Clinical trial NCT00265122: A Study of the Safety and Efficacy of Ustekinumab (CNTO 1275) in Participants With Crohn's Disease
Official title: A Multicenter, Randomized, Phase 2a Study of Human Monoclonal Antibody to IL-12p40 (CNTO 1275) in Subjects With Moderately to Severely Active Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn Disease
Keywords: Crohn Disease
Biologic
Infusion
Injection
CNTO 1275
Ustekinumab
C01275
IL-12p40
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
First posted: 2005-12-14
Enrollment: 131
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: The purpose of this study is to examine the safety and efficacy of CNTO 1275 in participants with active Crohn's Disease.

Detailed description: This is a multicenter, randomized study of IL-12p40 (CNTO 1275), hereafter referred to as ustekinumab, in 2 populations of participants with moderately to severely active Crohn's disease of at least 6 weeks duration. A total of approximately 120 volunteers will participate in this study in Canada, Belgium, and the United States. Two separate groups of participants (Population 1 and Population 2) will be evaluated. The primary population of participants (Population 1) will consist of approximately 100 participants with Crohn's disease despite treatment with standard Crohn's disease medications (includes agents to decrease intestinal inflammation such as 5-ASA medications such as PENTASA, ASACOL), corticosteroids such as prednisone and/or other drugs known to suppress the immune system called immunomodulators such as azathioprine, 6-mercaptopurine, methotrexate, infliximab or adalimumab \[marketed under the trade name of HUMMIRA\]). Participants in Population 1 will be randomly assigned (assigned by chance, like "flipping a coin") to double-blind treatment (participants and study staff will not know the identity of the treatments) with ustekinumab and placebo (inactive substance) in 1 of 4 treatment groups as follows: (1) 4 weeks of treatment with ustekinumab 90 mg followed by 4 weeks of treatment with placebo injected subcutaneously (SC, under the skin), (II) 4 weeks of placebo followed by 4 weeks of ustekinumab 90 mg injected SC, (III) 1 intravenous (IV, in the vein) infusion of ustekinumab 4.5 mg/kg followed by 1 IV infusion of placebo, and (IV) 1 IV infusion of placebo followed by 1 IV infusion of ustekinumab 4.5 mg/kg. Population 2 consists of approximately 20 participants who failed to respond to previous therapy with infliximab (trade name REMICADE), a type of antibody that decreases inflammation in patients with moderate to severe Crohn's disease). All participants in Population 2 will receive open-label (un-blinded) treatment with ustekinumab 4.5 mg/kg administered SC for 4 weeks or as one IV infusion. Placebo will not be given to participants in Population 2. The duration of the study for each participant is 28 weeks (not including a screening period of up to 2 weeks) with participants returning at Week 54 to have blood samples collected to assess the concentration of ustekinumab and antibodies to ustekinumab. Adverse events (side-effects) as a measure of safety and tolerability and results from routine laboratory tests will be monitored and reported throughout the study from the time that informed consent is documented up to 3 days after the final blood sample collection at Week 54. Note: doses of ustekinumab used in the study were adjusted by a factor of 0.9 to be consistent with the corrected absorptivity constant for ustekinumab. Therefore, ustekinumab doses of 100 mg and 5 mg/kg previously stated in the study protocol have been restated as 90 mg and 4.5 mg/kg, respectively. No change was made to the amount of ustekinumab given to participants in this study.

Eligibility criteria: Inclusion Criteria:

* Have moderately to severly active Crohn's disease or fistulizing Crohn's disease for at least 6 weeks' duration with a Crohn's disease activity index (CDAI) score of \>=220 and \<=450
* In Population 1, participants must have had active disease despite treatment with 5-ASA compounds, antibiotics, corticosteroids, and/or immunomodulators, including anti-TNF agents. In Population 2, participants must have had active disease and have failed to respond to infliximab at the maximum approved dose and treatment regimen for Crohn's disease as defined in the US package insert.

Exclusion Criteria:

* Have local manifestations of Crohn's disease such as strictures, abscesses, or other disease complications for which surgery might be indicated
* Had intra-abdominal surgery within 6 months prior to entering the study
* Have received treatment with parenteral nutrition (ie, introduction of nutrition into the body via a route other than the mouth) (total parenteral nutrition \[TPN\]) within 6 weeks of baseline

Primary outcomes:
measure: Number of Participants in Population 1 With a Clinical Response at Week 8
timeFrame: Week 8
Secondary outcomes:
measure: Number of Participants in Population 2 With a Clinical Response at Week 8
timeFrame: Week 8
measure: Number of Participants in Population 1 With Clinical Remission at Week 8
timeFrame: Week 8
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: Anaheim
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Bristol
country: United States
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Indianapolis
country: United States
state: Indiana
city: Topeka
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Baton Rouge
country: United States
state: Louisiana
city: Metairie
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Laurel
country: United States
state: Maryland
city: Chesterfield
country: United States
state: Michigan
city: Troy
country: United States
state: Michigan
city: Rochester
country: United States
state: Minnesota
city: Omaha
country: United States
state: Nebraska
city: Great Neck
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Beaver Falls
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: Columbia
country: United States
state: South Carolina
city: Germantown
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Memphis
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Ogden
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Charlottesville
country: United States
state: Virginia
city: Christiansburg
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Everett
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Leuven
country: Belgium
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Toronto
country: Canada
state: Ontario
city: Hamilton
country: Canada
city: London
country: Canada
Study officials:
affiliation: Centocor, Inc.
name: Centocor Clinical Trial
role: STUDY_DIRECTOR
References:
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: Sandborn WJ, Feagan BG, Fedorak RN, Scherl E, Fleisher MR, Katz S, Johanns J, Blank M, Rutgeerts P; Ustekinumab Crohn's Disease Study Group. A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease. Gastroenterology. 2008 Oct;135(4):1130-41. doi: 10.1053/j.gastro.2008.07.014. Epub 2008 Jul 17.