A Phase 3 Study to Investigate the Efficacy and Safety of SHR0302 With Moderately to Severely Active Ulcerative Colitis

Ulcerative Colitis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05181137
• Other study ID #: RSJ10135
• Status: Recruiting
• Phase: Phase 3
• Start date: November 5, 2021
• Est. completion date: March 31, 2025

Study information

• Verified date: September 2023
• Source: Reistone Biopharma Company Limited
• Contact: Minna Sun
• Phone: +86 18611785877
• Email: minna.sun[@]reistonebio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 368
• Est. completion date: March 31, 2025
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• SHR0302
Oral tablets taken once daily (QD)
• Placebo
Oral tablets taken once daily (QD)

Locations

Country	Name	City	State
China	Baotou Central Hospital	Baotou	Inner Mongolia
China	Beijing Military Area General Hospital/Seventh Medical Center of PLA General Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	Tsinghua University Changgung Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Binzhou Medical University Hospital	Binzhou	Shandong
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	Xiangya Hospital Central South University	Changsha	Hunan
China	West China Hospital Sichuan University	Chengdu	Sichuan
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 First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The Sixth Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong
China	Third Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	Huai'an First People's Hospital	Huai'an	Jiangsu
China	Jingzhou First People's Hospital	Jingzhou	Hubei
China	Jinhua Municipal Central Hospical	Jinhua	Zhejiang
China	Liaocheng People's Hospital	Liaocheng	Shandong
China	The First Affiliated Hospital of Henan University of Science and Technoloy	Luoyang	Henan
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Nanjing First Hospital	Nanjing	Jiangsu
China	Nanjing General Hospital of Nanjing Military Command	Nanjing	Jiangsu
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Ningbo First Hospital	Ningbo	Zhejiang
China	Huashan Hospital, Fudan University	Shanghai	Shanghai
China	Longhua Hospital Shanghai University of Traditional Chinese Medicine	Shanghai	Shanghai
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	Zhongshan Hospital Affiliated to Fudan University	Shanghai	Shanghai
China	Shanxi Provincial People's Hospital	Shanxi	Shanxi
China	Shengjing Hospital Of China Medical University	Shenyang	Liaoning
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Affiliated Taihe Hospital of Hubei University of Medicine	Shiyan	Hubei
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	The First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Tianjin medical University General Hospital	Tianjin	Tianjin
China	Tianjin Union Medical Center	Tianjin	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Renmin Hospital of Wuhan University	Wuhan	Hubei
China	The First Affiliated Hospitial of Xiamen University	Xiamen	Fujian
China	Subei People's Hospital of Jiangsu province	Yangzhou	Jiangsu
China	Henan Provincial People's Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	The Second Affiliated Hospital of Zhengzhou University	Zhengzhou	Hena
China	Zhuzhou Central Hospital	Zhuzhou	Hunan
Georgia	Curatio, Jsc	Tbilisi
Georgia	JSC Infectious Diseases, AIDS and Clinical Immunology Research Center	Tbilisi
Georgia	LTD Central University Clinic After Academic N. Kipshidze	Tbilisi
Georgia	LTD The First Medical Center	Tbilisi
Poland	CLINSANTE Clinical Research Centre Ewa Galczak-Nowak, Malgorzata Trzaska	Bydgoszcz
Poland	MZ BADANIA Slowik Zymla General Partnership	Knurow
Poland	"Landa" Specialist Doctor's Offices	Krakow
Poland	PLEJADY Medical Centre	Krakow
Poland	AMED Medical Centre Branch in Lodz	Lodz
Poland	Oswiecim Clinical Trial Centre	Oswiecim
Poland	Private Healthcare Institution Specialist Clinics Termedica	Poznan
Poland	Dariusz Kleczkowski Specialist Medical Practice	Sopot
Poland	Torun Gastrology Centre "Gastromed"	Torun
Poland	MDM Healthcare Centre	Warsaw
Poland	WIP Warsaw IBD Point	Warsaw
Poland	Medical Centre Oporow	Wroclaw
Poland	ETG Zamosc	Zamosc
Ukraine	Communal Nonprofit Enterprise "Cherkasy Regional Hospital of Cherkasy Oblast Council"	Cherkasy
Ukraine	Regional Municipal Non-commercial Enterprise "Chernivtsi Emergency Medical Hospital"	Chernivtsi
Ukraine	Public Non-Profit Enterprise "Regional Clinical Hospital under Ivano-Frankivsk Regional Council"	Ivano-Frankivsk
Ukraine	Public Non-Profit Institution: O.O. Shalimov City Clinical Hospital #2 under Kharkiv City Council	Kharkiv
Ukraine	Public Non-Profit Enterprise "Khmelnytskyi Regional Hospital" under Khmelnytskyi Regional Council	Khmelnytskyi
Ukraine	Clinical Hospital "Feofaniia"	Kyiv
Ukraine	Medical Center "Consylium Medical"	Kyiv
Ukraine	Medical Center OK!Clinic+ of the Company with Limited Liability International Institute of Clinical Research	Kyiv
Ukraine	Municipal Enterprise "Volyn Regional Clinical Hospital" of Volyn Regional Council	Lutsk
Ukraine	Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital"	Lviv
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	Public Non-Profit Enterprise "City Hospital #6" under Zaporizhia City Council	Zaporizhia
Ukraine	"Medibor Plus" Llc	Zhytomyr
United States	Michigan Medical	Ann Arbor	Michigan
United States	NY Scientific	Brooklyn	New York
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	Research Institute of Michigan	Chesterfield	Michigan
United States	John Hopkins University	Columbia	Maryland
United States	Digestive Health Specialists	Dothan	Alabama
United States	Omni Clinical Research	Houston	Texas
United States	IHS Health	Kissimmee	Florida
United States	Om Research LLC	Lancaster	California
United States	UTMB Health	League City	Texas
United States	Dade Research Center	Miami	Florida
United States	Advocate Aurora Health - Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	One Health Research Clinic Atlanta, LLC	Norcross	Georgia
United States	DiGiovanna Institute for Medical Education & Research	North Massapequa	New York
United States	Central Sooner Research	Oklahoma City	Oklahoma
United States	DDSI	Oklahoma City	Oklahoma
United States	Gastro Florida	Pinellas Park	Florida
United States	McGuire Research Institute	Richmond	Virginia
United States	University of Utah	Salt Lake City	Utah
United States	IACT Health	Suffolk	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Reistone Biopharma Company Limited

