TQH3906 capsules for adults with moderate-to-severe ulcerative colitis or Crohn's disease

A Phase Ib Clinical Trial to Evaluate the Efficacy and Safety of TQH3906 in Adults With Moderately to Severely Active Ulcerative Colitis or Crohn's Disease

This trial will test whether taking TQH3906 capsules helps adults with moderate-to-severe ulcerative colitis or Crohn's disease control their symptoms over a 12-week treatment period.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 135 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 30 sites (Bengbu, Anhui and 29 other locations)
• Trial ID: NCT06754891 on ClinicalTrials.gov

What this trial studies

This Phase 1, randomized, double-blind, placebo-controlled 1:1:1 trial compares placebo, a 32 mg dose, and a 24 mg twice-daily dose of TQH3906 in adults with moderate-to-severe ulcerative colitis or Crohn's disease. The study plans to enroll 105 participants with up to a 4-week screening period, a 12-week treatment period, and a 4-week post-treatment follow-up. About half of enrolled participants will have failed conventional therapy and half will have failed biologic therapy, and investigators will collect safety, pharmacokinetic/pharmacodynamic (PK/PD), and early efficacy data. The phase begins after dose-escalation in the 24 mg twice-daily cohort and is designed to characterize tolerability and initial clinical effect compared with placebo.

Who should consider this trial

Good fit: Adults aged 18–75 with a confirmed diagnosis of moderate-to-severe ulcerative colitis or Crohn's disease who have failed or are intolerant to prior conventional or biologic therapies and meet medication-stabilization requirements are eligible.

Not a fit: Patients with mild disease, those outside the 18–75 age range, or those who are doing well on current therapies are unlikely to receive direct benefit from participation.

Why it matters

Potential benefit: If successful, TQH3906 could offer an additional oral treatment option to reduce inflammation and symptoms in people with moderate-to-severe inflammatory bowel disease.

How similar studies have performed: Other oral small-molecule therapies, such as some JAK inhibitors, have shown benefit in moderate-to-severe IBD, but TQH3906 is a novel compound with limited published clinical data to date.

Eligibility criteria

Inclusion Criteria:

* Age between 18-75 years (inclusive of both 18 and 75), regardless of gender.
* Diagnosed with ulcerative colitis or Crohn's disease for ≥3 months, as assessed by histological or endoscopic examination prior to screening.
* Active moderate to severe UC or CD.
* Subjects must have failed at least one of the following drug treatments for UC or CD or be intolerant: oral aminosalicylates, oral corticosteroids, immunosuppressants, biologics, etc.
* If subjects are using the following drugs for UC or CD at the time of screening, their treatment should be stabilized with oral aminosalicylates for at least 3 weeks before the first dose of the trial medication, or stabilized with oral systemic corticosteroids for at least 2 weeks before the first dose of the trial medication, and maintain a stable dose during the trial period.
* If oral aminosalicylate or combined hormone therapy has been discontinued recently, it must be discontinued for at least 2 weeks prior to the pre-randomization endoscopy.
* Subjects (including partners) are willing to voluntarily take appropriate and effective contraceptive measures from the time of screening until 3 months after the last administration of the study medication.
* Before the trial, understand in detail the nature, significance, potential benefits, possible inconveniences, and potential risks of the trial, understand the research procedures, and voluntarily sign the informed consent form.

Exclusion Criteria:

