A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (UNIFI)

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 3

Conditions: Colitis, Ulcerative; Inflammatory Bowel Diseases

Treatments: Drug: Ustekinumab IV; Drug: Placebo IV; Drug: Ustekinumab SC; Drug: Placebo SC

Study type: Interventional

Funder types: Industry

Identifiers

NCT02407236

CR106920

CNTO1275UCO3001 (Other Identifier)

2014-005606-38 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of ustekinumab as intravenous (IV: into the vein) infusion in induction study in participants with moderately to severely active Ulcerative Colitis (UC) and as subcutaneous (SC) administration in maintenance study in participants with moderately to severely active Ulcerative Colitis (UC) who have demonstrated a clinical response to Induction treatment with IV ustekinumab.

Full description

This is a Phase 3, randomized (assignment of study drug by chance), double-blind (neither the participant or study staff will know the identity of study drugs), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (a medical research study comparing the response in 2 or more groups of participants receiving different interventions), multi-center (more than one clinical site will work on a medical research study), protocol of ustekinumab. The protocol will consist of 2 studies: an Induction study and a Maintenance study with unique endpoints. Screening period will be up to 8 Weeks. Induction study will be at least 8 weeks duration for each participant. Participant with clinical response in the Induction study will be eligible for the Maintenance study. The Maintenance study will be 44 weeks duration. After completion of the maintenance study, a long term extension will follow eligible participants for an additional 3 years. Clinical remission will be evaluated at Week 8 in the Induction study. Clinical remission among ustekinumab Induction responders will be evaluated at week 44 in the Maintenance study. Participants' safety will be monitored throughout.

Enrollment: 961 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has a clinical diagnosis of Ulcerative Colitis (UC) at least 3 months before Screening
• Has moderately to severely active UC, defined as a Baseline (Week 0) Mayo score of 6 to 12, including a Screening endoscopy subscore of the Mayo score greater than or equal to (>=) 2 as determined by a central reading of the video endoscopy
• Have failed biologic therapy, that is, have received treatment with 1 or more tumour necrosis factor (TNF) antagonists or vedolizumab at a dose approved for the treatment of UC, and have a documented history of failure to respond to or tolerate such treatment; OR Be naïve to biologic therapy (TNF antagonists or vedolizumab) or have received biologic therapy but have not demonstrated a history of failure to respond to, or tolerate, a biologic therapy and have a prior or current UC medication history that includes at least 1 of the following: a. Inadequate response to or failure to tolerate current treatment with oral corticosteroids or immunomodulators (6-mercaptopurine [6-MP] or azathioprine [AZA]) OR b. History of failure to respond to, or tolerate, at least 1 of the following therapies: oral or IV corticosteroids or immunomodulators (6-MP or AZA) OR c. History of corticosteroid dependence (that is, an inability to successfully taper corticosteroids without a return of the symptoms of UC)
• Before the first administration of study agent, the following conditions must be met: vedolizumab must have been discontinued for at least 4 months and anti-tumor necrosis factors (TNFs) for at least 8 weeks

Exclusion criteria

• Has severe extensive colitis and is at imminent risk of colectomy
• Has UC limited to the rectum only or to < 20 centimeters (cm) of the colon
• Presence of a stoma or history of a fistula
• Participants with history of extensive colonic resection (for example, less than 30 cm of colon remaining) that would prevent adequate evaluation of the effect of study agent on clinical disease activity
• Participants with history of colonic mucosal dysplasia. Participants will not be excluded from the study because of a pathology finding of "indefinite dysplasia with reactive atypia''

Trial design

961 participants in 10 patient groups, including a placebo group

Induction Study - Placebo Intravenous (IV)

Placebo Comparator group

Description:

Participants will be randomized to receive single dose of placebo as Intravenous (IV: into the vein) infusion at Week 0. Participants with clinical response at Week 8 will be eligible to enter the Maintenance study, but will not be randomized.

Treatment:

Drug: Placebo IV

Induction Study - Ustekinumab 130 milligram (mg) IV

Experimental group

Description:

Participants will be randomized to receive single dose of ustekinumab 130 mg as IV infusion at Week 0. Participants with clinical response at Week 8 will be eligible to enter the Maintenance study and will be randomized.

Treatment:

Drug: Ustekinumab IV

Induction Study - Ustekinumab 6 mg/kg IV

Experimental group

Description:

Participants will be randomized to receive ustekinumab approximating 6 mg/kg of body weight, as intravenous infusion at Week 0. Participants with clinical response at Week 8 will be eligible to enter the Maintenance study and will be randomized.

Treatment:

Drug: Ustekinumab IV

Induction Study- Placebo- Nonresponsders at Week 8

Other group

Description:

Participants without clinical response to placebo at Week 8 will receive a single IV infusion of ustekinumab approximating 6mg/kg along with matching subcutaneous (SC) placebo (to maintain the blind). Participants in clinical response at Week 16 will be eligible to enter Maintenance study and will be randomized.

Treatment:

Drug: Placebo SC

Drug: Ustekinumab IV

Induction study-Ustekinumab Nonresponders at Week 8

Other group

Description:

Participants without clinical response to ustekinumab (130 mg or 6 mg/kg \[IV\]) at Week 8 will receive a single dose of ustekinumab 90 mg subcutaneously along with matching placebo intravenously (to maintain the blind). Participants in clinical response at Week 16 (that is, delayed responders) will be eligible to enter Maintenance study, but will not be randomized.

Treatment:

Drug: Ustekinumab SC

Drug: Placebo IV

Maintenance Study - Placebo Subcutaneous (SC)

Placebo Comparator group

Description:

Participants in clinical response (at Week 8 or Week 16) to Induction treatment with single IV infusion of Ustekinumab will be randomized to receive placebo subcutaneously, beginning Week 0 of Maintenance study through Week 44.

Treatment:

Drug: Placebo SC

Maintenance Study - Ustekinumab 90mg SC every 12 weeks

Experimental group

Description:

Participants in clinical response (at Week 8 or Week 16) to Induction treatment with single IV infusion of Ustekinumab will be randomized to receive ustekinumab 90 mg subcutaneously every 12 weeks, beginning Week 0 of Maintenance study through Week 44.

Treatment:

Drug: Ustekinumab SC

Maintenance Study - Ustekinumab 90mg SC every 8 weeks (q8w)

Experimental group

Description:

Participants in clinical response (at Week 8 or Week 16) to Induction treatment with single IV infusion of Ustekinumab will be randomized to receive ustekinumab 90 mg subcutaneously every 8 weeks, beginning Week 0 of Maintenance study through Week 44.

Treatment:

Drug: Ustekinumab SC

Maintenance Study - Placebo IV - Responder - Placebo SC

Other group

Description:

Participants in clinical response to Induction treatment with IV Placebo will receive placebo subcutaneously, beginning Week 0 of Maintenance study through Week 44. Participants are not randomized.

Treatment:

Drug: Placebo SC

Maintenance Study-Delayed Responder-Ustekinumab 90mg SC q8w

Other group

Description:

Participants without clinical response to induction treatment ustekinumab (130 mg or 6 mg/kg \[IV\]) at Week 8 but in clinical response at Week 16 after receiving Induction Ustekinumab at week 8 (delayed responders) will receive ustekinumab 90 mg subcutaneously every 8 weeks, beginning Week 0 of Maintenance study through Week 44. Participants are not randomized.

Treatment:

Drug: Ustekinumab SC