A Study to Evaluate the Safety and Efficacy of Ustekinumab in Patients With Moderately to Severely Active Crohn's Disease Who Have Failed or Are Intolerant to Tumor Necrosis Factor (TNF) Antagonist Therapy (UNITI-1)

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 3

Conditions: Inflammatory Bowel Disease; Colitis; IBD; Crohn's Disease

Treatments: Drug: Group 2 ustekinumab 130 mg; Drug: Group 3: ustekinumab approximately 6 mg/kg; Drug: Group 1: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01369329

CR018415

2010-022758-18 (EudraCT Number)

CNTO1275CRD3001 (Other Identifier)

Details and patient eligibility

About

This study (UNITI-1) will compare the effects (both positive and negative) of an initial treatment with ustekinumab to placebo over 8 weeks, in patients with moderately to severely active Crohn's disease who have either failed or could not tolerate at least one TNF-antagonist medications in the past (specifically, infliximab, adalimumab, or certolizumab pegol).

Full description

This study (CNTO1275CRD3001 or "UNITI-1") 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 who previously did not respond to, lost response to, or could not tolerate TNF-antagonist medications (specifically, infliximab, adalimumab or certolizumab pegol). 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 703 patients. 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'' [NCT01369355]), 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 (either placebo or ustekinumab) at the first (week 0) visit when they enter the study.There are 3 treatment groups: 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).

Enrollment: 769 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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's Disease Activity Index (CDAI) score of >= 220 and <= 450
• Have received infliximab, adalimumab, or certolizumab pegol at a dose approved for the treatment of Crohn disease and did not respond initially (ie, primary nonresponse)
• Or responded initially but then lost response with continued therapy (ie, secondary nonresponse)
• Or were intolerant to the medication
• 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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769 participants in 3 patient groups, including a placebo group

001

Placebo Comparator group

Description:

Group 1: Placebo Form=solution for injection route=intravenous use in a single dose.

Treatment:

Drug: Group 1: Placebo

002

Experimental group

Description:

Group 2 ustekinumab 130 mg Type=exact unit=mg number=130 form=solution for injection route= intravenous use in a single dose.

Treatment:

Drug: Group 2 ustekinumab 130 mg

003

Experimental group

Description:

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).

Treatment:

Drug: Group 3: ustekinumab approximately 6 mg/kg