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

Sponsor

Reistone Biopharma Company Limited (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05181137

Collaborator

(none)

368

Enrollment

109

Locations

Arms

40.8

Anticipated Duration (Months)

3.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: SHR0302 Drug: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

368 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 5, 2021

Anticipated Primary Completion Date :

Oct 31, 2024

Anticipated Study Completion Date :

Mar 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Active Experimental: SHR0302 Dose#1 SHR0302 Oral tablets taken once daily (QD) for 8 weeks SHR0302 Oral tablets taken once daily (QD)	Drug: SHR0302 Oral tablets taken once daily (QD)
Placebo Comparator: Part 1 Placebo Comparator: Placebo Placebo Oral tablets taken once daily (QD) for 8 weeks	Drug: Placebo Oral tablets taken once daily (QD)
Experimental: Part 2 Active Experimental: SHR0302 Dose#2 SHR0302 Oral tablets taken once daily (QD) for 44 weeks	Drug: SHR0302 Oral tablets taken once daily (QD)
Placebo Comparator: Part 2 Placebo Comparator: Placebo Placebo Comparator: Maintenance Treatment Placebo Comparator: Placebo	Drug: Placebo Oral tablets taken once daily (QD)
Experimental: Part 3 Active Experimental: SHR0302 Dose#2 SHR0302 Oral tablets taken once daily (QD) for 26 weeks	Drug: SHR0302 Oral tablets taken once daily (QD)

