A Phase II Study in Patients With Moderate to Severe Active Crohn's Disease

Study Overview
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Brief Summary
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The proposed study is a randomized, double-blind, placebo-controlled, multi-center Phase II study to investigate the safety and efficacy of SHR0302 in patients with moderate to severe active Crohn's Disease. The study aims to evaluate the optimal dose of SHR0302 and time needed in inducing clinical remission in active CD. This is an 12+12 weeks study, in which participants who complete the first 12 weeks treatment phase, will have the option to enter a blinded active arms 12-week extension phase. Early withdrawn subjects during the first treatment phase cannot enter the extension phase. The total duration of the study participation, including extension and follow-up, will be approximately 26 weeks. With the wealth of scientific evidence on JAK/STAT involvement in IBD, the data from similar class of new drugs and the current data on SHR0302 (JAK1 inhibitor), support the rationale to proceed with phase II studies to evaluate the efficacy and safety of SHR0302 in patients with moderate to severe active CD.

Official Title
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A Phase II Randomized, Placebo Controlled, Double-blind, Four Arms Dose-ranging Study to Evaluate the Efficacy and Safety of SHR0302 Compared to Placebo in Patients With Moderate to Severe Active Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: SHR0302
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and Female subject at ≥18 and ≤ 75 years of age at randomization. Subjects with a documented three-month history of diagnosed ileal, colonic, or ileocolonic Crohn's Disease at the time of randomization. Currently having Crohn's Disease with Crohn's Disease Activity Index (CDAI) score ≥ 220 to ≤450. Exclusion Criteria: Diagnosis of indeterminate colitis, or clinical findings suggestive of Ulcerative Colitis. Subject with CD with stoma, gastric or ileoanal pouch, proto-colectomy or total colectomy, symptomatic stenosis or stricture, history of bowel perforation, suspected abscess; actively draining fistula. Treatment naïve subjects diagnosed with Crohn's disease, (without previous exposure to treatment).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SHR0302 dose A<br>Participants randomized in this arm will receive dose A of SHR0302 until end of study at week 24. | Drug: SHR0302<br>* The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).<br>|
| Experimental: SHR0302 dose B<br>Participants randomized in this arm will receive dose B of SHR0302 until end of study at week 24. | Drug: SHR0302<br>* The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).<br>|
| Experimental: SHR0302 dose C<br>Participants randomized in this arm will receive dose C of SHR0302 until end of study at week 24. | Drug: SHR0302<br>* The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).<br>|
| Placebo Comparator: Placebo<br>Participants randomized in this arm will receive placebo until week 12, and then will be re-randomized into one of the 3 active arms (dose A, dose B, and dose C of SHR0302) in a 1:1:1 allocation ratio until the end of study at week 24. | Drug: SHR0302<br>* The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).<br>Drug: Placebos<br>* Placebos<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of subjects achieving clinical remission at week 12. | The percentage of subjects achieving clinical remission at week 12, defined as Crohn's Disease Activity Index (CDAI) score < 150. | week12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of subjects achieving clinical remission defined as mean daily stool frequency (SF) ≤2.5, and abdominal pain (AP) ≤ 1 using the Patient Reported Outcome from CDAI at week 1, 4, 8, 12, 13, 16, and 24. | The percentage of subjects achieving clinical remission defined as mean daily stool frequency (SF) ≤2.5, and abdominal pain (AP) ≤ 1 using the Patient Reported Outcome from CDAI at week 1, 4, 8, 12, 13, 16, and 24. | week 1, 4, 8, 12, 13, 16, and 24 | 
| The percentage of subjects achieving clinical remission defined as PRO2 < 8 at week 1, 4, 8, 12, 13, 16, and 24. | The percentage of subjects achieving clinical remission defined as PRO2 < 8 at week 1, 4, 8, 12, 13, 16, and 24. | week 1, 4, 8, 12, 13, 16, and 24 | 
| The percentage of subjects achieving clinical response defined as a CDAI decrease from baseline of ≥ 100 points at week 1, 4, 8, 12, 13, 16, and 24. | The percentage of subjects achieving clinical response defined as a CDAI decrease from baseline of ≥ 100 points at week 1, 4, 8, 12, 13, 16, and 24. | week 1, 4, 8, 12, 13, 16, and 24 |