A Study to Evaluate the Safety and Efficacy of Itacitinib in Moderate to Severe Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of itacitinib in participants with moderate to severe ulcerative colitis (UC).

Official Title
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A Phase 2, Double-Blind, Dose-Ranging, Placebo-Controlled Study With Open-Label Extension to Evaluate the Safety and Efficacy of Itacitinib in Moderate to Severe Ulcerative Colitis

Conditions
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Moderate to Severe Ulcerative Colitis

Intervention / Treatment
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* Drug: Itacitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of UC at least 12 weeks before screening based on clinical, endoscopic, and histopathological evidence. Have a 3-component Mayo score of 4 to 9, which includes a modified Mayo Endoscopy Score (mMES) of ≥ 2 as determined by a central reader, a rectal bleeding score of ≥ 1, and a stool frequency score of ≥ 1. Must have failed or be intolerant to (discontinued the medication due to an adverse event as determined by the investigator) at least 1 of the following treatments for UC: Oral corticosteroids, azathioprine or 6-mercaptopurine, biologic therapy (eg, infliximab, vedolizumab or adalimumab). Participants currently receiving the following treatment(s) for UC are eligible, provided they have been receiving acceptable and stable dose(s): oral 5-ASA or oral corticosteroids. No evidence of active or latent or inadequately treated tuberculosis infection. Willingness to avoid pregnancy or fathering children. Exclusion Criteria: Clinical signs of fulminant colitis or toxic megacolon. Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical or radiographic findings suggestive of Crohn's disease. Disease limited to the distal 15 cm of the colon. Receiving (or expected to receive) the following therapies within protocol-designated timeframes before the baseline visit or during the study: Natalizumab; anti-TNF therapy; Vedolizumab or any investigational anti-adhesion molecule therapy; Ustekinumab or any on or off label biologic therapy; interferon therapy; cyclosporine, mycophenolate, or tacrolimus; daily dose of oral corticosteroids ≥ 25 mg prednisone or equivalent; intravenous corticosteroids; rectally administered formulation of corticosteroids or 5-aminosalicylic acid; and AZA, 6-MP, or methotrexate. Enema treatments within 2 weeks of the baseline visit, with the exception of enema bowel preparations for clinical assessments. Positive stool examinations for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile toxin at the screening visit. Other immunocompromised states and history of opportunistic infections. History of stomach or intestinal surgery, including bariatric surgery (Note: appendectomy and/or cholecystectomy, is allowed). o surgery for UC or likely to require surgery for UC during the study. If at risk for colorectal cancer, must have had a colonoscopy within protocol-defined timeframes. History of recurrent, disseminated, or multiple dermatomal herpes zoster. History of alcohol or drug abuse. History of active malignancy within 5 years of screening, excluding superficial basal and squamous cell carcinoma of the skin and adequately treated carcinoma in situ of the cervix. Current or recent history (within 30 days before randomization) of a clinically meaningful viral, bacterial, fungal, parasitic, or mycobacterial infection. Previously received either lymphocyte apheresis or selective monocyte granulocyte apheresis (eg, Cellsorba) within 1 year of baseline. History of unstable ischemic heart disease or uncontrolled hypertension. Positive serology test results for HIV, for hepatitis B surface antigen or core antibody, or for HCV antibody with detectable RNA at screening. Participants taking potent systemic CYP3A4 inhibitors or inducers or fluconazole within 2 weeks or 5 half-lives (whichever is longer) of baseline. Participants taking P-gp substrates with narrow therapeutic index, including digoxin within 2 weeks or 5 half-lives (whichever is longer) of baseline.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Itacitinib<br> | Drug: Itacitinib<br>* In the double-blind period, itacitinib administered orally once or twice daily at the protocol-defined dose according to treatment group randomization. In the open-label extension, itacitinib administered at doses determined from the double-blind period.<br>* Other names: INCB039110;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo administered orally twice daily in the double-blind period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with a Clinical Response | To evaluate the efficacy of itacitinib inducing a Clinical Response. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with Endoscopic Response | To evaluate the efficacy of itacitinib on endoscopic outcomes. | Week 8 | 
| Proportion of participants with Mucosal Healing | To evaluate the efficacy of itacitinib on endoscopic outcomes. | Week 8 | 
| Proportion of participants in Endoscopic Remission | To evaluate the efficacy of itacitinib on endoscopic outcomes. | Week 8 | 
| Proportion of participants in Clinical Remission | To evaluate the efficacy of itacitinib on clinical outcomes. | Week 8 | 
| Change from baseline in 3-component Mayo score | To evaluate the efficacy of itacitinib on clinical outcomes. | Week 8 | 
| Change from baseline in Physician's Global Assessment score | To evaluate the efficacy of itacitinib on clinical outcomes. | Week 8 | 
| Change in Quality of Life score as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) | To evaluate the efficacy of itacitinib on quality of life outcomes. | Week 8 | 
| Cmax of itacitinib | Maximum observed plasma concentrations. | Week 4 | 
| Ctau of itacitinib | Plasma concentrations | Weeks 2 and 4 | 
| Stool concentration of itacitinib - 30-hr collection |  | Week 4 | 
| Number of treatment-emergent adverse events | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug. | Up to approximately 60 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammatory bowel disease, ulcerative colitis, Janus kinase inhibitor, JAK1