* Pregnant or lactating women.
* Lesions confined solely to the rectal segment within 15 cm of the anus.
* Subjects diagnosed with indeterminate colitis, radiation colitis, or ischemic colitis.
* Presence of severe complications such as local stricture, intestinal obstruction, intestinal perforation, major lower gastrointestinal hemorrhage, intestinal neoplastic changes or neoplastic potential, toxic megacolon; rectal/colonic polyps, or anal diseases that the investigator assesses may impact efficacy and safety evaluation.
* Subjects with current stomas, ileostomy-anal anastomoses, or fistulas, where the physician determines surgery or medical intervention may be required within 12 weeks of study entry, or where ileostomy or colostomy may be necessary.
* Subjects with extensive small bowel resection (\>100 cm) or diagnosed short bowel syndrome, or requiring total parenteral nutrition.
* Subjects with documented positive Clostridium difficile toxin (C. difficile) testing or polymerase chain reaction (PCR) testing.Polymerase Chain Reaction (PCR) test. If positive, the subject may be rescreened after appropriate treatment and retested no earlier than 7 days after treatment completion.
* Patients with confirmed cytomegalovirus-associated colitis must have undergone adequate treatment for at least 3 months prior to the screening endoscopy and must be symptom-free.
* Presence of abnormal seroviral status during the screening period:

a Active hepatitis, or hepatitis B surface antigen (HBsAg) positive with Hepatitis B Virus (HBV) DNA positive, or hepatitis B core antibody (HBcAb) positive with HBV-DNA positive, or Hepatitis C Virus (HCV) antibody positive with HCV-RNA positive; b Screening-period HIV antibody positive, or prior history of HIV infection; c. Positive treponemal antibody during screening without positive treponemal serological test (RPR or TRUST).

* History of active tuberculosis during screening or prior to enrollment, or detection of latent tuberculosis infection during screening (defined as T-cell Spot of Tuberculosis (T-SPOT.0) positive without clinical manifestations). (Note: Patients with latent tuberculosis infection may initiate preventive treatment according to guidelines for 1 month. To continue in the study, patients must agree to complete the prophylactic treatment regimen during the study period, avoiding rifampin therapy.
* History of severe herpes zoster or herpes simplex infections, including but not limited to herpes encephalitis, disseminated herpes simplex, or generalized herpes zoster.
* History of severe bacterial, fungal, or viral infection requiring hospitalization with intravenous antibiotics or antiviral therapy within 2 months prior to first dosing.
* Receipt of live vaccine within 4 weeks prior to first dosing or planned administration of live vaccine during the study period.
* Development of clinically significant infection during the screening period, including but not limited to upper respiratory tract infection, lower respiratory tract infection, herpes simplex, or herpes zoster requiring antibiotic or antiviral treatment.
* Presence of any major disease or unstable clinical condition (e.g., renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, psychiatric, neurological, immunologic, or locally active infection/infectious disease) deemed by the investigator to make participation in this study inappropriate.
* Suffering from angina pectoris, arrhythmia, or congestive heart failure requiring medication, or exhibiting clinically significant abnormalities on screening ECG.
* Abnormal screening laboratory tests:

  i. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times upper limit of normal (ULN); a Hemoglobin \< 90 g/L; b White blood cell count \< 3.0 × 10⁹/L; c Neutrophil count \< 1.0 × 10⁹/L; d Lymphocyte count \< 0.5 × 10⁹/L; e Platelet count \< 100 × 10⁹/L; f Total bilirubin \> 2 times ULN; g Other significant laboratory abnormalities deemed by the investigator to make the subject unsuitable for this study.
* Subjects with poorly controlled diabetes or diabetes with major complications (e.g., retinopathy or nephropathy).
* History of malignancy (including carcinoma in situ) or lymphoproliferative disorders within 5 years prior to first dosing.
* Within 8 weeks or 5 half-lives (whichever is longer) prior to the first dose, patients must have received ≤2 classes of biologics (e.g., anti-Tumor Necrosis Factor-alpha (TNF-α) agents are considered 1 class), including but not limited to anti-TNF-α and anti-α4β7 integrin agents.
* Patients who have received Janus Kinase (JAK) inhibitors or other small molecule inhibitors (excluding those targeting Tyrosine Kinase 2 (TYK2) or TYK2/JAK1) within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose may be enrolled if the washout period is satisfied.
* Previously received treatment with small-molecule drugs targeting the same TYK2 or TYK2/JAK1 target.
* Received fecal microbiota transplantation, cyclosporine, tacrolimus, mycophenolate mofetil, thalidomide, immunosuppressants, or similar medications within 4 weeks prior to first dose.
* Received any other investigational drug within 1 month or 5 half-lives (whichever is longer) prior to the first dose.
* Underwent surgery within 4 weeks prior to the first dose, or plans to undergo surgery during the study period.
* Received immunoglobulin or blood products within 4 weeks prior to the first dose.
* Use of potent CYP450 inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) within 4 weeks prior to first dose.
* Use of topical therapy (enemas or suppositories), intravenous corticosteroids, anti-UC or CD traditional Chinese medicine, anti-infective agents, or antidiarrheal medications.
* Received nonsteroidal anti-inflammatory drugs (NSAIDs) within 1 week prior to first dose (excluding topical NSAIDs and low-dose aspirin for cardiovascular protection).
* Organ transplant recipients requiring ongoing immunosuppressive therapy.
* Known allergy to any component of TQH3906 or history of severe drug hypersensitivity.
* History of substance abuse or positive urine drug screen.
* Any other reasonable medical, psychiatric, or social reason deemed by the investigator to preclude participation in this study.

