A Phase II Study in Patients With Moderate to Severe Active Ulcerative Colitis.

A Phase II Randomized, Placebo Controlled, Double-blind, 4 Arms Dose-ranging Study to Evaluate the Efficacy and Safety of SHR0302 Compared to Placebo in Patients With Moderate to Severe Active Ulcerative Colitis.

The proposed study is a randomized, double-blind,placebo-controlled, multicenter phase II study to investigate the safety and efficacy of SHR0302 in patients with moderate to severe active ulcerative colitis. The study aims to evaluate the optimal dose of SHR0302 and time needed to induce clinical response in active ulcerative colitis patients.

This is an 8+8 weeks study, in which participants who complete the first 8 weeks treatment phase, will have the option to enter a blinded active arms 8-week extension phase. Early withdrawn subjects during the first treatment phase can not enter the extension phase. The total duration of the study participation, including extension and follow-up, will be approximately 18 weeks.

SHR0302 is a Janus kinase 1(JAK1) inhibitor, capable of blocking Janus kinase-signal transducer and activator of transcription (JAK-STATs) pathway and controlling inflammation. Therefore it has the potential to be a treatment for ulcerative colitis.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Placebo; Drug: SHR0302

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100041
    • Peking University Shougang Hospital
  • Bengbu, China, 233004
    • The First Affiliated Hospital of Bengbu Medical College
  • Changchun, China, 130021
    • The First Hospital of Jillin University
  • Changsha, China, 410008
    • Xiangya Hospital Central South University
  • Chengdu, China, 610041
    • West China Hospital Sichuan University
  • Fuzhou, China, 350001
    • Fujian Provincial Hospital
  • Guangzhou, China, 510655
    • The Sixth Affiliated Hospital of Sun Yat- Sen University
  • Hangzhou, China, 310016
    • Sir Run Run Shaw Hospital
  • Huai'an, China, 223300
    • Huaian First People's Hospital
  • Huzhou, China, 313000
    • Huzhou Central Hospital
  • Jinan, China, 250012
    • Qilu Hospital of Shandong University
  • Lianyungang, China, 222061
    • The First People's Hospital of Lianyungang
  • Nanjing, China, 210006
    • Jiangsu Province Hospital
  • Nanjing, China, 210008
    • Nanjing Drum Tower Hospital
  • Nanjing, China, 210006
    • Nanjing First Hospital
  • Nanjing, China, 210009
    • Zhongda Hospital Southeast University
  • Pingxiang, China, 337000
    • Pingxiang People's Hospital
  • Shanghai, China, 200025
    • Ruijin Hospital, Shanghai JiaoTong University School of Medicine
  • Shanghai, China, 200000
    • Shanghai East Hospital
  • Shanghai, China, 200127
    • Renji Hospital, Shanghai Jiaotong University School of Medicine
  • Shenyang, China, 110001
    • The First Hospital of China Medical University
  • Shenzhen, China, 518000
    • The University of Hong Kong - Shenzhen Hospital
  • Taiyuan, China, 030001
    • Shanxi Provincial People's Hospital
  • Taiyuan, China, 030012
    • Second Hospital of Shanxi Medical University
  • Tianjin, China, 300000
    • Tianjin Union Medical Center
  • Wenzhou, China, 325000
    • The First Affiliated Hospital of Wenzhou Medical University
  • Wuhan, China, 430060
    • Renmin Hospital of Wuhan University
  • Wuhan, China, 430030
    • Tongji Hospital Affiliated to Tongji Medicine College
  • Wuhu, China, 241001
