A Phase 3 Study to Investigate the Efficacy and Safety of SHR0302 With Moderately to Severely Active Ulcerative Colitis
- Registration Number
- NCT05181137
- Lead Sponsor
- Reistone Biopharma Company Limited
- Brief Summary
This is a randomized, double-blind, placebo-controlled, multicenter Phase 3 study that will enroll approximately 368 subjects aged 18 to 75 years old with Moderately to Severely Active Ulcerative Colitis.
- Detailed Description
This study consists of a screening period followed by a placebo-controlled Part 1 phase and then a placebo-controlled Part 2 phase. An open label Part 3 phase is open to subjects who: complete the Part 2, are considered non-responders following the Part 1, or have disease worsening during Part 2.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 368
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
- 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
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 Placebo Comparator: Placebo Placebo Placebo Oral tablets taken once daily (QD) for 8 weeks Part 1 Active Experimental: SHR0302 Dose#1 SHR0302 SHR0302 Oral tablets taken once daily (QD) for 8 weeks SHR0302 Oral tablets taken once daily (QD) Part 3 Active Experimental: SHR0302 Dose#2 SHR0302 SHR0302 Oral tablets taken once daily (QD) for 26 weeks Part 2 Active Experimental: SHR0302 Dose#2 SHR0302 SHR0302 Oral tablets taken once daily (QD) for 44 weeks Part 2 Placebo Comparator: Placebo Placebo Placebo Comparator: Maintenance Treatment Placebo Comparator: Placebo
- Primary Outcome Measures
Name Time Method Clinical remission at week 8 (Part 1) 8 weeks The percentage of subjects in clinical remission at week 8.
Clinical remission at week 52 (Part 2) 52 weeks The percentage of subjects in clinical remission at week 52.
- Secondary Outcome Measures
Name Time Method Endoscopic remission at week 8 (Part 1) 8 weeks The percentage of subjects with endoscopic remission at week 8.
Clinical response at week 8 (Part 1) 8 weeks The percentage of subjects with clinical response at week 8.
Change in total Mayo score and 9-point modified Mayo score at week 8 (Part 1) 8 weeks Change in total Mayo score and 9-point modified Mayo score at week 8.
Change from baseline in partial Mayo score at week 2, 4, and 8 (Part 1) 8 weeks Change from baseline in partial Mayo score at week 2, 4, and 8.
Change from baseline in partial Mayo score at week 12, 16, 24, 32, 40, and 52 (Part 2) 52 weeks Change from baseline in partial Mayo score at week 12, 16, 24, 32, 40, and 52.
Subjects with endoscopic remission (Part 2) 52 weeks The percentage of subjects with endoscopic remission at week 52.
Subjects with clinical response at week 52 (Part 2) 52 weeks The percentage of subjects with clinical response at week 52.
Change in total Mayo score and 9-point modified Mayo score at week 52 (Part 2) 52 weeks Change in total Mayo score and 9-point modified Mayo score at week 52.
Subjects in corticosteroid-free remission at week 52 (Part 2) 52 weeks Percentage of subjects in corticosteroid-free remission at week 52.
Subjects who maintain clinical remission at week 52 (Part 2) 52 weeks Percentage of subjects who maintain clinical remission at week 52
Subjects in clinical remission per partial Mayo score at week E26 (Part 3) 26 weeks (extension) The percentage of subjects in clinical remission per partial Mayo score at week E26.
Subjects in corticosteroid-free remission per Partial Mayo score at week E26 (Part 3) 26 weeks (extension) The percentage of subjects in corticosteroid-free remission per Partial Mayo score at week E26.
Change from baseline in Partial Mayo score at week E2, E12, and E26 (Part 3) 26 weeks (extension) Change from baseline in Partial Mayo score at week E2, E12, and E26.
Trial Locations
- Locations (113)
Zhongda Hospital Southeast University
🇨🇳Nanjing, Jiangsu, China
Clinical Hospital "Feofaniia"
🇺🇦Kyiv, Ukraine
Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital"
🇺🇦Lviv, Ukraine
Medical Centre Oporow
🇵🇱Wroclaw, Poland
JSC Infectious Diseases, AIDS and Clinical Immunology Research Center
🇬🇪Tbilisi, Georgia
Public Non-Profit Enterprise "Khmelnytskyi Regional Hospital" under Khmelnytskyi Regional Council
🇺🇦Khmelnytskyi, Ukraine
Public Non-Profit Enterprise "City Hospital #6" under Zaporizhia City Council
🇺🇦Zaporizhia, Ukraine
Regional Municipal Non-commercial Enterprise "Chernivtsi Emergency Medical Hospital"
🇺🇦Chernivtsi, Ukraine
Yale University
🇺🇸New Haven, Connecticut, United States
CLINSANTE Clinical Research Centre Ewa Galczak-Nowak, Malgorzata Trzaska
🇵🇱Bydgoszcz, Poland
"Landa" Specialist Doctor's Offices
🇵🇱Krakow, Poland
Public Non-Profit Institution: O.O. Shalimov City Clinical Hospital #2 under Kharkiv City Council
🇺🇦Kharkiv, Ukraine
LTD The First Medical Center
🇬🇪Tbilisi, Georgia
AMED Medical Centre Branch in Lodz
🇵🇱Lodz, Poland
Public Non-Profit Enterprise "Regional Clinical Hospital under Ivano-Frankivsk Regional Council"
🇺🇦Ivano-Frankivsk, Ukraine
Oswiecim Clinical Trial Centre
🇵🇱Oswiecim, Poland
Digestive Health Specialists
🇺🇸Dothan, Alabama, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
IHS Health
🇺🇸Kissimmee, Florida, United States
One Health Research Clinic Atlanta, LLC
🇺🇸Norcross, Georgia, United States
Dade Research Center
🇺🇸Miami, Florida, United States
Omni Clinical Research
🇺🇸Houston, Texas, United States
Central Sooner Research
🇺🇸Oklahoma City, Oklahoma, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Gastro Florida
🇺🇸Pinellas Park, Florida, United States
Om Research LLC
🇺🇸Lancaster, California, United States
Michigan Medical
🇺🇸Ann Arbor, Michigan, United States
John Hopkins University
🇺🇸Columbia, Maryland, United States
DiGiovanna Institute for Medical Education & Research
🇺🇸North Massapequa, New York, United States
Research Institute of Michigan
🇺🇸Chesterfield, Michigan, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Charlotte Gastroenterology & Hepatology P.L.L.C
🇺🇸Charlotte, North Carolina, United States
DDSI
🇺🇸Oklahoma City, Oklahoma, United States
UTMB Health
🇺🇸League City, Texas, United States
The First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, Anhui, China
Advocate Aurora Health - Aurora St. Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
McGuire Research Institute
🇺🇸Richmond, Virginia, United States
IACT Health
🇺🇸Suffolk, Virginia, United States
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
Beijing Military Area General Hospital/Seventh Medical Center of PLA General Hospital
🇨🇳Beijing, Beijing, China
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
Tsinghua University Changgung Hospital
🇨🇳Beijing, Beijing, China
Army Medical Center of PLA
🇨🇳Chongqing, Chongqing, China
Chongqing People's Hospital
🇨🇳Chongqing, Chongqing, China
The First Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
Guangzhou First People's Hospital
🇨🇳Guangzhou, Guangdong, China
The Sixth Affiliated Hospital of Sun Yat-Sen University
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospitial of Xiamen University
🇨🇳Xiamen, Fujian, China
The First Affiliated Hospital, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Third Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Peking University Shenzhen Hospital
🇨🇳Shenzhen, Guangdong, China
The Second Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
