Clinical trial NCT05181137: A Phase 3 Study to Investigate the Efficacy and Safety of SHR0302 With Moderately to Severely Active Ulcerative Colitis
Official title: A Phase 3 Study to Evaluate the Efficacy and Long-term Safety of SHR0302 Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ulcerative Colitis
Lead sponsor: Reistone Biopharma Company Limited
Sponsor class: INDUSTRY
First posted: 2022-01-06
Enrollment: 368
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

Inclusion Criteria for Part 1

1. Male or female subjects must be at least at ≥18 and ≤75 years of age
2. Subject has at least a three-month history of Ulcerative Colitis diagnosis at baseline.
3. Subject has active Ulcerative Colitis with a 9-point modified Mayo score of ≥ 5 at baseline, with an endoscopic subscore of ≥ 2
4. 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:

1. Subject has a diagnosis of indeterminate colitis, or clinical findings suggestive of Crohn'sDisease.
2. Subject with Ulcerative Colitis, which is confined to a proctitis (distal 15 cm or less).
3. 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).
4. Subject is displaying clinical signs of ischemic colitis, fulminant colitis or toxic megacolon.
5. Subject had previous surgery as a treatment for Ulcerative Colitis or likely to require surgery during the study period.
6. 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.
7. Subject currently has or has a history of active tuberculosis (TB) or latent TB infection.
8. 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.
9. 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.
10. Subject has previously received JAK inhibitors, such as tofacitinib, baricitinib, upadacitinib, filgotinib.
11. Subject with evidence of clinically relevant laboratory abnormalities which may affect subject safety or interpretation of study results at screening
12. Subject has a screening 12-lead ECG that demonstrates clinically relevant abnormalities
13. 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.
14. Subject has current immunization with any live virus vaccine or history of immunization with any live virus vaccine within 8 weeks of baseline.
15. Subject with a first-degree relative with a hereditary immunodeficiency.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. Subject infected with human immunodeficiency virus (HIV) or hepatitis B or C viruses.
22. Subject has received any investigational drug or device within 3 months, or 5 half-lives (if known) prior to baseline.
23. 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.
24. Any other condition which in the opinion of the investigator would make the subject unsuitable for inclusion in the study.
25. 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.
26. 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

1. 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.
2. 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.

