A Study of Mirikizumab (LY3074828) in Participants With Moderate to Severe Ulcerative Colitis

Lilly

Status and phase: Completed; Phase 2

Conditions: Ulcerative Colitis

Treatments: Drug: Placebo; Drug: Mirikizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02589665

2015-003123-57 (EudraCT Number)

15829

I6T-MC-AMAC (Other Identifier)

Details and patient eligibility

About

The main purpose of this study is to test the hypothesis that treatment with mirikizumab is superior to placebo in providing clinical benefit to participants with moderate to severe ulcerative colitis (UC). This study will also investigate how the body processes the drug.

Enrollment: 249 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have moderate to severe active UC as defined by a Mayo score of 6 to 12 with an endoscopic subscore ≥2 within 14 days before the first dose of study treatment (note: a partial Mayo score of at least 4 and other eligibility criteria must have been met before endoscopy is performed as a study procedure)
• Have evidence of UC extending proximal to the rectum (≥15 centimeters [cm] of involved colon)
• Up-to-date colorectal cancer surveillance (performed according to local standard), for subjects with family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor
• Participants must either: be naive to biologic therapy (eg, tumor necrosis factor [TNF] antagonists or vedolizumab) and have at least 1 of the following: inadequate response or failure to tolerate current treatment with oral or intravenous corticosteroids or immunomodulators (6-mercaptopurine or azathioprine) or history of corticosteroid dependence (an inability to successfully taper corticosteroids without return of UC) OR have received treatment with 1 or more biologic agents (eg, TNF antagonists or vedolizumab) at doses approved for the treatment of UC with documented history of failure to respond to or tolerate such treatment

Exclusion criteria

• Have been diagnosed with indeterminate colitis, proctitis (distal disease involving the rectum only; less than 15 cm from the anal verge) or Crohn's Disease
• Have had surgery for treatment of UC or are likely to require surgery for UC during the study
• Have received any of the following for treatment of UC: cyclosporine or thalidomide within 30 days of screening, corticosteroid enemas, corticosteroid suppositories, or topical treatment with 5-aminosalicyclic acid within 30 days of screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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249 participants in 10 patient groups, including a placebo group

50 mg Mirikizumab IV Q4W (Induction)

Experimental group

Description:

50 mg mirikizumab administered every 4 weeks (Q4W) intravenously (IV) during the induction period. Participants who do not have a clinical response may choose to participate in the unblinded study extension period.

Treatment:

Drug: Mirikizumab

200 mg Mirikizumab IV Q4W (induction)

Experimental group

Description:

200 mg mirikizumab administered every 4 weeks (Q4W) intravenously (IV) during the induction period. Participants who do not have a clinical response may choose to participate in the unblinded study extension period.

Treatment:

Drug: Mirikizumab

600 mg Mirikizumab IV Q4W (Induction)

Experimental group

Description:

600 mg mirikizumab administered every 4 weeks (Q4W) intravenously (IV) during the induction period. Participants who do not have a clinical response may choose to participate in the unblinded study extension period.

Treatment:

Drug: Mirikizumab

Placebo IV Q4W (Induction)

Placebo Comparator group

Description:

Placebo administered every 4 weeks (Q4W) intravenously (IV) during the induction period.

Treatment:

Drug: Placebo

200 mg Mirikizumab SC Q4W (Maintenance)

Experimental group

Description:

Induction mirikizumab responders were re-randomized: 200 mg mirikizumab administered subcutaneously (SC) Q4W during the maintenance period.

Treatment:

Drug: Mirikizumab

200 mg Mirikizumab SC Q12W (Maintenance)

Experimental group

Description:

Induction mirikizumab responders were re-randomized: 200 mg mirikizumab administered subcutaneously (SC) once every 12 weeks (Q12W) during the maintenance period.

Treatment:

Drug: Mirikizumab

Placebo SC Q4W (Maintenance)

Placebo Comparator group

Description:

Induction placebo responders: Placebo administered subcutaneously (SC) Q4W during the maintenance period.

Treatment:

Drug: Placebo

600mg Mirikizumab IV Q4W Extension Open-Label

Experimental group

Description:

Induction non-responders: 600 mg mirikizumab administered intravenously (IV) once every 4 weeks (Q4W) during the Extension Open-Label.

Treatment:

Drug: Mirikizumab

1000mg Mirikizumab IV Q4W Extension Open-Label

Experimental group

Description:

Induction non-responders: 1000 mg mirikizumab administered intravenously (IV) once every 4 weeks (Q4W) during the Extension Open-Label.

Treatment:

Drug: Mirikizumab

200mg Mirikizumab SC Q4W Extension Open-Label

Experimental group

Description:

Extension Induction responders: 200 mg mirikizumab administered subcutaneously (SC) once every 4 weeks (Q4W) during the Extension Open-Label

Treatment:

Drug: Mirikizumab