Countries where clinical trial is conducted

United States,  China,  Georgia,  Poland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical remission at week 8 (Part 1)	The percentage of subjects in clinical remission at week 8.	8 weeks
Primary	Clinical remission at week 52 (Part 2)	The percentage of subjects in clinical remission at week 52.	52 weeks
Secondary	Endoscopic remission at week 8 (Part 1)	The percentage of subjects with endoscopic remission at week 8.	8 weeks
Secondary	Clinical response at week 8 (Part 1)	The percentage of subjects with clinical response at week 8.	8 weeks
Secondary	Change from baseline in partial Mayo score at week 2, 4, and 8 (Part 1)	Change from baseline in partial Mayo score at week 2, 4, and 8.	8 weeks
Secondary	Change in total Mayo score and 9-point modified Mayo score at week 8 (Part 1)	Change in total Mayo score and 9-point modified Mayo score at week 8.	8 weeks
Secondary	Subjects with endoscopic remission (Part 2)	The percentage of subjects with endoscopic remission at week 52.	52 weeks
Secondary	Subjects with clinical response at week 52 (Part 2)	The percentage of subjects with clinical response at week 52.	52 weeks
Secondary	Change from baseline in partial Mayo score at week 12, 16, 24, 32, 40, and 52 (Part 2)	Change from baseline in partial Mayo score at week 12, 16, 24, 32, 40, and 52.	52 weeks
Secondary	Change in total Mayo score and 9-point modified Mayo score at week 52 (Part 2)	Change in total Mayo score and 9-point modified Mayo score at week 52.	52 weeks
Secondary	Subjects in corticosteroid-free remission at week 52 (Part 2)	Percentage of subjects in corticosteroid-free remission at week 52.	52 weeks
Secondary	Subjects who maintain clinical remission at week 52 (Part 2)	Percentage of subjects who maintain clinical remission at week 52	52 weeks
Secondary	Subjects in clinical remission per partial Mayo score at week E26 (Part 3)	The percentage of subjects in clinical remission per partial Mayo score at week E26.	26 weeks (extension)
Secondary	Subjects in corticosteroid-free remission per Partial Mayo score at week E26 (Part 3)	The percentage of subjects in corticosteroid-free remission per Partial Mayo score at week E26.	26 weeks (extension)
Secondary	Change from baseline in Partial Mayo score at week E2, E12, and E26 (Part 3)	Change from baseline in Partial Mayo score at week E2, E12, and E26.	26 weeks (extension)