    • Yijishan Hospital of Wannan Medical College
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510000
      • Guangdong Provincial People's Hospital
  • Henan
    • Zhengzhou, Henan, China, 453000
      • Henan Provincial People's Hospital
  • Inner Mongalia
    • Baotou, Inner Mongalia, China, 014040
      • Baotou Central Hospital
  • Shandong
    • Liaocheng, Shandong, China, 252000
      • Liaocheng People's Hospital
• Poland
  • Knurów, Poland, 44-190
    • Indywidualma Specjalistyczna Praktyka Lekarska Maciej Zymla
  • Nowy Targ, Poland, 34400
    • NZOZ Almedica
  • Poznań, Poland, 60-529
    • Solumed Centrum Medyczne
  • Puławy, Poland, 24-100
    • KO-MED Centra Kliniczne Plulawy
  • Sopot, Poland, 81-756
    • Specjalistyczna Praktyka Lekarska dr med. Marek Horynski
  • Staszów, Poland, 28-200
    • KO-MED Centra Kliniczne Staszow
  • Szczecin, Poland, 71434
    • Twoja Przychodnia-Szczecinskie Centrum Medyczne
  • Wadowice, Poland, 01868
    • NZOZ Formed
  • Wadowice, Poland, 34100
    • NZOZ Formed
  • Warszawa, Poland, 03-580
    • NZOZ Vivamed
  • Wrocław, Poland, 53-333
    • PlanetMed sp. z o.o.
  • Łódź, Poland, 90-644
    • AMICARE Sp. z o.o. sp.k
  • Łódź, Poland, 90752
    • IP Clinic
• Puerto Rico
  • Vega Baja, Puerto Rico, 00694
    • Wellness Clinical Research, LLC
• Ukraine
  • Chernivtsi, Ukraine, 58002
    • RCI Chernivtsi Regional Clinical Hospital Dept of Gastroenterology Bukovinsky SMU
  • Dnipro, Ukraine, 49005
    • I.I.Mechnykov Dnipropetrovsk Regional Clinical Hospital
  • Ivano-Frankivs'k, Ukraine, 76018
    • Central City Clinical Hospital Dept of Theraphy No. 2 SHEI Ivano-Frankivsk NMU
  • Ivano-Frankivs'k, Ukraine, 76018
    • Ivana -Frankivsk Hospital
  • Kharkiv, Ukraine, 61124
    • CHI Kharkiv City Clinical Hospital #13
  • Kherson, Ukraine, 73000
    • CI Karabelesh Kherson CCH
  • Kherson, Ukraine, 73000
    • Kherson City Clinical Hospital
  • Khmelnytskyi, Ukraine, 29000
    • Khmelnytska Regional Hospital
  • Kyiv, Ukraine, 02091
    • Kyiv City Clinical Hospital #1
  • Kyiv, Ukraine, 03049
    • Kyiv Railway Clinical Hospital #2 of Branch "Health Center" of the Public Joint Stock Company "Ukrai
  • Lviv, Ukraine, 79010
    • CNE of Lviv Regional Council Lviv Regional Clinical Hospital
  • Vinnytsia, Ukraine, 21029
    • CCH #1 Vinnytsia M.I. Pyrogov NMU Ch of Propaedeutics of IM
  • Vinnytsia, Ukraine, 21018
    • Vinnytsia M.I.Pyrogov Regional Clinical Hospital
  • Zaporizhzhia, Ukraine, 69035
    • CI City Clinical Hospital #6 Dept of Gastroenterology
  • Zhytomyr, Ukraine, 10002
    • O.F. Herbachevskiyi Zhytomyr Regional Clinical Hospital
• United States
  • Florida
    • Lake Wales, Florida, United States, 33853
      • Wellness Clinical Research, LLLC-Central Florida
    • Tampa, Florida, United States, 33626
      • West Central Gastroenterology d/b/a Gastro Florida
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Digestive Disease Specialists, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and Female subject age ≥ 18 and ≤75 years of age at randomization.
• Active ulcerative colitis with a 9-point modified Mayo score of 5 to 9 points and endoscopic subscore of 2 to 3 (The duration of the time between endoscopy and baseline should not exceed 10 days and allow central over read turn over before randomization).
• Subject should have at least three-month history of Ulcerative Colitis diagnosis at randomization.

Exclusion Criteria:

