A Phase II Study in Patients With Moderate to Severe Active Ulcerative Colitis.
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| ClinicalTrials.gov Identifier: NCT03675477 |
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Recruitment Status :
Completed
First Posted : September 18, 2018
Results First Posted : November 22, 2022
Last Update Posted : March 16, 2023
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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 Early withdrawn subjects during the first treatment phase can not enter the extension phase.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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ulcerative Colitis | Drug: SHR0302 Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 164 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | 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. |
| Actual Study Start Date : | April 13, 2019 |
| Actual Primary Completion Date : | November 30, 2020 |
| Actual Study Completion Date : | February 3, 2021 |
| Arm | Intervention/treatment |
|---|---|
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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 Name: Ivarmacitinib |
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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 Name: 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 Name: Ivarmacitinib |
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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: SHR0302
The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a Janus kinase inhibitor).
Other Name: Ivarmacitinib Drug: Placebo Placebo Oral Tablet |
- The Percentage of Subject Achieve Clinical Response at Week 8 [ Time Frame: 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
- The Percentage of Subjects Achieve Clinical Remission [ Time Frame: 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
- = 1-2 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)
- The Percentage of Subjects Achieve Clinical Remission at Week 8 [ Time Frame: 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
- The Percentage of Subjects Achieve Endoscopic Remission (Mucosal Healing) at Week 8 [ Time Frame: 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).
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03675477
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| Study Director: | Xiang Chen | Reistone Pharma |
Documents provided by Reistone Biopharma Company Limited:
| Responsible Party: | Reistone Biopharma Company Limited |
| ClinicalTrials.gov Identifier: | NCT03675477 |
| Other Study ID Numbers: |
RSJ10101 2018-003364-31 ( EudraCT Number ) |
| First Posted: | September 18, 2018 Key Record Dates |
| Results First Posted: | November 22, 2022 |
| Last Update Posted: | March 16, 2023 |
| Last Verified: | December 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Colitis Colitis, Ulcerative Ulcer Gastroenteritis Gastrointestinal Diseases |
Digestive System Diseases Colonic Diseases Intestinal Diseases Pathologic Processes Inflammatory Bowel Diseases |