Study Evaluating ISM5411 Administered Orally to Subjects 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 is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics and clinical efficacy of ISM5411 in adult patients with active ulcerative colitis.

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: ISM5411 tablets; Drug: ISM5411 tablets; Drug: Placebo

Detailed Description

ISM5411 is a gut-restricted small-molecule prolyl hydroxylase (PHD) inhibitor. It can promote the expression of intestinal mucosal protective genes and maintain the integrity and functions of intestinal barrier together with anti-inflammation. It is expected to become a safe and effective therapy to overcome the shortcomings of traditional simple anti-inflammatory drugs.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yang Deng; Phone Number: +86 021-50831718; Email: Insilico-Clinicaltrial@insilico.ai

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Friendship Hospital, Capital Medical University
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China
      • Recruiting
      • The First Affiliated Hospital of Chongqing Medical University
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • The First Affiliated Hospital,Sun Yat-sen University
    • Guangzhou, Guangdong, China
      • Recruiting
      • Guangzhou First People's Hospital
    • Huizhou, Guangdong, China
      • Recruiting
      • Huizhou First Hospital
  • Guangxi
    • Nanning, Guangxi, China
      • Recruiting
      • The People's Hospital of Guangxi Zhuang Autonomous Region
  • Hebei
    • Shijiazhuang, Hebei, China
      • Recruiting
      • The Second Hospital of Hebei Medical University
  • Henan
    • Luoyang, Henan, China
      • Recruiting
      • The First Affiliated Hospital of Henan University of Science & Technology
    • Xinxiang, Henan, China
      • Recruiting
      • The First Affiliated Hospital of Xinxiang Medical University
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Renmin Hospital of Wuhan University
  • Hunan
    • Changsha, Hunan, China
      • Not yet recruiting
      • The Third Xiangya Hospital of Central South University
    • Hengyang, Hunan, China
      • Not yet recruiting
      • The First Affiliated Hospital of University of South China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Zhongda Hospital Southeast University
  • Jiangxi
    • Ganzhou, Jiangxi, China
      • Recruiting
      • The First Affiliated Hospital of Gannan Medical University
  • Jilin
    • Tonghua, Jilin, China
      • Recruiting
      • Meihekou Central Hospital
  • Liaoning
    • Shenyang, Liaoning, China
      • Recruiting
      • Shengjing Hospital Of China Medical University
  • Shandong
    • Binzhou, Shandong, China
      • Recruiting
      • Binzhou Medical University Hospital
    • Taian, Shandong, China
      • Recruiting
      • Tai 'an City Central Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Renji Hospital, Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai Municipality, China
      • Not yet recruiting
      • Longhua Hospital Shanghai University of Traditional Chinese Medicine
  • Shanxi
    • Taiyuan, Shanxi, China
      • Recruiting
      • First Hospital of Shanxi Medical University
    • Xian, Shanxi, China
      • Not yet recruiting
      • Xi'an Central Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • Sichuan Provincial People's Hospital
    • Chengdu, Sichuan, China
      • Recruiting
      • West China School of Medicine and West China Hospital Sichuan University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Recruiting
      • Tianjin People's Hospital
  • Yunnan
    • Kunming, Yunnan, China
      • Recruiting
      • The First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Lishui, Zhejiang, China
      • Not yet recruiting
      • Lishui Central Hospital
    • Wenzhou, Zhejiang, China
      • Recruiting
      • The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients assigned to Cohort 1 will receive ISM5411 tablets up to 12 weeks.	Drug: ISM5411 tablets; Dosage Form: Tablet; Frequency of administration: Orally QD.; Other Names: Garutadustat; Drug: ISM5411 tablets; Dosage Form: Tablet ; Frequency of administration: Orally QD.; Other Names: Garutadustat
Experimental: Patients assigned to Cohort 2 will receive ISM5411 tablets up to 12 weeks.	Drug: ISM5411 tablets; Dosage Form: Tablet; Frequency of administration: Orally QD.; Other Names: Garutadustat; Drug: ISM5411 tablets; Dosage Form: Tablet ; Frequency of administration: Orally QD.; Other Names: Garutadustat
Experimental: Patients assigned to Cohort 3 will receive ISM5411 tablets up to 12 weeks.	Drug: ISM5411 tablets; Dosage Form: Tablet; Frequency of administration: Orally QD.; Other Names: Garutadustat; Drug: ISM5411 tablets; Dosage Form: Tablet ; Frequency of administration: Orally QD.; Other Names: Garutadustat
Placebo Comparator: Patients assigned to Cohort 4 will receive placebo up to 12 weeks.	Drug: Placebo; Dosage Form: Tablet; Frequency of administration: Orally QD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of treatment-emergent adverse events (TEAEs) in each group.	To evaluate the safety and tolerability of ISM5411.	Week1 to Week12.
