A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Patients With Moderately to Severely Active Crohn's Disease (UNITI-2)

Study Overview
=================
Brief Summary
-----------------
This study (UNITI-2) will compare the effects (both positive and negative) of an initial treatment with ustekinumab to a placebo over 8 weeks in patients with moderately to severely active Crohn's disease.

Detailed Description
-----------------
This study (CNTO1275CRD3002 or UNITI-2) examines ustekinumab (an antibody medication that inhibits the inflammatory proteins IL-12 and IL-23) versus a placebo (otherwise identical except without the ustekinumab antibody) given intravenously (by an IV) in adults with moderately to severely active Crohn's disease. Ustekinumab (also known as Stelara) is approved as a treatment for the skin condition of moderate to severe plaque-type psoriasis, but this study will examine if ustekinumab can provide benefit in Crohn's disease and also assess for any risks or side effects. Both the positive and negative outcomes of IV placebo versus two different doses of IV ustekinumab will be tracked and compared over eight weeks, in approximately 612 patients who have previously failed or were intolerant to corticosteroids or immunomodulators (methotrexate, azathioprine, or 6-mercaptopurine) or are dependent on corticosteroid medications. Patients enrolling in this study will be assigned to one of the 3 treatment groups by chance (randomly, like rolling dice), and all will receive a single IV administration of study agent at the first study visit (after the screening period), and then will be asked to return for 3 additional visits through Week 8. Patients who complete this study through the Week 8 visit and remain eligible can enter the maintenance study (CNTO1275CRD3003 or IM-UNITI), where they will receive additional study agent, including the administration of ustekinumab in patients who receive placebo in this study and have not had improvement in their Crohn's disease. Patients who do not enter the CNTO1275CRD3003 study will have a final safety follow-up visit approximately 20 weeks after they received study agent when they entered into this study at the Week 0 visit. .All patients will receive a single intravenous (IV) administration of study drug (placebo or ustekinumab) at the start of the study.There are 3 treatment groups in this study: Group 1: Placebo; Group 2: ustekinumab 130 mg, Group 3: weight-range based ustekinumab doses approximating ustekinumab 6 mg/kg: 260 mg (weight <= 55 kg), 390 mg (weight > 55 kg and <= 85 kg), and 520 mg (weight > 85 kg).

Official Title
-----------------
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Subjects With Moderately to Severely Active Crohn's Disease (UNITI-2)

Conditions
-----------------
IBD, Crohn's Disease, Inflammatory Bowel Disease, Colitis

Intervention / Treatment
-----------------
* Drug: Group 1: Placebo
* Drug: Group 2 ustekinumab 130 mg
* Drug: Group 3: ustekinumab approximately 6 mg/kg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have Crohn's disease of at least 3 months' duration with colitis, ileitis, or ileocolitis, confirmed at some time in the past by radiography, histology, or endoscopy Have active Crohn's disease, defined as a baseline Crohn Disease Activity Index (CDAI) score of >= 220 and <= 450, with confirmation of active inflammation Has failed conventional therapy as demonstrated by having received corticosteroids and/or immunomodulators(ie, AZA, MTX, or 6-MP) at adequate therapeutic doses OR Have a history of failure to respond to or tolerate an adequate course of corticosteroids and/or immunomodulators (ie, AZA, MTX, or 6-MP) at adequate therapeutic doses OR Is corticosteroid dependent or has had a history of corticosteroid dependency AND Has not previously demonstrated failure of or intolerance to 1 or more TNF-antagonist therapies (ie, infliximab, adalimumab, or certolizumab pegol) per study criteria Have screening laboratory test results within protocol-specified parameters Exclusion Criteria: Patients who have had any kind of bowel resection within 6 months Are pregnant or planning pregnancy (both men and women) while enrolled in the study or for 20 weeks after receiving study agent Patients who have received infliximab, adalimumab or certolizumab pegol < = 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 Patients who have previously received a biologic agent targeting IL-12 or IL-23, including but not limited to ustekinumab (CNTO 1275) or briakinumab (ABT-874)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo IV<br>Group 1: Placebo Form=solution for injection route=intravenous use in a single dose. | Drug: Group 1: Placebo<br>* Form=solution for injection, route=intravenous use, in a single dose.<br>|
| Experimental: Ustekinumab 130 milligram (mg)<br>Group 2 ustekinumab 130 mg Type=exact unit=mg number=130 form=solution for injection route= intravenous use in a single dose. | Drug: Group 2 ustekinumab 130 mg<br>* Type=exact, unit=mg, number=130, form=solution for injection, route= intravenous use, in a single dose.<br>|
| Experimental: Ustekinumab approximately ( ) 6 milligram per kilogram (mg/kg)<br>Group 3: ustekinumab approximately 6 mg/kg Type=range unit=mg/kg number=6 form=solution for injection route= intravenous use in a single dose.weight-range based ustekinumab doses approximating ustekinumab 6 mg/kg: 260 mg (weight <= 55 kg) 390 mg (weight > 55 kg and <= 85 kg) and 520 mg (weight > 85 kg). | Drug: Group 3: ustekinumab approximately 6 mg/kg<br>* Type=range, unit=mg/kg, number=6, form=solution for injection, route= intravenous use, in a single dose.weight-range based ustekinumab doses approximating ustekinumab 6 mg/kg: 260 mg (weight <= 55 kg), 390 mg (weight > 55 kg and <= 85 kg), and 520 mg (weight > 85 kg).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Response at Week 6 | Clinical response at Week 6 was defined as a reduction from baseline in the Crohn's Disease Activity Index (CDAI) score of greater than or equal (>=) 100 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). Participants with a baseline CDAI score of > = 220 to less than or equal (< =) 248 were considered to be in clinical response if a CDAI score of less than (<) 150 was attained. A decrease in CDAI score over time indicates improvement in disease activity. | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants in Clinical Remission at Week 8 | Clinical remission at Week 8 was defined as a Crohn's Disease Activity Index (CDAI) score of <150 points. | Week 8 | 
| Number of Participants in Clinical Response at Week 8 | Clinical response at Week 8 was defined as a reduction from baseline in the CDAI score of greater than or equal (>=) 100 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). Participants with a baseline CDAI score of > = 220 to less than or equal (< =) 248 were considered to be in clinical response if a CDAI score of less than (<) 150 was attained. A decrease in CDAI score over time indicates improvement in disease activity. | Week 8 | 
| Number of Participants With Crohn's Disease Activity Index (CDAI) 70 Point Response at Week 6 | 70-point response is defined as at least 70 points reduction in CDAI score (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 6 | 
| Number of Participants With CDAI 70 Point Response at Week 3 | 70-point response is defined as at least 70 points reduction in CDAI score (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity. | Week 3 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ustekinumab, moderately to severely active Crohn's Disease, Stelara, IBD, colitis, crohn, UNITI, Crohn's