A Phase 3 Study to Investigate the Efficacy and Safety of SHR0302 With Moderately to Severely Active Ulcerative Colitis
Ulcerative Colitis
About this trial
This is an interventional treatment trial for Ulcerative Colitis
Eligibility Criteria
Inclusion Criteria:
Inclusion Criteria for Part 1
- Male or female subjects must be at least at ≥18 and ≤75 years of age
- Subject has at least a three-month history of Ulcerative Colitis diagnosis at baseline.
- Subject has active Ulcerative Colitis with a 9-point modified Mayo score of ≥ 5 at baseline, with an endoscopic subscore of ≥ 2
- Subject is deemed by the physician as having inadequate response, loss of response or intolerance to at least one conventional treatment (oral 5-ASA, immunosuppressants or corticosteroids), or was previously exposed to anti-TNF therapy (e.g., infliximab, adalimumab) or other biological treatment (e.g., vedolizumab) having
Discontinued the treatment for:
- Infliximab: a minimum of 8 weeks prior to baseline.
- Adalimumab: a minimum of 10 weeks prior to baseline.
- Ustekinumab: a minimum of 14 weeks prior to baseline.
- Vedolizumab: a minimum of 17 weeks prior to baseline.
Inclusion Criteria for Part 2 1. Subject has completed Part 1 and achieved clinical response at week 8
Inclusion Criteria for Part 3
1. Subject has completed the 8-week Part 1 and was classified as not meeting clinical response criteria. OR Subject has discontinued treatment early in the Maintenance phase due to disease worsening OR Subject has completed the Maintenance phase.
Study Exclusion Criteria for Part 1
Exclusion Criteria:
- Subject has a diagnosis of indeterminate colitis, or clinical findings suggestive of Crohn'sDisease.
- Subject with Ulcerative Colitis, which is confined to a proctitis (distal 15 cm or less).
- Treatment naïve subject diagnosed with Ulcerative Colitis (without previous exposure to any of the following therapies for UC treatment: oral 5-ASA, corticosteroids, immunosuppressants, or biological treatments).
- Subject is displaying clinical signs of ischemic colitis, fulminant colitis or toxic megacolon.
- Subject had previous surgery as a treatment for Ulcerative Colitis or likely to require surgery during the study period.
- Subject has evidence of pathogenic bowel infection. Subjects had Clostridium difficile or other intestinal infection within 30 days of screening endoscopy or test positive at screening for C.difficile toxin or other intestinal pathogens.
- Subject currently has or has a history of active tuberculosis (TB) or latent TB infection.
Subject is receiving any of the following therapies:
- Azathioprine/6-mercaptopurine, methotrexate, thalidomide within 7 days prior to baseline.
- Cyclosporine, mycophenolate, tacrolimus within 4 weeks prior to baseline.
- Interferon therapy within 8 weeks prior to baseline.
- Intravenous corticosteroids or rectally administered formulation of corticosteroids or 5- ASA within 2 weeks prior to baseline.
- Subject had any prior treatment with lymphocyte-depleting agents/therapies (such as CamPath® [alemtuzumab], alkylating agents [e.g., cyclophosphamide or chlorambucil], total lymphoid irradiation, etc.). Subjects who have received rituximab or other selective B lymphocyte depleting agents are eligible if they have not received such therapy for at least 1 year prior to baseline.
- Subject has previously received JAK inhibitors, such as tofacitinib, baricitinib, upadacitinib, filgotinib.
- Subject with evidence of clinically relevant laboratory abnormalities which may affect subject safety or interpretation of study results at screening
- Subject has a screening 12-lead ECG that demonstrates clinically relevant abnormalities
Subject currently has or had:
- A clinically significant infection within 1 month of baseline (e.g., those requiring hospitalization or parenteral antimicrobial therapy or have opportunistic infections).
- A history of more than one episode of herpes zoster, or disseminated zoster (single episode).
- Any infection otherwise judged by the investigator to have the potential for exacerbation by participation in the study.
- Any infection requiring antimicrobial therapy within 2 weeks of screening.
- Subject has current immunization with any live virus vaccine or history of immunization with any live virus vaccine within 8 weeks of baseline.
- Subject with a first-degree relative with a hereditary immunodeficiency.
- Subject with a history of any lymphoproliferative disorder (such as EBV-related lymphoproliferative disorder, as reported in some subjects on other immunosuppressive drugs), history of lymphoma, leukemia, multiple myeloma, or signs and symptoms that are suggestive of current lymphatic disease.
