Clinical trial NCT03627052: A Study to Evaluate the Safety and Efficacy of Itacitinib in Moderate to Severe Ulcerative Colitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Moderate to Severe Ulcerative Colitis
Keywords: Inflammatory bowel disease
ulcerative colitis
Janus kinase inhibitor
JAK1
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2018-08-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of participants with a Clinical Response
timeFrame: Week 8
Secondary outcomes:
measure: Proportion of participants with Endoscopic Response
timeFrame: Week 8
measure: Proportion of participants with Mucosal Healing
timeFrame: Week 8
measure: Proportion of participants in Endoscopic Remission
timeFrame: Week 8
measure: Proportion of participants in Clinical Remission
timeFrame: Week 8
measure: Change from baseline in 3-component Mayo score
timeFrame: Week 8
measure: Change from baseline in Physician's Global Assessment score
timeFrame: Week 8
measure: Change in Quality of Life score as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ)
timeFrame: Week 8
measure: Cmax of itacitinib
timeFrame: Week 4
measure: Ctau of itacitinib
timeFrame: Weeks 2 and 4
measure: Stool concentration of itacitinib -~30-hr collection
timeFrame: Week 4
measure: Number of treatment-emergent adverse events
timeFrame: Up to approximately 60 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Incyte Corporation
name: Kurt Brown, MD
role: STUDY_DIRECTOR
References: