 8
measure: Number of Participants With Clinical Remission at Week 8
timeFrame: Baseline to Week 8
measure: Number of Participants With Clinical Remission at Week 22 (Among Responders From Week 6)
timeFrame: Baseline to Week 22
measure: Number of Participants With Clinical Response at Week 22 (Among Responders From Week 6)
timeFrame: Baseline to Week 22
Other outcomes:
Locations:
city: Mobile
country: United States
state: Alabama
city: Scottsdale
country: United States
state: Arizona
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Roseville
country: United States
state: California
city: San Carlos
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Englewood
country: United States
state: Colorado
city: Lakewood
country: United States
state: Colorado
city: Littleton
country: United States
state: Colorado
city: Hamden
country: United States
state: Connecticut
city: Gainesville
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Jacksonville
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state: Florida
city: Miami
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city: Naples
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city: Panama City
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city: Pembroke Pines
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state: Florida
city: Port Charlotte
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state: Florida
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state: Florida
city: South Miami
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city: Tampa
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state: Florida
city: Vero Beach
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state: Florida
city: Winter Park
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state: Florida
city: Zephyrhills
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state: Florida
city: Atlanta
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state: Georgia
city: Columbus
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state: Georgia
city: Decatur
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state: Georgia
city: Macon
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state: Georgia
city: Newnan
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state: Georgia
city: Arlington Heights
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state: Illinois
city: Chicago
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city: Evanston
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city: Indianapolis
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city: Clive
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state: Iowa
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state: Kentucky
city: Louisville
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city: Baltimore
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state: Maryland
city: Chevy Chase
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state: Massachusetts
city: Burlington
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city: Worcester
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state: Minnesota
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state: Mississippi
city: Mexico
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state: New Hampshire
city: Egg Harbor
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state: New Jersey
city: Great Neck
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city: Ny
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city: Poughkeepsie
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city: Setauket
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city: Stony Brook
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city: Chapel Hill
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state: North Carolina
city: Charlotte
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city: East Melbourne
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city: Fitzroy
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city: Frankston
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city: Fremantle
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city: Garran
country: Australia
city: Herston
country: Australia
city: Parkville
country: Australia
city: Prahran
country: Australia
city: South Brisbane
country: Australia
city: Innsbruck
country: Austria
city: Linz N/A
country: Austria
city: Salzburg
country: Austria
city: Wien
country: Austria
city: Bonheiden
country: Belgium
city: Brussel
country: Belgium
city: Bruxelles
country: Belgium
city: Edegem
country: Belgium
city: Kortrijk
country: Belgium
city: Liege
country: Belgium
city: Louvain
country: Belgium
city: Roeselare
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: Hamilton
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Saskatoon
country: Canada
state: Saskatchewan
city: Quebec
country: Canada
city: Amiens Cedex 1 80
country: France
city: Grenoble
country: France
city: Lille
country: France
city: Nice
country: France
city: Paris Cedex 10
country: France
city: Paris
country: France
city: Pessac
country: France
city: Rouen Cedex
country: France
city: Toulouse Cedex 9 N/A
country: France
city: Berlin N/A
country: Germany
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Kiel
country: Germany
city: Leipzig
country: Germany
city: Lÿneburg
country: Germany
city: Markkleeberg
country: Germany
city: Minden
country: Germany
city: München
country: Germany
city: Münster
country: Germany
city: Regensburg
country: Germany
city: Afula
country: Israel
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Kfar-Saba
country: Israel
city: Petah-Tikva
country: Israel
city: Tel Aviv
country: Israel
city: Amersfoort
country: Netherlands
city: Amsterdam
country: Netherlands
city: Leiden
country: Netherlands
city: Maastricht
country: Netherlands
city: Rotterdam
country: Netherlands
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Barcelona
country: Spain
city: Cordoba
country: Spain
city: Leon N/A
country: Spain
city: Madrid
country: Spain
city: Oviedo
country: Spain
city: Palma De Mallorca N/A
country: Spain
city: Sabadell
country: Spain
city: Zaragoza
country: Spain
city: Bristol
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Coventry
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Harrow
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Norwich
country: United Kingdom
city: Nottinghamshirecc
country: United Kingdom
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. 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: 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: 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.
citation: 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.