The First Affiliated Hospital of Henan University of Science and Technoloy
🇨🇳Luoyang, Henan, China
The Second Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Hena, China
Henan Provincial People's Hospital
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Jingzhou First People's Hospital
🇨🇳Jingzhou, Hubei, China
Affiliated Taihe Hospital of Hubei University of Medicine
🇨🇳Shiyan, Hubei, China
Zhuzhou Central Hospital
🇨🇳Zhuzhou, Hunan, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Xiangya Hospital Central South University
🇨🇳Changsha, Hunan, China
Renmin Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
Huai'an First People's Hospital
🇨🇳Huai'an, Jiangsu, China
Baotou Central Hospital
🇨🇳Baotou, Inner Mongolia, China
Nanjing General Hospital of Nanjing Military Command
🇨🇳Nanjing, Jiangsu, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
Nanjing First Hospital
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Subei People's Hospital of Jiangsu province
🇨🇳Yangzhou, Jiangsu, China
Shengjing Hospital Of China Medical University
🇨🇳Shenyang, Liaoning, China
Binzhou Medical University Hospital
🇨🇳Binzhou, Shandong, China
Huashan Hospital, Fudan University
🇨🇳Shanghai, Shanghai, China
Longhua Hospital Shanghai University of Traditional Chinese Medicine
🇨🇳Shanghai, Shanghai, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Liaocheng People's Hospital
🇨🇳Liaocheng, Shandong, China
Renji Hospital, Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Shanghai Changhai Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai East Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai General Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai Sixth People's Hospital
🇨🇳Shanghai, Shanghai, China
Shanxi Provincial People's Hospital
🇨🇳Shanxi, Shanxi, China
Zhongshan Hospital Affiliated to Fudan University
🇨🇳Shanghai, Shanghai, China
The First Hospital of Shanxi Medical University
🇨🇳Taiyuan, Shanxi, China
Tianjin Union Medical Center
🇨🇳Tianjin, Tianjin, China
West China Hospital Sichuan University
🇨🇳Chengdu, Sichuan, China
Tianjin medical University General Hospital
🇨🇳Tianjin, Tianjin, China
Ningbo First Hospital
🇨🇳Ningbo, Zhejiang, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Jinhua Municipal Central Hospical
🇨🇳Jinhua, Zhejiang, China
Curatio, Jsc
🇬🇪Tbilisi, Georgia
LTD Central University Clinic After Academic N. Kipshidze
🇬🇪Tbilisi, Georgia
MZ BADANIA Slowik Zymla General Partnership
🇵🇱Knurow, Poland
PLEJADY Medical Centre
🇵🇱Krakow, Poland
Private Healthcare Institution Specialist Clinics Termedica
🇵🇱Poznan, Poland
Dariusz Kleczkowski Specialist Medical Practice
🇵🇱Sopot, Poland
Torun Gastrology Centre "Gastromed"
🇵🇱Torun, Poland
ETG Zamosc
🇵🇱Zamosc, Poland
MDM Healthcare Centre
🇵🇱Warsaw, Poland
WIP Warsaw IBD Point
🇵🇱Warsaw, Poland
Communal Nonprofit Enterprise "Cherkasy Regional Hospital of Cherkasy Oblast Council"
🇺🇦Cherkasy, Ukraine
Municipal Enterprise "Volyn Regional Clinical Hospital" of Volyn Regional Council
🇺🇦Lutsk, Ukraine
Medical Center "Consylium Medical"
🇺🇦Kyiv, Ukraine
Medical Center OK!Clinic+ of the Company with Limited Liability International Institute of Clinical Research
🇺🇦Kyiv, Ukraine
Public Non-Profit Enterprise under Sumy Regional Council "Sumy Regional Clinical Hospital"
🇺🇦Sumy, Ukraine
Communal Non-Commercial Enterprise: Vinnytsia City Clinical Hospital #1
🇺🇦Vinnytsia, Ukraine
"Medibor Plus" Llc
🇺🇦Zhytomyr, Ukraine
NY Scientific
🇺🇸Brooklyn, New York, United States
Peking University First Hospital
🇨🇳Beijing, Beijing, China