Phase II Study of HMPL-004 in Subjects With Crohn's Disease

Study Overview
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Brief Summary
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A double blind, randomized, multi-center, placebo-controlled study to evaluate the efficacy and safety of HMPL-004 in patients with active moderate Crohn's Disease.

Detailed Description
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This was a double-blind, randomized, multicenter, placebo-controlled study evaluating the efficacy and safety of oral HMPL-004 in subjects with active moderate Crohn's disease (CD) - Crohn's Disease Activity Index (CDAI) 220 to 400 - on stable doses of CD medications who had not received anti-tumor necrosis factor alpha (anti-TNF-α) for at least 3 months prior to start of treatment. HMPL-004 (or placebo) was added to the subject's existing CD medications. Subjects were observed for an 8-week treatment period and a subsequent 4-week follow-up period.

Official Title
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Double-blind, Randomized, Multicenter, Placebo-controlled Phase II Study of Efficacy and Safety of HMPL-004 in Subjects With Active Moderate Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: HMPL-004
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have active confirmed Crohn's Disease (confirmed radiographically, endoscopic, or histologically), with a CDAI of 220-400 at baseline screen Exclusion Criteria: They have received anti-TNF-α antibody within 3 months of starting study medication, or cyclosporine, tacrolimus, thalidomide or mycophenolate mofetil within 2 months of starting study medication