• Diagnosis of indeterminate colitis, or clinical findings suggestive of Crohn's disease.
• Subjects with ulcerative colitis, which is confined to a proctitis (distal 15 cm or less).
• Treatment naïve subjects diagnosed with ulcerative colitis (without previous exposure to treatment).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR0302 8mg QD; Participants randomized in this arm will receive SHR0302 8mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 8mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Drug: SHR0302; The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a Janus kinase inhibitor).; Other Names: Ivarmacitinib
Experimental: SHR0302 4mg BD; Participants randomized in this arm will receive SHR0302 4mg BD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg BD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Drug: SHR0302; The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a Janus kinase inhibitor).; Other Names: Ivarmacitinib
Experimental: SHR0302 4mg QD; Participants randomized in this arm will receive SHR0302 4mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Drug: SHR0302; The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a Janus kinase inhibitor).; Other Names: Ivarmacitinib
Placebo Comparator: placebo; Participants randomized in this arm will receive the placebo until week 8, and then will be re-randomized into one of the 3 active arms ( 4mg QD, 4mg BD, 8mg QD of SHR0302) in a 1:1:1 allocation ratio until the end of the study at week 16. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor). Placebos: Placebo Oral Tablet	Drug: Placebo; Placebo Oral Tablet; Drug: SHR0302; The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a Janus kinase inhibitor).; Other Names: Ivarmacitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Subject Achieve Clinical Response at Week 8	Clinical response is defined as a decrease from baseline in a 9-point modified Mayo score of at least 2 points and at least 30%, with an accompanying reduction in the subscore for rectal bleeding of at least 1 point or absolute subscore for rectal bleeding of 0 or 1. The 9-point modified Mayo score is the Mayo score excluding the Physician Global Assessment sub-score, hence the maximum is 9 points and the minimum is 0 point, includes: Stool Frequency 0 = Normal; = 1-2 stools/day more than normal; = 3-4 stools/day more than normal; = 5 or more stools/day than normal Rectal bleeding 0 = None; = Visible blood with stool less than half the time; = Visible blood with stool half of the time or more; = Passing blood alone Mucosal appearance at endoscopy 0 = Normal or inactive disease; = Mild disease (erythema, decreased vascular pattern, mild friability; = Moderate disease (marked erythema, absent vascular pattern, friability, erosio	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Subjects Achieve Clinical Remission	Clinical remission was defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point. The percentage of subjects who achieve clinical remission per 9-point modified Mayo score at week 8, where stool frequency subscore ≤ 1, rectal bleeding subscore of 0, and endoscopic subscore ≤ 1. 9-point modified Mayo score includes: Stool Frequency 0 = Normal; = 1-2 stools/day more than normal; = 3-4 stools/day more than normal; = 5 or more stools/day than normal Rectal bleeding 0 = None; = Visible blood with stool less than half the time; = Visible blood with stool half of the time or more; = Passing blood alone Mucosal appearance at endoscopy 0 = Normal or inactive disease; = Mild disease (erythema, decreased vascular pattern, mild friability; = Moderate disease (marked erythema, absent vascular pattern, friability, erosions); = Severe disease (spontaneous bleeding, ulceration)	Week 8
The Percentage of Subjects Achieve Clinical Remission at Week 8	Clinical remission was defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point. The percentage of subjects achieve clinical remission at week 8 as per a total Mayo score of 2 points or lower ≤2, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. The 9-point modified Mayo score includes: Stool Frequency 0 = Normal; = 1-2 stools/day more than normal; = 3-4 stools/day more than normal; = 5 or more stools/day than normal Rectal bleeding 0 = None; = Visible blood with stool less than half the time; = Visible blood with stool half of the time or more; = Passing blood alone Mucosal appearance at endoscopy 0 = Normal or inactive disease; = Mild disease (erythema, decreased vascular pattern, mild friability; = Moderate disease (marked erythema, absent vascular patt	Week 8
The Percentage of Subjects Achieve Endoscopic Remission (Mucosal Healing) at Week 8	Endoscopic remission was defined by Mayo endoscopic subscore ≤ 1 point. Mayo endoscopic subscore defines score 0 as normal or inactive disease, score 1 as mild disease (erythema, decreased vascular pattern, mild friability); score 2 as moderate disease (marked erythema, absent vascular pattern, friability, erosions)； score 3 as severe disease (spontaneous bleeding, ulceration).	Week 8

Collaborators and Investigators

• Sponsor: Reistone Biopharma Company Limited
• Investigators: Study Director: Xiang Chen, Reistone Pharma

Publications and helpful links

General Publications

• Chen B, Zhong J, Li X, Pan F, Ding Y, Zhang Y, Chen H, Liu F, Zhang Z, Zhang L, Drozda R, Oliinyk O, Goh AH, Chen X, Sun X, Rubin DT, Sandborn WJ, Chen M. Efficacy and Safety of Ivarmacitinib in Patients With Moderate-to-Severe, Active, Ulcerative Colitis: A Phase II Study. Gastroenterology. 2022 Dec;163(6):1555-1568. doi: 10.1053/j.gastro.2022.08.007. Epub 2022 Aug 10.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2019
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): February 3, 2021

Study Registration Dates

• First Submitted: September 16, 2018
• First Submitted That Met QC Criteria: September 16, 2018
• First Posted (Actual): September 18, 2018

Study Record Updates

• Last Update Posted (Actual): June 2, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: RSJ10101; 2018-003364-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No