Oral ISM5411 for adults with active ulcerative colitis (BETHESDA)

A Phase IIa, Multicenter, Randomized, Double-blind, Placebo-controlled, Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of ISM5411 in Adult Patients With Active Ulcerative Colitis

This trial will test whether taking oral ISM5411 is safe and helps adults with active ulcerative colitis.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: InSilico Medicine Hong Kong Limited (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 28 sites (Beijing, Beijing Municipality and 27 other locations)
• Trial ID: NCT07265570 on ClinicalTrials.gov

What this trial studies

ISM5411 is a gut-restricted small-molecule prolyl hydroxylase (PHD) inhibitor intended to boost intestinal mucosal protective genes, support barrier integrity, and reduce inflammation. This multicenter, randomized, double-blind, placebo-controlled Phase 2 study gives adults with active ulcerative colitis oral ISM5411 or matching placebo and collects safety, tolerability, pharmacokinetics, and clinical efficacy data. Participants are treated and monitored at several major hospitals in China with blinded outcome assessments. Results will inform whether ISM5411 warrants larger trials and help define dose and safety parameters.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18–75 with a documented diagnosis of active ulcerative colitis for at least three months who are nonpregnant/nonlactating, agree to required contraception, and meet the protocol's medication and health criteria.

Not a fit: Patients with inactive or very mild disease, those who are pregnant or breastfeeding, or those with exclusionary medical conditions or incompatible medications are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, ISM5411 could offer a gut-targeted therapy that better protects the intestinal lining and reduces inflammation with potentially fewer systemic side effects than traditional anti-inflammatory drugs.

How similar studies have performed: PHD inhibition is a relatively novel approach for inflammatory bowel disease: it has shown promising mucosal-protective effects in preclinical studies and limited early clinical work, but clear clinical success in ulcerative colitis has not yet been established.

Eligibility criteria

Inclusion Criteria:

1. Subject who fully understand the content, process and possible adverse events of the study and capable of giving written informed consent form (ICF).
2. Female subjects must be nonpregnancy and nonlactating. Subjects (male or female) are willing to take medically approved effective contraceptive measures from the screening period to 3 months after the last administration and have no sperm or egg donation plan during the study period and within 3 months after the last dose.
3. Male or female between 18 and 75 years of age (inclusive), at the time of signing the ICF.
4. Subject has a diagnosis of ulcerative colitis for at least 3 months prior to colonoscopy during the screening period, and meets the criteria defined in the current protocol.
5. If the subjects have concomitant medication defined in the current protocol, they must meet the relevant criteria to be enrolled.
6. If the subjects have discontinued medication defined in the current protocol, they must meet the relevant criteria to be enrolled.

Exclusion Criteria:

1. 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.
2. Subjects with previously diagnosed but uneradicated or current gastrointestinal dysplasia.
3. 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.
4. 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.
5. 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.
6. 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.
7. Subjects who have received the relevant treatments defined in the protocol.
8. Subjects with recurrent or disseminated (even if single episode) herpes zoster, or cytomegalovirus infection.
9. Subjects who have the risks of tuberculosis defined in the protocol.
10. Subjects have any of the infection defined in the protocol.
11. 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).
12. 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.
13. 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).
14. 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.
15. 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.
16. Any abnormal results defined in the protocol were identified during the screening period.
17. Subjects with poorly controlled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg) despite medication at screening.
18. Subjects have a clinically significant abnormal ECG at screening, including QTcF \> 450 msec for males and \> 470 msec for females.
19. Subjects have difficulty in venous blood collection or history of acupuncture syncope reaction or blood phobia.
20. 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.
21. 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.
22. 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.
23. 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.

Where this trial is running

Beijing, Beijing Municipality and 27 other locations

• Beijing Friendship Hospital, Capital Medical University — Beijing, Beijing Municipality, China (Recruiting)
• The First Affiliated Hospital of Chongqing Medical University — Chongqing, Chongqing Municipality, China (Recruiting)
• Guangzhou First People's Hospital — Guangzhou, Guangdong, China (Recruiting)
• The First Affiliated Hospital,Sun Yat-sen University — Guangzhou, Guangdong, China (Recruiting)
• Huizhou First Hospital — Huizhou, Guangdong, China (Recruiting)
• The People's Hospital of Guangxi Zhuang Autonomous Region — Nanning, Guangxi, China (Recruiting)
• The Second Hospital of HeBei Medical University — Shijiazhuang, Hebei, China (Recruiting)
• The First Affiliated Hospital of Henan University of Science & Technology — Luoyang, Henan, China (Recruiting)
• The First Affiliated Hospital of Xinxiang Medical University — Xinxiang, Henan, China (Recruiting)
• Renmin Hospital of Wuhan University — Wuhan, Hubei, China (Recruiting)
• The Third Xiangya Hospital of Central South University — Changsha, Hunan, China (Not_yet_recruiting)
• The First Affiliated Hospital of University of South China — Hengyang, Hunan, China (Not_yet_recruiting)
• ZhongDa Hospital Southeast University — Nanjing, Jiangsu, China (Recruiting)
• The First Affiliated Hospital of Gannan Medical University — Ganzhou, Jiangxi, China (Recruiting)
• Meihekou Central Hospital — Tonghua, Jilin, China (Recruiting)
• Shengjing Hospital of China Medical University — Shenyang, Liaoning, China (Recruiting)
• Binzhou Medical University Hospital — Binzhou, Shandong, China (Recruiting)
• Tai 'an City Central Hospital — Taian, Shandong, China (Recruiting)
• Longhua Hospital Shanghai University of Traditional Chinese Medicine — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• Renji Hospital, Shanghai Jiaotong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)
• First Hospital of Shanxi Medical University — Taiyuan, Shanxi, China (Recruiting)
• Xi'an Central Hospital — Xian, Shanxi, China (Not_yet_recruiting)
• Sichuan Provincial People's Hospital — Chengdu, Sichuan, China (Recruiting)
• West China School of Medicine and West China Hospital Sichuan University — Chengdu, Sichuan, China (Recruiting)
• Tianjin People's Hospital — Tianjin, Tianjin Municipality, China (Recruiting)
• The First Affiliated Hospital of Kunming Medical University — Kunming, Yunnan, China (Recruiting)
• Lishui Central Hospital — Lishui, Zhejiang, China (Not_yet_recruiting)
• The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University — Wenzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Yang Deng

Conditions Ulcerative Colitis; Prolyl hydroxylase inhibitor; Ulcerative colitis（UC）; Inflammatory bowel disease