Ensayos clínicos

Inclusion Criteria:

• Male or female and at least 18 years of age at screening.
• Has a history of UC for at least 3 months prior to screening (with involvement beyond the rectum to at least 15 cm from the anal verge).
• Has moderate-to-severely active UC, as defined by a Mayo endoscopic subscore of ≥ 2 points and an adapted Mayo score between 4 - 9 points, inclusive.
• Is corticosteroid-dependent or has demonstrated inadequate response, or intolerance to conventional therapy (aminosalicylates, corticosteroids, immunomodulators) or biologics.
• If subject is currently receiving oral aminosalicylate (e.g., mesalamine products, balsalazide, or sulfasalazine):
• Subject is eligible provided the subject has been on it at a stable dose for ≥ 4 weeks prior to Day 1.
• During the Study and for 7 days after receiving the last dose of the Study drug, females of childbearing potential or men capable of fathering children must agree to use highly effective birth control measures (failure rate < 1% when used consistently and correctly) or agree to abstain from sexual intercourse. Females of childbearing potential must test negative for pregnancy at screening and at Day 1.
• All male subjects must agree to refrain from semen donation during the Study and for 7 days after the last dose of Study drug.
• Must be able and willing to adhere to the Study visit schedule and comply with other protocol requirements.
• Are capable of providing informed consent, which must be obtained prior to any Study-related procedures.

Inclusion Criteria for Extended Induction (additional 8 weeks):

• Did not meet criteria for clinical response by adapted Mayo score using centrally read endoscopic subscore at Week 8a.

Inclusion Criteria for Maintenance Study:

• Must have met the criteria for a clinical response by adapted Mayo score using centrally read endoscopic subscore during Induction at Week 8a or during Extended Induction Study at Week 16.

Exclusion Criteria:

• Has symptoms suggestive of fulminant colitis, megacolon or intestinal perforation.
• Has primary sclerosing cholangitis (PSC).
• Likely to require surgery for UC or other major surgeries.
• Has had a clinically significant, as deemed by the investigator, prior intestinal resection for UC or for other gastrointestinal diseases (e.g., that may have resulted in chronic diarrhea)
• Has previously received / is currently receiving prohibited medications within specified timeframe.
• Is refractory to 3 biologics with ≥ 2 mechanisms of action.
• Has a current bacterial, parasitic, fungal, or viral infection.
• Has clinically significant abnormalities in laboratory evaluations.
• Has had any prior exposure to an approved Janus kinase (JAK) inhibitor or potential exposure to an investigational JAK inhibitor that was stopped due to intolerance or lack of efficacy.
• Are pregnant, lactating, breastfeeding or planning to become pregnant during the Study or within 7 days after the last dose of Study Drug.
• Has known moderate or severe hepatic impairment (e.g., Child-Pugh Class B or C).
• Has clinically significant abnormalities in the results of laboratory evaluations at screening visit as determined by the investigator, including:
  • AST, ALT, or alkaline phosphatase ≥ 2 x the upper limit of normal (ULN);
  • Total bilirubin > 2 x ULN (unless diagnosis of Gilbert’s syndrome);
  • Creatinine clearance as calculated by the Cockcroft-Gault formula < 30 mL/min;
  • Total white blood cell count (WBC) < 3 x 10^9 /L;
  • Absolute neutrophil count < 1.5 x 10^9 /L;
  • Absolute lymphocyte count < 0.8 x 10^9 /L;
  • Hemoglobin < 8 g/dL; or
  • Platelet count < 100 x 10^9 /L.
• Has a clinically significant abnormal electrocardiogram (ECG) at screening, including QTcF > 450 msec for males and > 470 msec for females.
• Has unstable or uncontrolled and clinically significant condition/disease that would compromise subject safety or confound Study safety assessment as determined by the investigator at screening and Day 1.
• Has known hypersensitivity to excipients or contents of the Study drug.
• Has participated in another clinical trial of an investigational drug (or medical device) within 30 days prior to Screening or 5 x the half-life of the investigational drug, whichever is longer, or is currently participating in another trial of an investigational drug (or medical device).
• Have or has a history of alcohol or drug abuse within 1 year of screening, per the judgment of the investigator.
• Has a current, or history of, malignancy requiring radiation or pharmacologic treatment within 5 years prior to screening, except for completely resected basal cell carcinoma or squamous cell carcinoma of the skin without recurrence for ≥ 1 year, cervical carcinoma in situ that has been adequately treated and without recurrence for ≥ 5 years.
• Is deemed by the investigator to be inappropriate for this Study; or has any condition which would confound or interfere with the evaluation of the safety, tolerability, or PK of the investigational drug; or is unable or unwilling to comply with the Study protocol.