The rate of serious adverse events (SAEs) and adverse events (AEs) leading to discontinuation of treatment in each group.	To evaluate the safety and tolerability of ISM5411.	Up to 16 weeks.
Changes and comparisons of the following data for each group of subjects: vital signs, physical examination, laboratory test(blood routine, blood chemistry, urinalysis, coagulation function, etc.), ECG(Heart rate, RR, PR, QRS,QT, QTcF ), etc.	To evaluate the safety and tolerability of ISM5411.	Up to 16 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration (Cmax)	To evaluate pharmacokinetics (PK) of ISM5411 in moderately to severely active UC patients.	Week1 to Week12.
Peak plasma time (Tmax)	To evaluate PK of ISM5411 in moderately to severely active UC patients.	Week1 to Week12.
Area under the plasma concentration-time curve extrapolated from time zero to infinity (AUC0-inf).	To evaluate PK of ISM5411 in moderately to severely active UC patients.	Week1 to Week12.
Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t).	To evaluate PK of ISM5411 in moderately to severely active UC patients.	Week1 to Week12.
Terminal rate constant (λz)	To evaluate PK of ISM5411 in moderately to severely active UC patients.	Week1 to Week12.
Elimination half-life (t1/2)	To evaluate PK of ISM5411 in moderately to severely active UC patients.	Week1 to Week12.
Apparent volume of distribution (Vz/F)	To evaluate PK of ISM5411 in moderately to severely active UC patients.	Week1 to Week12.
Apparent clearance (CL/F)	To evaluate PK of ISM5411 in moderately to severely active UC patients.	Week1 to Week12.
Mean residence time (MRT)	To evaluate PK of ISM5411 in moderately to severely active UC patients.	Week1 to Week12.
Colonic tissue concentration (Ccolon)	To evaluate PK of ISM5411 in moderately to severely active UC patients.	Week1 to Week12.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The total number and proportion of subjects who achieve clinical remission.	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 12 postdose
The total number and proportion of subjects who achieve clinical response.	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 12 postdose.
The total number and proportion of subjects who achieve symptomatic remission.	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 12 postdose
Change from baseline (CFB) in modified Mayo Score and Mayo subscore (including rectal bleeding score [RBS], stool frequency score [SFS] and Mayo endoscopic score [MES]) .	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 12 postdose.
CFB in Robarts Histopathology Index (RHI) Score.	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 12 postdose.
The total number and proportion of subjects who achieve endoscopic response.	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 12 postdose.
The total number and proportion of subjects who achieve endoscopic remission.	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 12 postdose.
The total number and proportion of subjects who achieve histological response.	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 12 postdose.
The total number and proportion of subjects who achieve histological remission.	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 12 postdose
CFB in the concentration of fecal calprotectin (FC)	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients	At Week 2, Week 6, and Week 12 postdose.
CFB in the concentration of high-sensitivity C-reactive protein (hs-CRP) .	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 2, Week 6, and Week 12 postdose.
CFB in the expression level of erythropoietin (EPO) and vascular endothelial growth factor-A (VEGF-A) in serum (or plasma).	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	After Day 1 dosing (4 h, 8 h and 12 h) and at Week 2, Week 6, and Week 12 postdose.
CFB in the expression level of hypoxia-inducible factor-1α (HIF-1α) in colonic tissue.	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 12 postdose.
CFB in the concentration of fecal Neutrophil gelatinase-associated lipocalin-2 (NGAL/LCN-2).	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 2, Week 6, and Week 12 postdose.
CFB in the serum or plasma levels of proteomes related to inflammation using proteomics.	To evaluate the clinical efficacy of ISM5411 on disease activity by analyzing the symptoms, endoscopy, histopathology, and biomarkers in active UC patients.	At Week 6 and Week 12 postdose

Collaborators and Investigators

• Sponsor: InSilico Medicine Hong Kong Limited

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2025
• Primary Completion (Estimated): August 15, 2027
• Study Completion (Estimated): August 30, 2027

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Actual): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Inflammatory bowel disease (IBD); Prolyl hydroxylase (PHD) inhibitor; Ulcerative colitis（UC）
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Colitis; Colitis, Ulcerative; Inflammatory Bowel Diseases
• Other Study ID Numbers: ISM5411-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No