A Phase II Study in Patients With Moderate to Severe Active Ulcerative Colitis.
- Registration Number
- NCT03675477
- Lead Sponsor
- Reistone Biopharma Company Limited
- Brief Summary
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 Early withdrawn subjects during the first treatment phase can not enter the extension phase.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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 164
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo 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 SHR0302 8mg QD SHR0302 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). SHR0302 4mg BD SHR0302 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). SHR0302 4mg QD SHR0302 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). placebo SHR0302 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
- Primary Outcome Measures
Name Time Method The Percentage of Subject Achieve Clinical Response at Week 8 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. = 1-2 stools/day more than normal
2. = 3-4 stools/day more than normal
3. = 5 or more stools/day than normal
Rectal bleeding 0 = None
1. = Visible blood with stool less than half the time
2. = Visible blood with stool half of the time or more
3. = Passing blood alone
Mucosal appearance at endoscopy 0 = Normal or inactive disease
1. = Mild disease (erythema, decreased vascular pattern, mild friability
2. = Moderate disease (marked erythema, absent vascular pattern, friability, erosio
- Secondary Outcome Measures
Name Time Method The Percentage of Subjects Achieve Clinical Remission 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 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. = 1-2 stools/day more than normal
2. = 3-4 stools/day more than normal
3. = 5 or more stools/day than normal
Rectal bleeding 0 = None
1. = Visible blood with stool less than half the time
2. = Visible blood with stool half of the time or more
3. = Passing blood alone
Mucosal appearance at endoscopy 0 = Normal or inactive disease
1. = Mild disease (erythema, decreased vascular pattern, mild friability
2. = Moderate disease (marked erythema, absent vascular pattern, friability, erosions)
3. = Severe disease (spontaneous bleeding, ulceration)The Percentage of Subjects Achieve Clinical Remission at Week 8 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. = 1-2 stools/day more than normal
2. = 3-4 stools/day more than normal
3. = 5 or more stools/day than normal
Rectal bleeding 0 = None
1. = Visible blood with stool less than half the time
2. = Visible blood with stool half of the time or more
3. = Passing blood alone
Mucosal appearance at endoscopy 0 = Normal or inactive disease
1. = Mild disease (erythema, decreased vascular pattern, mild friability
2. = Moderate disease (marked erythema, absent vascular pattThe Percentage of Subjects Achieve Endoscopic Remission (Mucosal Healing) at Week 8 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).
Trial Locations
- Locations (66)
Wellness Clinical Research, LLLC-Central Florida
🇺🇸Lake Wales, Florida, United States
Central City Clinical Hospital Dept of Theraphy No. 2 SHEI Ivano-Frankivsk NMU
🇺🇦Ivano-Frankivs'k, Ukraine
Nzoz Formed
🇵🇱Wadowice, Poland
Twoja Przychodnia-Szczecinskie Centrum Medyczne
🇵🇱Szczecin, Poland
IP Clinic
🇵🇱Łódź, Poland
Digestive Disease Specialists, Inc.
