A Study to Evaluate the Safety and Efficacy of Itacitinib in Moderate to Severe Ulcerative Colitis
- Conditions
- Moderate to Severe Ulcerative Colitis
- Interventions
- Drug: Placebo
- Registration Number
- NCT03627052
- Lead Sponsor
- Incyte Corporation
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of itacitinib in participants with moderate to severe ulcerative colitis (UC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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.
-
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - Itacitinib Itacitinib -
- Primary Outcome Measures
Name Time Method Proportion of participants with a Clinical Response Week 8 To evaluate the efficacy of itacitinib inducing a Clinical Response.
- Secondary Outcome Measures
Name Time Method Stool concentration of itacitinib -~30-hr collection Week 4 Proportion of participants with Mucosal Healing Week 8 To evaluate the efficacy of itacitinib on endoscopic outcomes.
Proportion of participants in Endoscopic Remission Week 8 To evaluate the efficacy of itacitinib on endoscopic outcomes.
Change from baseline in 3-component Mayo score Week 8 To evaluate the efficacy of itacitinib on clinical outcomes.
Cmax of itacitinib Week 4 Maximum observed plasma concentrations.
Proportion of participants with Endoscopic Response Week 8 To evaluate the efficacy of itacitinib on endoscopic outcomes.
Change from baseline in Physician's Global Assessment score Week 8 To evaluate the efficacy of itacitinib on clinical outcomes.
Change in Quality of Life score as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) Week 8 To evaluate the efficacy of itacitinib on quality of life outcomes.
Number of treatment-emergent adverse events Up to approximately 60 weeks Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.
Ctau of itacitinib Weeks 2 and 4 Plasma concentrations
Proportion of participants in Clinical Remission Week 8 To evaluate the efficacy of itacitinib on clinical outcomes.