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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Moderate to Severe Ulcerative Colitis
• Intervention / Treatment: Drug: Itacitinib; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo administered orally twice daily in the double-blind period.
Experimental: Itacitinib	Drug: Itacitinib; 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.; Other Names: INCB039110

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Kurt Brown, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2018
• Primary Completion (Actual): November 13, 2019
• Study Completion (Actual): November 13, 2019

Study Registration Dates

• First Submitted: August 8, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (Actual): August 13, 2018

Study Record Updates

• Last Update Posted (Actual): December 6, 2019
• Last Update Submitted That Met QC Criteria: December 4, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: ulcerative colitis; Inflammatory bowel disease; Janus kinase inhibitor; JAK1
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: INCB 39110-210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No