Where this trial is running

Bengbu, Anhui and 29 other locations

• The First Affilliated Hospital of Bengbu Medical University — Bengbu, Anhui, China (Not_yet_recruiting)
• Gansu Wuwei Tumour Hospital — Wuwei, Gansu, China (Not_yet_recruiting)
• First affiliated hospital of guangzhou medical university — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Zhujiang Hospital, of Southern Medical University — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Huizhou First People's Hospital — Huizhou, Guangdong, China (Not_yet_recruiting)
• Heilongjiang provincial hospital — Harbin, Heilongjiang, China (Not_yet_recruiting)
• Luoyang Central Hospital (Zhengzhou University Affiliated Luoyang Central Hospital) — Luoyang, Henan, China (Not_yet_recruiting)
• Luoyang First People's Hospital — Luoyang, Henan, China (Not_yet_recruiting)
• Nanyang Second General Hospital — Nanyang, Henan, China (Not_yet_recruiting)
• Henan Provincial People's Hospital — Zhengzhou, Henan, China (Not_yet_recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Not_yet_recruiting)
• The Second Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Not_yet_recruiting)
• Union Hosiptal, Tongji Medical College, Huazhong University of Science And Technolocy — Wuhan, Hubei, China (Not_yet_recruiting)
• Renmin Hospital of Wuhan University — Wuhan, Hubei, China (Not_yet_recruiting)
• Hunan Provincial People's Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• The Second Xiangya Hospital of Central South University — Changsha, Hunan, China (Not_yet_recruiting)
• 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)
• Jiangsu Provincial People's Hospital — Nanjing, Jiangsu, China (Not_yet_recruiting)
• The first hospital of Jilin University — Changchun, Jilin, China (Not_yet_recruiting)
• Meihekou Central Hospital — Meihekou, Jilin, China (Not_yet_recruiting)
• Shengjing Hospital oh China Medical University — Shenyang, Liaoning, China (Not_yet_recruiting)
• The Second School of Clinical Medicine of Shandong First Medical University — Taishan, Shandong, China (Not_yet_recruiting)
• Ruijin Hospital, Shanghai Jiaotong University School of Medicine — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• Shanxi Provincial People's Hospital — Taiyuan, Shanxi, China (Not_yet_recruiting)
• The TCM Affiliated Hospital of Southwest Medical University — Luzhou, Sichuan, China (Recruiting)
• Tianjin People's Hospital — Tianjin, Tianjin Municipality, China (Not_yet_recruiting)
• The First Affiliated Hospital of Xinjiang Medical University — Ürümqi, Xinjiang, China (Recruiting)
• The First Affiliated Hospital of Kunming Medical University — Kunming, Yunnan, China (Not_yet_recruiting)
• Taizhou Municipal Hospital — Taizhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Xiaowei Liu, Postdoctoral researcher

Conditions Inflammatory Bowel Diseases