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 |
| --- | --- |
| Experimental: HMPL-004<br>Subjects who fulfilled all entry criteria and randomized HMPL-004 arm will receive HMPL-004 400 mg 3 times daily 3 times daily for 56 days (8 weeks) with a 28-day (4-week) follow-up. | Drug: HMPL-004<br>* HMPL-004 1200 mg/d<br>* Other names: Chuan xinlian;|
| Placebo Comparator: Placebo<br>Subjects who fulfilled all entry criteria and randomized Placebo arm will receive matching placebo 400 mg 3 times daily 3 times daily for 56 days (8 weeks) with a 28-day (4-week) follow-up. | Drug: Placebo<br>* Placebo 1200 mg/d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CDAI Clinical Response -100 at Week 8 | Percentage of subjects with CDAI clinical response -100 at Week 8 based on ITT population using the WOCF method to impute missing CDAI scores at Week 8. Clinical response -100 was defined as CDAI score decrease of ≥100 points from baseline in subjects who had no change in concomitant medications for Crohn's disease except for steroids, which could be tapered after Week 8. The CDAI consists of eight variables, including Liquid or very soft stools, Abdominal pain, General well-being, Features of extra-intestinal disease, Oplates for diarrhea, Abdominal mass, Hematocrit and Body weight below standard, each weighted according to its ability to be predictive of disease activity. The total score ranges from 0 to over 600 with higher scores indicating higher disease activity or worse outcome. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response -100 at Weeks 4 | Percentage of subjects with CDAI clinical response -100 at Week 4 based on ITT population using the WOCF method to impute missing CDAI scores at Week 4. Clinical response -100 was defined as CDAI score decrease of ≥100 points from baseline in subjects who had no change in concomitant medications for Crohn's disease except for steroids, which could be tapered after Week 8. The CDAI consists of eight variables, including Liquid or very soft stools, Abdominal pain, General well-being, Features of extra-intestinal disease, Oplates for diarrhea, Abdominal mass, Hematocrit and Body weight below standard, each weighted according to its ability to be predictive of disease activity. The total score ranges from 0 to over 600 with higher scores indicating higher disease activity or worse outcome. | 4 weeks | 
| Clinical Response -100 at Weeks 12 | Percentage of subjects with CDAI clinical response -100 at Week 12 based on ITT population using the WOCF method to impute missing CDAI scores at Week 12. Clinical response -100 was defined as CDAI score decrease of ≥100 points from baseline in subjects who had no change in concomitant medications for Crohn's disease except for steroids, which could be tapered after Week 8. The CDAI consists of eight variables, including Liquid or very soft stools, Abdominal pain, General well-being, Features of extra-intestinal disease, Oplates for diarrhea, Abdominal mass, Hematocrit and Body weight below standard, each weighted according to its ability to be predictive of disease activity. The total score ranges from 0 to over 600 with higher scores indicating higher disease activity or worse outcome. | 12 weeks | 
| Remission at Week 4 | Percentage of subjects achieving remission (CDAI<150) at week 4. Remission was defined as CDAI score <150 in subjects who had no change in concomitant medications for Crohn's disease except for steroids, which could be tapered after Week 8. The CDAI consists of eight variables, including Liquid or very soft stools, Abdominal pain, General well-being, Features of extra-intestinal disease, Oplates for diarrhea, Abdominal mass, Hematocrit and Body weight below standard, each weighted according to its ability to be predictive of disease activity. The total score ranges from 0 to over 600 with higher scores indicating higher disease activity or worse outcome. | 4 weeks | 
| Remission at Week 8 | Percentage of subjects achieving remission (CDAI<150) at week 8. Remission was defined as CDAI score <150 in subjects who had no change in concomitant medications for Crohn's disease except for steroids, which could be tapered after Week 8. The CDAI consists of eight variables, including Liquid or very soft stools, Abdominal pain, General well-being, Features of extra-intestinal disease, Oplates for diarrhea, Abdominal mass, Hematocrit and Body weight below standard, each weighted according to its ability to be predictive of disease activity. The total score ranges from 0 to over 600 with higher scores indicating higher disease activity or worse outcome. | 8 weeks | 
| Remission at Week 12 | Percentage of subjects achieving remission (CDAI<150) at week 12. Remission was defined as CDAI score <150 in subjects who had no change in concomitant medications for Crohn's disease except for steroids, which could be tapered after Week 8. The CDAI consists of eight variables, including Liquid or very soft stools, Abdominal pain, General well-being, Features of extra-intestinal disease, Oplates for diarrhea, Abdominal mass, Hematocrit and Body weight below standard, each weighted according to its ability to be predictive of disease activity. The total score ranges from 0 to over 600 with higher scores indicating higher disease activity or worse outcome. | 12 weeks | 
| Clinical Response -70 at Week 4 | Percentage of patients achieving clinical response -70 at Week 4 (WOCF). Clinical response -70 was defined as CDAI score decrease of ≥70 points from baseline in subjects who had no change in concomitant medications for Crohn's disease except for steroids, which could be tapered after Week 8. The CDAI consists of eight variables, including Liquid or very soft stools, Abdominal pain, General well-being, Features of extra-intestinal disease, Oplates for diarrhea, Abdominal mass, Hematocrit and Body weight below standard, each weighted according to its ability to be predictive of disease activity. The total score ranges from 0 to over 600 with higher scores indicating higher disease activity or worse outcome. | 4 weeks | 
| Clinical Response -70 at Week 8 | Percentage of patients achieving clinical response -70 at Week 8 (WOCF). Clinical response -70 was defined as CDAI score decrease of ≥70 points from baseline in subjects who had no change in concomitant medications for Crohn's disease except for steroids, which could be tapered after Week 8. The CDAI consists of eight variables, including Liquid or very soft stools, Abdominal pain, General well-being, Features of extra-intestinal disease, Oplates for diarrhea, Abdominal mass, Hematocrit and Body weight below standard, each weighted according to its ability to be predictive of disease activity. The total score ranges from 0 to over 600 with higher scores indicating higher disease activity or worse outcome. | 8 weeks | 
| Clinical Response -70 at Week 12 | Percentage of patients achieving clinical response -70 at Week 12 (WOCF). Clinical response -70 was defined as CDAI score decrease of ≥70 points from baseline in subjects who had no change in concomitant medications for Crohn's disease except for steroids, which could be tapered after Week 8. The CDAI consists of eight variables, including Liquid or very soft stools, Abdominal pain, General well-being, Features of extra-intestinal disease, Oplates for diarrhea, Abdominal mass, Hematocrit and Body weight below standard, each weighted according to its ability to be predictive of disease activity. The total score ranges from 0 to over 600 with higher scores indicating higher disease activity or worse outcome. | 12 weeks | 
| Complete Remission at Week 4 | Percentage of subjects achieving complete remission (clinical response -100 plus CDAI<150) at week 4 (WOCF). Complete remission was defined as CDAI score decrease of ≥100 points from baseline and CDAI score <150 in subjects who had no change in concomitant medications for Crohn's disease except for steroids, which could be tapered after Week 8. The CDAI consists of eight variables, including Liquid or very soft stools, Abdominal pain, General well-being, Features of extra-intestinal disease, Oplates for diarrhea, Abdominal mass, Hematocrit and Body weight below standard, each weighted according to its ability to be predictive of disease activity. The total score ranges from 0 to over 600 with higher scores indicating higher disease activity or worse outcome. | 4 weeks | 
| Complete Remission at Week 8 | Percentage of subjects achieving complete remission (clinical response -100 plus CDAI<150) at week 8 (WOCF). Complete remission was defined as CDAI score decrease of ≥100 points from baseline and CDAI score <150 in subjects who had no change in concomitant medications for Crohn's disease except for steroids, which could be tapered after Week 8. The CDAI consists of eight variables, including Liquid or very soft stools, Abdominal pain, General well-being, Features of extra-intestinal disease, Oplates for diarrhea, Abdominal mass, Hematocrit and Body weight below standard, each weighted according to its ability to be predictive of disease activity. The total score ranges from 0 to over 600 with higher scores indicating higher disease activity or worse outcome. | 8 weeks | 
| Complete Remission at Week 12 | Percentage of subjects achieving complete remission (clinical response -100 plus CDAI<150) at week 12 (WOCF). Complete remission was defined as CDAI score decrease of ≥100 points from baseline and CDAI score <150 in subjects who had no change in concomitant medications for Crohn's disease except for steroids, which could be tapered after Week 8. The CDAI consists of eight variables, including Liquid or very soft stools, Abdominal pain, General well-being, Features of extra-intestinal disease, Oplates for diarrhea, Abdominal mass, Hematocrit and Body weight below standard, each weighted according to its ability to be predictive of disease activity. The total score ranges from 0 to over 600 with higher scores indicating higher disease activity or worse outcome. | 12 weeks |