Phase II Study of HMPL-004 in Patients With Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of HMPL-004 in patients with active mild to moderate ulcerative colitis (UC), compared with placebo.

Detailed Description
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This is a double-blind, randomized, placebo-controlled Phase II study conducted in North America (U.S. and Canada) and Europe (Romania and Ukraine) in patients with mild to moderate ulcerative colitis. Treatment consisted of one of 2 doses of HMPL-004 (1200 mg daily or 1800 mg daily, administered in 3 divided doses) or matching placebo. Assessment of treatment effect is based on the Mayo score. Subjects eligible for the study will include those ≥18 years of age with mild to moderate ulcerative colitis, having a Mayo score of 4 to 10, with activity confirmed by endoscopy within 2 weeks prior to study entry, and having a Mayo endoscopy score ≥1. Subjects who are using concomitant mesalamine could enter the study. The randomization will be stratified by mesalamine use or non-use.

Official Title
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A Phase II, Randomized, Multi-Centre, Double-Blind, Placebo-Controlled Trial of HMPL-004 in Patients With Mild to Moderate Active Ulcerative Colitis With or Without Mesalamine

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: HMPL-004 low dose
* Drug: Placebo
* Drug: HMPL-004 high dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have active confirmed mild to moderate ulcerative colitis Exclusion Criteria: Diagnosed with Crohn's Disease or

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>Matching dose of placebo will be given orally in capsules three times per day for 56 days. | Drug: Placebo<br>* Matching dose of Placebo<br>|
| Experimental: HMPL-004 low dose<br>A total of 1200 mg of HMPL-004 per day in three divided doses will be given orally in capsules, 200 mg each, for 56 days. | Drug: HMPL-004 low dose<br>* HMPL-004, 400 mg (2 x 200 mg) t.i.d. (total of 1200 mg/day).<br>* Other names: Chuan xinlian;|
| Experimental: HMPL-004 high dose<br>A total of 1800 mg of HMPL-004 per day in three divided doses will be given orally in capsules, 200 mg each, for 56 days. | Drug: HMPL-004 high dose<br>* HMPL-004, 600 mg (3 x 200 mg) t.i.d. (total of 1800 mg/day).<br>* Other names: Chuan xinlian;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Clinical Response at Week 8 | Clinical response at week 8, which is a decrease in the Mayo score from the baseline by ≥ 3 points AND ≥ 30% decrease in the Mayo score along with either a decrease in the rectal bleeding score ≥ 1 OR an absolute rectal bleeding score ≤ 1. The full Mayo Score evaluates ulcerative colitis stage, based on four parameters: stool frequency (0-3), rectal bleeding (0-3), endoscopic evaluation (0-3) and Physician's global assessment (0-3), ranging from 0 to 12. The higher score means a higher disease activity or worse outcome. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Clinical Remission at Week 8 | The percentage of subjects exhibiting clinical remission (Mayo score ≤2 with no individual score >1) at week 8. The full Mayo Score evaluates ulcerative colitis stage, based on four parameters: stool frequency (0-3), rectal bleeding (0-3), endoscopic evaluation (0-3) and Physician's global assessment (0-3), ranging from 0 to 12. The higher score means a higher disease activity or worse outcome. | 8 weeks | 
| Number of Participants With Mucosal Healing at Week 8 | The percentage of subjects achieving Mucosal Healing at week 8. Mucosal Healing was defined as a significant decrease from baseline in the Mayo endoscopy sub-score ≥1 and absolute score ≤1. Mayo endoscopy sub-score ranges from 0 to 12. The higher score means a higher disease activity or worse outcome. | 8 weeks |