Outcome Measures

Primary Outcome Measures

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

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 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 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.
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 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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Digestive Health Specialists	Dothan	Alabama	United States	36301
2	Om Research LLC	Lancaster	California	United States	93534
3	Yale University	New Haven	Connecticut	United States	06510
4	IHS Health	Kissimmee	Florida	United States	34741
5	Dade Research Center	Miami	Florida	United States	33126
6	Gastro Florida	Pinellas Park	Florida	United States	33781
7	One Health Research Clinic Atlanta, LLC	Norcross	Georgia	United States	30039
8	John Hopkins University	Columbia	Maryland	United States	21045
9	Michigan Medical	Ann Arbor	Michigan	United States	48109
10	Research Institute of Michigan	Chesterfield	Michigan	United States	48047
11	NY Scientific	Brooklyn	New York	United States	11235
12	DiGiovanna Institute for Medical Education & Research	North Massapequa	New York	United States	11758
13	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
14	Charlotte Gastroenterology & Hepatology P.L.L.C	Charlotte	North Carolina	United States	28207
15	DDSI	Oklahoma City	Oklahoma	United States	73112
16	Central Sooner Research	Oklahoma City	Oklahoma	United States	73118
17	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37204
18	Omni Clinical Research	Houston	Texas	United States	77034
19	UTMB Health	League City	Texas	United States	77573
20	University of Utah	Salt Lake City	Utah	United States	84132
21	McGuire Research Institute	Richmond	Virginia	United States	23249
22	IACT Health	Suffolk	Virginia	United States	23435
23	Advocate Aurora Health - Aurora St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
24	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui	China
25	Anhui Provincial Hospital	Hefei	Anhui	China
26	Beijing Military Area General Hospital/Seventh Medical Center of PLA General Hospital	Beijing	Beijing	China
27	Peking University First Hospital	Beijing	Beijing	China
28	Peking University Third Hospital	Beijing	Beijing	China
29	Army Medical Center of PLA	Chongqing	Chongqing	China
30	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing	China
31	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian	China
32	The First Affiliated Hospitial of Xiamen University	Xiamen	Fujian	China
33	Guangzhou First People's Hospital	Guangzhou	Guangdong	China
34	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong	China
35	The Sixth Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong	China
36	Peking University Shenzhen Hospital	Shenzhen	Guangdong	China
37	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi	China
38	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei	China
39	The First Affiliated Hospital of Henan University of Science and Technoloy	Luoyang	Henan	China
40	Henan Provincial People's Hospital	Zhengzhou	Henan	China
41	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China
42	The Second Affiliated Hospital of Zhengzhou University	Zhengzhou	Hena	China
43	Affiliated Taihe Hospital of Hubei University of Medicine	Shiyan	Hubei	China
44	Renmin Hospital of Wuhan University	Wuhan	Hubei	China
45	The Second Xiangya Hospital of Central South University	Changsha	Hunan	China
46	Xiangya Hospital Central South University	Changsha	Hunan	China
47	Zhuzhou Central Hospital	Zhuzhou	Hunan	China
48	Baotou Central Hospital	Baotou	Inner Mongolia	China
49	Huai'an First People's Hospital	Huai'an	Jiangsu	China
50	Jiangsu Province Hospital	Nanjing	Jiangsu	China
51	Nanjing First Hospital	Nanjing	Jiangsu	China
52	Nanjing General Hospital of Nanjing Military Command	Nanjing	Jiangsu	China
53	Zhongda Hospital Southeast University	Nanjing	Jiangsu	China
54	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China
55	Subei People's Hospital of Jiangsu province	Yangzhou	Jiangsu	China
56	Shengjing Hospital Of China Medical University	Shenyang	Liaoning	China
57	The First Hospital of China Medical University	Shenyang	Liaoning	China
58	Liaocheng People's Hospital	Liaocheng	Shandong	China
59	Binzhou Medical University Hospital	Binzhou	Shandon	China
60	Huashan Hospital, Fudan University	Shanghai	Shanghai	China
61	Longhua Hospital Shanghai University of Traditional Chinese Medicine	Shanghai	Shanghai	China
62	Renji Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China
63	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China
64	Shanghai Changhai Hospital	Shanghai	Shanghai	China
65	Shanghai East Hospital	Shanghai	Shanghai	China
66	Shanghai General Hospital	Shanghai	Shanghai	China
67	Shanghai Sixth People's Hospital	Shanghai	Shanghai	China
68	Zhongshan Hospital Affiliated to Fudan University	Shanghai	Shanghai	China
69	Shanxi Provincial People's Hospital	Shanxi	Shanxi	China
70	The First Hospital of Shanxi Medical University	Taiyuan	Shanxi	China
71	West China Hospital Sichuan University	Chengdu	Sichuan	China
72	Tianjin medical University General Hospital	Tianjin	Tianjin	China
73	Tianjin Union Medical Center	Tianjin	Tianjin	China
74	The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine	Hangzhou	Zhejiang	China
75	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang	China
76	Jinhua Municipal Central Hospical	Jinhua	Zhejiang	China
77	Ningbo First Hospital	Ningbo	Zhejiang	China
78	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang	China
79	Curatio, Jsc	Tbilisi		Georgia
80	JSC Infectious Diseases, AIDS and Clinical Immunology Research Center	Tbilisi		Georgia
81	LTD Central University Clinic After Academic N. Kipshidze	Tbilisi		Georgia
82	LTD The First Medical Center	Tbilisi		Georgia
83	CLINSANTE Clinical Research Centre Ewa Galczak-Nowak, Malgorzata Trzaska	Bydgoszcz		Poland
84	Maciej Zymla Individual Medical Practice	Knurow		Poland
85	"Landa" Specialist Doctor's Offices	Krakow		Poland
86	PLEJADY Medical Centre	Krakow		Poland
87	AMED Medical Centre Branch in Lodz	Lodz		Poland
88	Oswiecim Clinical Trial Centre	Oswiecim		Poland
89	Medical Centre Grunwald	Poznan		Poland
90	Dariusz Kleczkowski Specialist Medical Practice	Sopot		Poland
91	Torun Gastrology Centre "Gastromed"	Torun		Poland
92	MDM Healthcare Centre	Warsaw		Poland
93	WIP Warsaw IBD Point	Warsaw		Poland
94	Medical Centre Oporow	Wroclaw		Poland
95	ETG Zamosc	Zamosc		Poland
96	Communal Nonprofit Enterprise "Cherkasy Regional Hospital of Cherkasy Oblast Council"	Cherkasy		Ukraine
97	Regional Municipal Non-commercial Enterprise "Chernivtsi Emergency Medical Hospital"	Chernivtsi		Ukraine
98	Public Non-Profit Enterprise "Regional Clinical Hospital under Ivano-Frankivsk Regional Council"	Ivano-Frankivsk		Ukraine
99	Public Non-Profit Institution: O.O. Shalimov City Clinical Hospital #2 under Kharkiv City Council	Kharkiv		Ukraine
100	Public Non-Profit Enterprise "Khmelnytskyi Regional Hospital" under Khmelnytskyi Regional Council	Khmelnytskyi		Ukraine
101	Clinical Hospital "Feofaniia"	Kyiv		Ukraine
102	Medical Center "Consylium Medical"	Kyiv		Ukraine
103	Medical Center OK!Clinic+ of the Company with Limited Liability International Institute of Clinical Research	Kyiv		Ukraine
104	Municipal Enterprise "Volyn Regional Clinical Hospital" of Volyn Regional Council	Lutsk		Ukraine
105	Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital"	Lviv		Ukraine
106	Public Non-Profit Enterprise under Sumy Regional Council "Sumy Regional Clinical Hospital"	Sumy		Ukraine
107	Communal Non-Commercial Enterprise: Vinnytsia City Clinical Hospital #1	Vinnytsia		Ukraine
108	Public Non-Profit Enterprise "City Hospital #6" under Zaporizhia City Council	Zaporizhia		Ukraine
109	"Medibor Plus" Llc	Zhytomyr		Ukraine

Sponsors and Collaborators

Reistone Biopharma Company Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Reistone Biopharma Company Limited

ClinicalTrials.gov Identifier:

NCT05181137

Other Study ID Numbers:

RSJ10135

First Posted:

Jan 6, 2022

Last Update Posted:

May 24, 2022

Last Verified:

Nov 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Colitis

Colitis, Ulcerative

Ulcer

Study Results

No Results Posted as of May 24, 2022