🇺🇸Oklahoma City, Oklahoma, United States
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Peking University Shougang Hospital
🇨🇳Beijing, China
The First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, China
The First Hospital of Jillin University
🇨🇳Changchun, China
Xiangya Hospital Central South University
🇨🇳Changsha, China
The First People's Hospital of Lianyungang
🇨🇳Lianyungang, China
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, China
Renji Hospital, Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, China
The First Hospital of China Medical University
🇨🇳Shenyang, China
Second Hospital of Shanxi Medical University
🇨🇳Taiyuan, China
Tianjin Union Medical Center
🇨🇳Tianjin, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, China
Renmin Hospital of Wuhan University
🇨🇳Wuhan, China
Yijishan Hospital of Wannan Medical College
🇨🇳Wuhu, China
Baotou Central Hospital
🇨🇳Baotou, Inner Mongalia, China
Henan Provincial People's Hospital
🇨🇳Zhengzhou, Henan, China
West Central Gastroenterology d/b/a Gastro Florida
🇺🇸Tampa, Florida, United States
Liaocheng People's Hospital
🇨🇳Liaocheng, Shandong, China
Peking University Third Hospital
🇨🇳Beijing, China
West China Hospital Sichuan University
🇨🇳Chengdu, China
Fujian Provincial Hospital
🇨🇳Fuzhou, China
Huaian First People's Hospital
🇨🇳Huai'an, China
Huzhou Central Hospital
🇨🇳Huzhou, China
Sir Run Run Shaw Hospital
🇨🇳Hangzhou, China
The Sixth Affiliated Hospital of Sun Yat- Sen University
🇨🇳Guangzhou, China
Qilu Hospital of Shandong University
🇨🇳Jinan, China
Zhongda Hospital Southeast University
🇨🇳Nanjing, China
Shanghai East Hospital
🇨🇳Shanghai, China
Pingxiang People's Hospital
🇨🇳Pingxiang, China
Shanxi Provincial People's Hospital
🇨🇳Taiyuan, China
The University of Hong Kong - Shenzhen Hospital
🇨🇳Shenzhen, China
Tongji Hospital Affiliated to Tongji Medicine College
🇨🇳Wuhan, China
Amicare Sp. z o.o. Sp.k
🇵🇱Łódź, Poland
NZOZ Almedica
🇵🇱Nowy Targ, Poland
Indywidualma Specjalistyczna Praktyka Lekarska Maciej Zymla
🇵🇱Knurów, Poland
Specjalistyczna Praktyka Lekarska dr med. Marek Horynski
🇵🇱Sopot, Poland
PlanetMed sp. z o.o.
🇵🇱Wrocław, Poland
Nzoz Vivamed
🇵🇱Warszawa, Poland
Wellness Clinical Research, LLC
🇵🇷Vega Baja, Puerto Rico
I.I.Mechnykov Dnipropetrovsk Regional Clinical Hospital
🇺🇦Dnipro, Ukraine
Ivana -Frankivsk Hospital
🇺🇦Ivano-Frankivs'k, Ukraine
Kherson City Clinical Hospital
🇺🇦Kherson, Ukraine
Kyiv City Clinical Hospital #1
🇺🇦Kyiv, Ukraine
KO-MED Centra Kliniczne Staszow
🇵🇱Staszów, Poland
SOLUMED Centrum Medyczne
🇵🇱Poznań, Poland
KO-MED Centra Kliniczne Plulawy
🇵🇱Puławy, Poland
CHI Kharkiv City Clinical Hospital #13
🇺🇦Kharkiv, Ukraine
Khmelnytska Regional Hospital
🇺🇦Khmelnytskyi, Ukraine
CNE of Lviv Regional Council Lviv Regional Clinical Hospital
🇺🇦Lviv, Ukraine
Vinnytsia M.I.Pyrogov Regional Clinical Hospital
🇺🇦Vinnytsia, Ukraine
CCH #1 Vinnytsia M.I. Pyrogov NMU Ch of Propaedeutics of IM
🇺🇦Vinnytsia, Ukraine
RCI Chernivtsi Regional Clinical Hospital Dept of Gastroenterology Bukovinsky SMU
🇺🇦Chernivtsi, Ukraine
CI City Clinical Hospital #6 Dept of Gastroenterology
🇺🇦Zaporizhzhia, Ukraine
O.F. Herbachevskiyi Zhytomyr Regional Clinical Hospital
🇺🇦Zhytomyr, Ukraine
CI Karabelesh Kherson CCH
🇺🇦Kherson, Ukraine
Kyiv Railway Clinical Hospital #2 of Branch "Health Center" of the Public Joint Stock Company "Ukrai
🇺🇦Kyiv, Ukraine
Jiangsu Province Hospital
🇨🇳Nanjing, China
Nanjing First Hospital
🇨🇳Nanjing, China
Nanjing Drum Tower Hospital
🇨🇳Nanjing, China