Primary outcomes:
measure: Clinical remission at week 8 (Part 1)
timeFrame: 8 weeks
measure: Clinical remission at week 52 (Part 2)
timeFrame: 52 weeks
Secondary outcomes:
measure: Endoscopic remission at week 8 (Part 1)
timeFrame: 8 weeks
measure: Clinical response at week 8 (Part 1)
timeFrame: 8 weeks
measure: Change from baseline in partial Mayo score at week 2, 4, and 8 (Part 1)
timeFrame: 8 weeks
measure: Change in total Mayo score and 9-point modified Mayo score at week 8 (Part 1)
timeFrame: 8 weeks
measure: Subjects with endoscopic remission (Part 2)
timeFrame: 52 weeks
measure: Subjects with clinical response at week 52 (Part 2)
timeFrame: 52 weeks
measure: Change from baseline in partial Mayo score at week 12, 16, 24, 32, 40, and 52 (Part 2)
timeFrame: 52 weeks
measure: Change in total Mayo score and 9-point modified Mayo score at week 52 (Part 2)
timeFrame: 52 weeks
measure: Subjects in corticosteroid-free remission at week 52 (Part 2)
timeFrame: 52 weeks
measure: Subjects who maintain clinical remission at week 52 (Part 2)
timeFrame: 52 weeks
measure: Subjects in clinical remission per partial Mayo score at week E26 (Part 3)
timeFrame: 26 weeks (extension)
measure: Subjects in corticosteroid-free remission per Partial Mayo score at week E26 (Part 3)
timeFrame: 26 weeks (extension)
measure: Change from baseline in Partial Mayo score at week E2, E12, and E26 (Part 3)
timeFrame: 26 weeks (extension)
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialists
state: Alabama
city: Lancaster
country: United States
facility: Om Research LLC
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Kissimmee
country: United States
facility: IHS Health
state: Florida
city: Miami
country: United States
facility: Dade Research Center
state: Florida
city: Pinellas Park
country: United States
facility: Gastro Florida
state: Florida
city: Norcross
country: United States
facility: One Health Research Clinic Atlanta, LLC
state: Georgia
city: Columbia
country: United States
facility: John Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: Michigan Medical
state: Michigan
city: Chesterfield
country: United States
facility: Research Institute of Michigan
state: Michigan
city: Brooklyn
country: United States
facility: NY Scientific
state: New York
city: North Massapequa
country: United States
facility: DiGiovanna Institute for Medical Education & Research
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Gastroenterology & Hepatology P.L.L.C
state: North Carolina
city: Oklahoma City
country: United States
facility: DDSI
state: Oklahoma
city: Oklahoma City
country: United States
facility: Central Sooner Research
state: Oklahoma
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Omni Clinical Research
state: Texas
city: League City
country: United States
facility: UTMB Health
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: McGuire Research Institute
state: Virginia
city: Suffolk
country: United States
facility: IACT Health
state: Virginia
city: Milwaukee
country: United States
facility: Advocate Aurora Health - Aurora St. Luke's Medical Center
state: Wisconsin
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Military Area General Hospital/Seventh Medical Center of PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Tsinghua University Changgung Hospital
state: Beijing
city: Chongqing
country: China
facility: Army Medical Center of PLA
state: Chongqing
city: Chongqing
country: China
facility: Chongqing People's Hospital
state: Chongqing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospitial of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: Third Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technoloy
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: The Second Affiliated Hospital of Zhengzhou University
state: Hena
city: Jingzhou
country: China
facility: Jingzhou First People's Hospital
state: Hubei
city: Shiyan
country: China
facility: Affiliated Taihe Hospital of Hubei University of Medicine
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Zhuzhou
country: China
facility: Zhuzhou Central Hospital
state: Hunan
city: Baotou
country: China
facility: Baotou Central Hospital
state: Inner Mongolia
city: Huai'an
country: China
facility: Huai'an First People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing General Hospital of Nanjing Military Command
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Yangzhou
country: China
facility: Subei People's Hospital of Jiangsu province
state: Jiangsu
city: Shenyang
country: China
facility: Shengjing Hospital Of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Binzhou
country: China
facility: Binzhou Medical University Hospital
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Longhua Hospital Shanghai University of Traditional Chinese Medicine
state: Shanghai
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Changhai Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
state: Shanghai
city: Shanxi
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin medical University General Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Union Medical Center
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Jinhua
country: China
facility: Jinhua Municipal Central Hospical
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo First Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Tbilisi
country: Georgia
facility: Curatio, Jsc
city: Tbilisi
country: Georgia
facility: JSC Infectious Diseases, AIDS and Clinical Immunology Research Center
city: Tbilisi
country: Georgia
facility: LTD Central University Clinic After Academic N. Kipshidze
city: Tbilisi
country: Georgia
facility: LTD The First Medical Center
city: Bydgoszcz
country: Poland
facility: CLINSANTE Clinical Research Centre Ewa Galczak-Nowak, Malgorzata Trzaska
city: Knurow
country: Poland
facility: MZ BADANIA Slowik Zymla General Partnership
city: Krakow
country: Poland
facility: "Landa" Specialist Doctor's Offices
city: Krakow
country: Poland
facility: PLEJADY Medical Centre
city: Lodz
country: Poland
facility: AMED Medical Centre Branch in Lodz
city: Oswiecim
country: Poland
facility: Oswiecim Clinical Trial Centre
city: Poznan
country: Poland
facility: Private Healthcare Institution Specialist Clinics Termedica
city: Sopot
country: Poland
facility: Dariusz Kleczkowski Specialist Medical Practice
city: Torun
country: Poland
facility: Torun Gastrology Centre "Gastromed"
city: Warsaw
country: Poland
facility: MDM Healthcare Centre
city: Warsaw
country: Poland
facility: WIP Warsaw IBD Point
city: Wroclaw
country: Poland
facility: Medical Centre Oporow
city: Zamosc
country: Poland
facility: ETG Zamosc
city: Cherkasy
country: Ukraine
facility: Communal Nonprofit Enterprise "Cherkasy Regional Hospital of Cherkasy Oblast Council"
city: Chernivtsi
country: Ukraine
facility: Regional Municipal Non-commercial Enterprise "Chernivtsi Emergency Medical Hospital"
city: Ivano-Frankivsk
country: Ukraine
facility: Public Non-Profit Enterprise "Regional Clinical Hospital under Ivano-Frankivsk Regional Council"
city: Kharkiv
country: Ukraine
facility: Public Non-Profit Institution: O.O. Shalimov City Clinical Hospital #2 under Kharkiv City Council
city: Khmelnytskyi
country: Ukraine
facility: Public Non-Profit Enterprise "Khmelnytskyi Regional Hospital" under Khmelnytskyi Regional Council
city: Kyiv
country: Ukraine
facility: Clinical Hospital "Feofaniia"
city: Kyiv
country: Ukraine
facility: Medical Center "Consylium Medical"
city: Kyiv
country: Ukraine
facility: Medical Center OK!Clinic+ of the Company with Limited Liability International Institute of Clinical Research
city: Lutsk
country: Ukraine
facility: Municipal Enterprise "Volyn Regional Clinical Hospital" of Volyn Regional Council
city: Lviv
country: Ukraine
facility: Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital"
city: Sumy
country: Ukraine
facility: Public Non-Profit Enterprise under Sumy Regional Council "Sumy Regional Clinical Hospital"
city: Vinnytsia
country: Ukraine
facility: Communal Non-Commercial Enterprise: Vinnytsia City Clinical Hospital #1
city: Zaporizhia
country: Ukraine
facility: Public Non-Profit Enterprise "City Hospital #6" under Zaporizhia City Council
city: Zhytomyr
country: Ukraine
facility: "Medibor Plus" Llc
Study officials:
affiliation: Reistone Pharma
name: Xiang Chen
role: STUDY_DIRECTOR
References: