Study Evaluating ISM5411 Administered Orally to Subjects With Active Ulcerative Colitis (BETHESDA)

Exclusion Criteria23

• Subjects have suspected or diagnosed Crohn's disease (CD), undefined colitis, ischemic colitis, fulminant colitis, toxic megacolon, radiation colitis, gastrointestinal perforation (other than appendicitis or penetrating injury), diverticular disease associated with colitis, enterophthisis, abdominal abscess or fistula, etc.
• Subjects with previously diagnosed but uneradicated or current gastrointestinal dysplasia.
• Subjects have received surgery for UC or any other type of major intestinal surgery (i.e., surgical procedure requiring general anesthesia) or are likely to require related surgery during the study.
• Subjects have evidence of a pathogenic intestinal infection, or have a Clostridium Difficile infection or other intestinal infection within 30 days prior to the screening endoscopy or have tested positive for Clostridium Difficile toxins or other intestinal pathogens at the screening period.
• Subjects have chronic recurring infection and/or active viral infection that, based on the investigator's clinical assessment, make them an unsuitable candidate for the study.
• Subjects who are unable to take oral medications and/or have an impact on absorption of medication due to severe malnutrition or disease and surgery, etc., or who are currently receiving or plan to receive total parenteral nutrition (TPN) during the study period.
• Subjects who have received the relevant treatments defined in the protocol.
• Subjects with recurrent or disseminated (even if single episode) herpes zoster, or cytomegalovirus infection.
• Subjects who have the risks of tuberculosis defined in the protocol.
• Subjects have any of the infection defined in the protocol.
• Subjects who are known to be allergic to the investigational product or any components of it or who have allergic constitution (allergy to multiple drugs or foods).
• Subjects have unstable or uncontrolled and clinically significant allergic (except for untreated, asymptomatic, seasonal allergies), hematological, endocrine/metabolic, coagulation, immunologic, pulmonary, cardiovascular, hepatic (expect hepatic steatohepatitis), digestion system (expect UC), genitourinary, psychiatric, oncologic or neurological disease or other medical disorder that would make them ineligible for the study.
• Subjects have concomitant illness that in the opinion of the investigator, are likely to require systemic glucocorticosteroid therapy during the study (e.g., moderate to severe asthma).
• Subjects have received major organ surgery (except needle biopsy, tracheotomy, gastrotomy, etc.) or significant trauma within 28 days prior to randomization or is likely to require related surgery during the study.
• Subjects have history of any malignancy within 5 years of screening, except for successfully treated nonmelanoma skin cancer (NMSC), skin basal cell carcinoma, or localized carcinoma in situ of the cervix.
• Any abnormal results defined in the protocol were identified during the screening period.
• Subjects have a clinically significant abnormal ECG at screening, including QTcF \> 450 msec for males and \> 470 msec for females.
• Subjects have difficulty in venous blood collection or history of acupuncture syncope reaction or blood phobia.
• Subjects have contraindications to colonoscopy, including but not limited to gastrointestinal fistulas, early post abdominal surgery, severe coagulopathy, large abdominal aneurysms, or any condition that the investigator determines significantly increases the risk of colonoscopy complications.
• Subjects have a history of alcohol or drug abuse within 3 months of screening, according to the judgement of the investigator. Alcohol abuse refers to consuming alcohol at least twice per day or more than 14 units of alcohol per week.
• Subjects are unable to maintain smoking and alcohol abstinence during the study.
• Subjects have participated in other clinical trials of other drugs or medical devices within 30 days prior to screening period and have already received the investigational product, or are currently participating in another clinical trial of a drug or medical device.
• Subjects are deemed by the investigator to be inappropriate for the study; or have any condition which would confound or interfere with the evaluation of the safety, tolerability, or PK of the investigational drug; or are unable or unwilling to comply with the study protocol.