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

Centocor Ortho Biotech

Status and phase: Completed; Phase 2

Conditions: Crohn Disease

Treatments: Drug: Ustekinumab 4.5 mg/kg; Drug: Ustekinumab 90 mg; Drug: Placebo IV; Drug: Placebo SC

Study type: Interventional

Funder types: Industry

Identifiers

NCT00265122

C0379T07 (Other Identifier)

CR005287

Details and patient eligibility

About

The purpose of this study is to examine the safety and efficacy of CNTO 1275 in participants with active Crohn's Disease.

Full 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.

Enrollment: 131 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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131 participants in 6 patient groups

Population 1: Placebo SC followed by ustekinumab SC

Experimental group

Description:

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.

Treatment:

Drug: Placebo SC

Drug: Ustekinumab 90 mg

Population 1: Ustekinumab SC followed by Placebo SC:

Experimental group

Description:

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.

Treatment:

Drug: Placebo SC

Drug: Ustekinumab 90 mg

Population 1: Placebo IV followed by ustekinumab IV

Experimental group

Description:

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.

Treatment:

Drug: Placebo IV

Drug: Ustekinumab 4.5 mg/kg

Population 1: Ustekinumab IV followed by Placebo IV:

Experimental group

Description:

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.

Treatment:

Drug: Placebo IV

Drug: Ustekinumab 4.5 mg/kg

Population 2: Ustekinumab SC

Experimental group

Description:

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

Treatment:

Drug: Ustekinumab 90 mg

Population 2: Ustekinumab IV

Experimental group

Description:

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

Treatment:

Drug: Ustekinumab 4.5 mg/kg