- Subject has any condition possibly affecting oral drug absorption e.g., gastrectomy, or clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. (Procedures such as gastric banding, gastric balloon that simply divide stomach into separate chambers, are NOT exclusionary.) Subject has undergone significant trauma or major surgery within 4 weeks of baseline.
- Women who are pregnant or lactating, or planning pregnancy while enrolled in the study. Male who plan to donate sperm during the study and within 30 days after the last dose of study drug.
- Subject who has a history of alcohol or drug abuse with less than 6 months of abstinence prior to baseline that in the opinion of the investigator will preclude participation in the study.
- Subject with malignancies or with a history of malignancies with exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin.
- Subject infected with human immunodeficiency virus (HIV) or hepatitis B or C viruses.
- Subject has received any investigational drug or device within 3 months, or 5 half-lives (if known) prior to baseline.
- Subject is receiving or expected to receive prohibited concomitant medication(s) in the 4 weeks prior to the first dose of study drug and through follow-up visit.
- Any other condition which in the opinion of the investigator would make the subject unsuitable for inclusion in the study.
- Subject with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including uncontrolled diabetes or thyroid disease), or hematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
- Subject with a history of thromboembolic events, including deep vein thromboses (DVT), pulmonary embolism (PE), and those with known inherited conditions that predispose to hypercoagulability.
Study Exclusion Criteria for Parts 2 and 3
- Subject with any clinically significant condition at the end of 8-week Induction treatment from Part 1 Induction phase, and Part 2 Maintenance Phase that in the opinion of investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis.
- Subject who, in the opinion of the investigator or sponsor, is unlikely to be cooperative or able to comply with study procedures, or any other condition which in the opinion of the investigator would make the subject unsuitable for inclusion.
Sites / Locations
- Digestive Health Specialists
- Om Research LLC
- Yale University
- IHS Health
- Dade Research Center
- Gastro Florida
- One Health Research Clinic Atlanta, LLC
- John Hopkins University
- Michigan Medical
- Research Institute of Michigan
- NY Scientific
- DiGiovanna Institute for Medical Education & Research
- University of North Carolina at Chapel Hill
- Charlotte Gastroenterology & Hepatology P.L.L.C
- DDSI
- Central Sooner Research
- Vanderbilt University Medical Center
- Omni Clinical Research
- UTMB Health
- University of Utah
- McGuire Research Institute
- IACT Health
- Advocate Aurora Health - Aurora St. Luke's Medical Center
- The First Affiliated Hospital of Bengbu Medical CollegeRecruiting
- Anhui Provincial HospitalRecruiting
- Beijing Military Area General Hospital/Seventh Medical Center of PLA General HospitalRecruiting
- Peking University First Hospital
- Peking University Third HospitalRecruiting
- Tsinghua University Changgung Hospital
- Army Medical Center of PLARecruiting
- Chongqing People's HospitalRecruiting
- The First Affiliated Hospital of Chongqing Medical UniversityRecruiting
- The First Affiliated Hospital of Fujian Medical UniversityRecruiting
- The First Affiliated Hospitial of Xiamen UniversityRecruiting
- Guangzhou First People's HospitalRecruiting
- The First Affiliated Hospital, Sun Yat-sen UniversityRecruiting
- The Sixth Affiliated Hospital of Sun Yat-Sen UniversityRecruiting
- Third Affiliated Hospital of Guangzhou Medical UniversityRecruiting
- Peking University Shenzhen HospitalRecruiting
- The First Affiliated Hospital of Guangxi Medical UniversityRecruiting
- The Second Hospital of Hebei Medical UniversityRecruiting
- The First Affiliated Hospital of Henan University of Science and TechnoloyRecruiting
- Henan Provincial People's HospitalRecruiting
- The First Affiliated Hospital of Zhengzhou UniversityRecruiting
- The Second Affiliated Hospital of Zhengzhou UniversityRecruiting
