Identification of Biomarkers of Janus Kinase Inhibitor Therapy in Patients With Ulcerative Colitis

PhaRmacOkinetics and PHarmacodynamic BiomarkErs of Janus Kinase Inhibitor Therapy in PatIents With Ulcerative Colitis (PROPHETIC)

This study aims to provide new mechanistic insights into the molecular determinants of response or nonresponse to Janus Kinase inhibitor therapy and the biological heterogeneity that exists in Ulcerative Colitis. This study will include patients who are initiating Janus Kinase inhibitor therapy according to standard of care. This study consists of:

• Part 1: 8 or 10 week induction therapy followed by an 8-week maintenance therapy
• Part 2: Patients who continue Janus Kinas inhibitor therapy after part 1 will be followed further for a total of 2 years, or until discontinuation of Janus Kinase inhibitor therapy (whichever is first)

Inclusion Criteria:

1.18 years of age or older.

2.Male or nonpregnant, nonlactating females.

3.Diagnosis of Ulcerative Colitis for at least 3 months prior to screening.

4.Moderately to severely active Ulcerative Colitis (total Mayo Clinic Score ≥ 6), with objective evidence of inflammation defined by a Mayo endoscopic subscore (MES) ≥ 2 and disease extending > 15 cm from the anal verge.

5.Physician plans to administer Janus Kinase inhibitor for at least 8 weeks of induction therapy as part of Standard of Care (SOC).

6.Documentation of a negative test result for latent tuberculosis within the last 12 months, or according to routine clinical practice.

7.Able to participate fully in all aspects of this clinical trial, including collection of tissue biopsies.

8.Written informed consent must be obtained and documented.

Exclusion Criteria:

1. Diagnosis of Crohn's disease or indeterminate colitis.
2. An active, serious infection, including localized infections.
3. Concomitant administration of biological therapies for Ulcerative Colitis or potent immunosuppressants, such as azathioprine and cyclosporine. Subjects with previous exposure to these treatments should undergo an appropriate washout period according to local practice prior to starting Janus Kinase inhibitor, in keeping with routine clinical practice.
4. Hematology laboratory (e.g., absolute lymphocyte count, absolute neutrophil count, and hemoglobin that contraindicate the product label.
5. Interval between live vaccinations and initiation of tofacitinib therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.
6. Serious underlying disease other than Ulcerative Colitis that in the opinion of the investigator may interfere with the subject's ability to participate fully in the study.