A Study of the Safety and Efficacy of Ustekinumab (CNTO 1275) in Participants With Crohn's Disease

NCT ID: NCT00265122

Last Updated: 2014-02-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-04-30
• Study Completion Date: 2006-10-31

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.

Conditions

Crohn Disease

Study Design

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

Study Groups

Population 1: Placebo SC followed by ustekinumab SC

Placebo injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by ustekinumab 90 mg SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.

Group Type: EXPERIMENTAL

Ustekinumab 90 mg

Intervention Type: DRUG

one 90 mg SC injection each week for 4 weeks (Weeks 0-3 during Intervention Period 1 or Weeks 8-11 during Intervention Period 2 for Population 1 or Weeks 0-3 during Intervention Period 1 for Population 2)

Placebo SC

Intervention Type: DRUG

one SC injection each week for 4 weeks (Weeks 0-3 in Intervention Period 1 or Weeks 8-11 in Intervention Period 2 for Population 1 or at Weeks 0-3 in Intervention Period 1 for Population 2)

Population 1: Ustekinumab SC followed by Placebo SC:

Ustekinumab 90 mg injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by ustekinumab 90 mg SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.

Group Type: EXPERIMENTAL

Ustekinumab 90 mg

Intervention Type: DRUG

one 90 mg SC injection each week for 4 weeks (Weeks 0-3 during Intervention Period 1 or Weeks 8-11 during Intervention Period 2 for Population 1 or Weeks 0-3 during Intervention Period 1 for Population 2)

Placebo SC

Intervention Type: DRUG

one SC injection each week for 4 weeks (Weeks 0-3 in Intervention Period 1 or Weeks 8-11 in Intervention Period 2 for Population 1 or at Weeks 0-3 in Intervention Period 1 for Population 2)

Population 1: Placebo IV followed by ustekinumab IV

Placebo given as 1 intravenous (IV) infusion at Week 0 during Intervention Period 1 and ustekinumab 4.5 mg/kg given as one IV infusion at Week 8 during Intervention Period 2.

Group Type: EXPERIMENTAL

Ustekinumab 4.5 mg/kg

Intervention Type: DRUG

one IV infusion of 4.5 mg/kg over a period of not less than 2 hours at Week 0 in Intervention Period 1 or Week 8 in Intervention Period 2 for Population 1 or at Week 0 in Intervention Period 1 for Population 2

Placebo IV

Intervention Type: DRUG

one IV infusion over a period of not less than 2 hours at Week 0 in Intervention Period 1 for Population 1 and Population 2 or at Week 8 in Intervention Period 2 for Population 1

Population 1: Ustekinumab IV followed by Placebo IV:

Ustekinumab 4.5 mg/kg given as one intravenous(IV) infusion at Week 0 during Intervention Period 1 followed by placebo given as one IV infusion at Week 8 during Intervention Period 2.

Group Type: EXPERIMENTAL

Ustekinumab 4.5 mg/kg

Intervention Type: DRUG

one IV infusion of 4.5 mg/kg over a period of not less than 2 hours at Week 0 in Intervention Period 1 or Week 8 in Intervention Period 2 for Population 1 or at Week 0 in Intervention Period 1 for Population 2

Placebo IV

Intervention Type: DRUG

one IV infusion over a period of not less than 2 hours at Week 0 in Intervention Period 1 for Population 1 and Population 2 or at Week 8 in Intervention Period 2 for Population 1

Population 2: Ustekinumab SC

Ustekinumab 90 mg injected subcutaneously (SC) once a week at Weeks 0-3 during Intervention Period 1. No intervention given during Intervention Period 2.

Group Type: EXPERIMENTAL

Ustekinumab 90 mg

Intervention Type: DRUG

one 90 mg SC injection each week for 4 weeks (Weeks 0-3 during Intervention Period 1 or Weeks 8-11 during Intervention Period 2 for Population 1 or Weeks 0-3 during Intervention Period 1 for Population 2)

Population 2: Ustekinumab IV

Ustekinumab 4.5 mg given as one intravenous (IV) infusion at Week 0 during Intervention Period 1. No intervention given during Intervention Period 2.

Group Type: EXPERIMENTAL

Ustekinumab 4.5 mg/kg

Intervention Type: DRUG

one IV infusion of 4.5 mg/kg over a period of not less than 2 hours at Week 0 in Intervention Period 1 or Week 8 in Intervention Period 2 for Population 1 or at Week 0 in Intervention Period 1 for Population 2

Interventions

Ustekinumab 90 mg

one 90 mg SC injection each week for 4 weeks (Weeks 0-3 during Intervention Period 1 or Weeks 8-11 during Intervention Period 2 for Population 1 or Weeks 0-3 during Intervention Period 1 for Population 2)

Intervention Type: DRUG

Ustekinumab 4.5 mg/kg

one IV infusion of 4.5 mg/kg over a period of not less than 2 hours at Week 0 in Intervention Period 1 or Week 8 in Intervention Period 2 for Population 1 or at Week 0 in Intervention Period 1 for Population 2

Intervention Type: DRUG

Placebo SC

one SC injection each week for 4 weeks (Weeks 0-3 in Intervention Period 1 or Weeks 8-11 in Intervention Period 2 for Population 1 or at Weeks 0-3 in Intervention Period 1 for Population 2)

Intervention Type: DRUG

Placebo IV

one IV infusion over a period of not less than 2 hours at Week 0 in Intervention Period 1 for Population 1 and Population 2 or at Week 8 in Intervention Period 2 for Population 1

Intervention Type: DRUG

Other Intervention Names

CNTO 1275; CNTO 1275

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

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

Sponsors

Centocor, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Centocor Clinical Trial

Role: STUDY_DIRECTOR

Centocor, Inc.

Locations

Scottsdale, Arizona, United States

Anaheim, California, United States

Sacramento, California, United States

San Francisco, California, United States

Bristol, Connecticut, United States

New Haven, Connecticut, United States

Jacksonville, Florida, United States

Miami, Florida, United States

Indianapolis, Indiana, United States

Topeka, Kansas, United States

Lexington, Kentucky, United States

Louisville, Kentucky, United States

Baton Rouge, Louisiana, United States

Metairie, Louisiana, United States

New Orleans, Louisiana, United States

Laurel, Maryland, United States

Chesterfield, Michigan, United States

Troy, Michigan, United States

Rochester, Minnesota, United States

Omaha, Nebraska, United States

Great Neck, New York, United States

New York, New York, United States

Chapel Hill, North Carolina, United States

Charlotte, North Carolina, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Columbus, Ohio, United States

Oklahoma City, Oklahoma, United States

Portland, Oregon, United States

Beaver Falls, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Providence, Rhode Island, United States

Columbia, South Carolina, United States

Germantown, Tennessee, United States

Knoxville, Tennessee, United States

Memphis, Tennessee, United States

Nashville, Tennessee, United States

Austin, Texas, United States

Dallas, Texas, United States

Houston, Texas, United States

Ogden, Utah, United States

Salt Lake City, Utah, United States

Charlottesville, Virginia, United States

Christiansburg, Virginia, United States

Richmond, Virginia, United States

Everett, Washington, United States

Seattle, Washington, United States

Tacoma, Washington, United States

Madison, Wisconsin, United States

Milwaukee, Wisconsin, United States

Leuven, , Belgium

Edmonton, Alberta, Canada

Vancouver, British Columbia, Canada

Winnipeg, Manitoba, Canada

Toronto, Ontario, Canada

Hamilton, , Canada

London, , Canada

Countries

United States; Belgium; Canada

References

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)

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.

Reference Type: DERIVED

PMID: 18706417 (View on PubMed)

Other Identifiers

C0379T07

Identifier Type: OTHER

Identifier Source: secondary_id

CR005287

Identifier Type: -

Identifier Source: org_study_id