- Jingzhou First People's HospitalRecruiting
- Affiliated Taihe Hospital of Hubei University of MedicineRecruiting
- Renmin Hospital of Wuhan University
- The Second Xiangya Hospital of Central South UniversityRecruiting
- Xiangya Hospital Central South UniversityRecruiting
- Zhuzhou Central HospitalRecruiting
- Baotou Central HospitalRecruiting
- Huai'an First People's HospitalRecruiting
- Jiangsu Province Hospital
- Nanjing First HospitalRecruiting
- Nanjing General Hospital of Nanjing Military CommandRecruiting
- Zhongda Hospital Southeast UniversityRecruiting
- The First Affiliated Hospital of Soochow UniversityRecruiting
- Subei People's Hospital of Jiangsu provinceRecruiting
- Shengjing Hospital Of China Medical UniversityRecruiting
- The First Hospital of China Medical University
- Binzhou Medical University HospitalRecruiting
- Liaocheng People's HospitalRecruiting
- Huashan Hospital, Fudan UniversityRecruiting
- Longhua Hospital Shanghai University of Traditional Chinese Medicine
- Renji Hospital, Shanghai Jiaotong University School of Medicine
- Ruijin Hospital, Shanghai Jiaotong University School of MedicineRecruiting
- Shanghai Changhai HospitalRecruiting
- Shanghai East Hospital
- Shanghai General Hospital
- Shanghai Sixth People's Hospital
- Zhongshan Hospital Affiliated to Fudan UniversityRecruiting
- Shanxi Provincial People's Hospital
- The First Hospital of Shanxi Medical UniversityRecruiting
- West China Hospital Sichuan UniversityRecruiting
- Tianjin medical University General HospitalRecruiting
- Tianjin Union Medical CenterRecruiting
- The First Affiliated Hospital of Zhejiang University of Traditional Chinese MedicineRecruiting
- The Second Affiliated Hospital of Zhejiang University School of MedicineRecruiting
- Jinhua Municipal Central HospicalRecruiting
- Ningbo First HospitalRecruiting
- The First Affiliated Hospital of Wenzhou Medical UniversityRecruiting
- Curatio, Jsc
- JSC Infectious Diseases, AIDS and Clinical Immunology Research Center
- LTD Central University Clinic After Academic N. Kipshidze
- LTD The First Medical Center
- CLINSANTE Clinical Research Centre Ewa Galczak-Nowak, Malgorzata Trzaska
- MZ BADANIA Slowik Zymla General Partnership
- "Landa" Specialist Doctor's Offices
- PLEJADY Medical Centre
- AMED Medical Centre Branch in Lodz
- Oswiecim Clinical Trial Centre
- Private Healthcare Institution Specialist Clinics Termedica
- Dariusz Kleczkowski Specialist Medical Practice
- Torun Gastrology Centre "Gastromed"
- MDM Healthcare Centre
- WIP Warsaw IBD Point
- Medical Centre Oporow
- ETG Zamosc
- Communal Nonprofit Enterprise "Cherkasy Regional Hospital of Cherkasy Oblast Council"
- Regional Municipal Non-commercial Enterprise "Chernivtsi Emergency Medical Hospital"
- Public Non-Profit Enterprise "Regional Clinical Hospital under Ivano-Frankivsk Regional Council"
- Public Non-Profit Institution: O.O. Shalimov City Clinical Hospital #2 under Kharkiv City Council
- Public Non-Profit Enterprise "Khmelnytskyi Regional Hospital" under Khmelnytskyi Regional Council
- Clinical Hospital "Feofaniia"
- Medical Center "Consylium Medical"
- Medical Center OK!Clinic+ of the Company with Limited Liability International Institute of Clinical Research
- Municipal Enterprise "Volyn Regional Clinical Hospital" of Volyn Regional Council
- Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital"
- Public Non-Profit Enterprise under Sumy Regional Council "Sumy Regional Clinical Hospital"
- Communal Non-Commercial Enterprise: Vinnytsia City Clinical Hospital #1
- Public Non-Profit Enterprise "City Hospital #6" under Zaporizhia City Council
- "Medibor Plus" Llc
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Part 1 Active Experimental: SHR0302 Dose#1
Part 1 Placebo Comparator: Placebo
Part 2 Active Experimental: SHR0302 Dose#2
Part 2 Placebo Comparator: Placebo
Part 3 Active Experimental: SHR0302 Dose#2
SHR0302 Oral tablets taken once daily (QD) for 8 weeks SHR0302 Oral tablets taken once daily (QD)
Placebo Oral tablets taken once daily (QD) for 8 weeks
SHR0302 Oral tablets taken once daily (QD) for 44 weeks
Placebo Comparator: Maintenance Treatment Placebo Comparator: Placebo
SHR0302 Oral tablets taken once daily (QD) for 26 weeks