Inclusion Criteria for Part 1. 1. Male or female subjects must be at least at ≥18 and ≤75 years of age. 2. Subject has at least a three-month history of Ulcerative Colitis diagnosis at
3. Subject has active Ulcerative Colitis with a 9-point modified Mayo score of ≥ 5 at
baseline, with an endoscopic subscore of ≥ 2. 4. Subject is deemed by the physician as having inadequate response, loss of response or
intolerance to at least one conventional treatment (oral 5-ASA, immunosuppressants or
corticosteroids), or was previously exposed to anti-TNF therapy (e.g., infliximab,
adalimumab) or other biological treatment (e.g., vedolizumab) having. Discontinued the treatment for:
- - Infliximab: a minimum of 8 weeks prior to baseline.
- - Adalimumab: a minimum of 10 weeks prior to baseline.
- - Ustekinumab: a minimum of 14 weeks prior to baseline.
- - Vedolizumab: a minimum of 17 weeks prior to baseline.
Inclusion Criteria for Part 2 1. Subject has completed Part 1 and achieved clinical
response at week 8. Inclusion Criteria for Part 3. 1. Subject has completed the 8-week Part 1 and was classified as not meeting clinical
response criteria. OR Subject has discontinued treatment early in the Maintenance phase due
to disease worsening OR Subject has completed the Maintenance phase.
Study Exclusion Criteria for Part 1.
1. Subject has a diagnosis of indeterminate colitis, or clinical findings suggestive of
2. Subject with Ulcerative Colitis, which is confined to a proctitis (distal 15 cm or
3. Treatment naïve subject diagnosed with Ulcerative Colitis (without previous exposure
to any of the following therapies for UC treatment: oral 5-ASA, corticosteroids,
immunosuppressants, or biological treatments).
4. Subject is displaying clinical signs of ischemic colitis, fulminant colitis or toxic
5. Subject had previous surgery as a treatment for Ulcerative Colitis or likely to
require surgery during the study period.
6. Subject has evidence of pathogenic bowel infection. Subjects had Clostridium difficile
or other intestinal infection within 30 days of screening endoscopy or test positive
at screening for C.difficile toxin or other intestinal pathogens.
7. Subject currently has or has a history of active tuberculosis (TB) or latent TB
8. Subject is receiving any of the following therapies:
- - Azathioprine/6-mercaptopurine, methotrexate, thalidomide within 7 days prior to
- - Cyclosporine, mycophenolate, tacrolimus within 4 weeks prior to baseline.
- - Interferon therapy within 8 weeks prior to baseline.
- - Intravenous corticosteroids or rectally administered formulation of
corticosteroids or 5- ASA within 2 weeks prior to baseline.
9. Subject had any prior treatment with lymphocyte-depleting agents/therapies (such as
CamPath® [alemtuzumab], alkylating agents [e.g., cyclophosphamide or chlorambucil],
total lymphoid irradiation, etc.). Subjects who have received rituximab or other
selective B lymphocyte depleting agents are eligible if they have not received such
therapy for at least 1 year prior to baseline.
10. Subject has previously received JAK inhibitors, such as tofacitinib, baricitinib,
11. Subject with evidence of clinically relevant laboratory abnormalities which may affect
subject safety or interpretation of study results at screening. 12. Subject has a screening 12-lead ECG that demonstrates clinically relevant
abnormalities. 13. Subject currently has or had:
- - A clinically significant infection within 1 month of baseline (e.g., those
requiring hospitalization or parenteral antimicrobial therapy or have
- - A history of more than one episode of herpes zoster, or disseminated zoster
- - Any infection otherwise judged by the investigator to have the potential for
exacerbation by participation in the study.
- - Any infection requiring antimicrobial therapy within 2 weeks of screening.
14. Subject has current immunization with any live virus vaccine or history of
immunization with any live virus vaccine within 8 weeks of baseline.
15. Subject with a first-degree relative with a hereditary immunodeficiency.
16. Subject with a history of any lymphoproliferative disorder (such as EBV-related
lymphoproliferative disorder, as reported in some subjects on other immunosuppressive
drugs), history of lymphoma, leukemia, multiple myeloma, or signs and symptoms that
are suggestive of current lymphatic disease.
17. Subject has any condition possibly affecting oral drug absorption e.g., gastrectomy,
or clinically significant diabetic gastroenteropathy, or certain types of bariatric
surgery such as gastric bypass. (Procedures such as gastric banding, gastric balloon
that simply divide stomach into separate chambers, are NOT exclusionary.) Subject has
undergone significant trauma or major surgery within 4 weeks of baseline.
18. Women who are pregnant or lactating, or planning pregnancy while enrolled in the
study. Male who plan to donate sperm during the study and within 30 days after the
last dose of study drug.
19. Subject who has a history of alcohol or drug abuse with less than 6 months of
abstinence prior to baseline that in the opinion of the investigator will preclude
participation in the study.
20. Subject with malignancies or with a history of malignancies with exception of
adequately treated or excised non-metastatic basal cell or squamous cell cancer of the
21. Subject infected with human immunodeficiency virus (HIV) or hepatitis B or C viruses.
22. Subject has received any investigational drug or device within 3 months, or 5
half-lives (if known) prior to baseline.
23. Subject is receiving or expected to receive prohibited concomitant medication(s) in
the 4 weeks prior to the first dose of study drug and through follow-up visit.
24. Any other condition which in the opinion of the investigator would make the subject
unsuitable for inclusion in the study.
25. Subject with historical or current evidence of clinically significant cardiovascular,
neurological, psychiatric, renal, hepatic, immunological, gastrointestinal,
urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including
uncontrolled diabetes or thyroid disease), or hematological abnormalities that are
uncontrolled. Significant is defined as any disease that, in the opinion of the
Investigator, would put the safety of the subject at risk through participation, or
which would affect the efficacy or safety analysis if the disease/condition
exacerbated during the study.
26. Subject with a history of thromboembolic events, including deep vein thromboses (DVT),
pulmonary embolism (PE), and those with known inherited conditions that predispose to
Study Exclusion Criteria for Parts 2 and 3. 1. Subject with any clinically significant condition at the end of 8-week Induction
treatment from Part 1 Induction phase, and Part 2 Maintenance Phase that in the
opinion of investigator, would put the safety of the subject at risk through
participation, or which would affect the efficacy or safety analysis.
2. Subject who, in the opinion of the investigator or sponsor, is unlikely to be
cooperative or able to comply with study procedures, or any other condition which in
the opinion of the investigator would make the subject unsuitable for inclusion.