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

Phase 2

Completed

• Conditions: Crohn's Disease
• Interventions: Drug: Placebo; Drug: HMPL-004

• Registration Number: NCT00655733
• Lead Sponsor: Hutchison Medipharma Limited

Brief Summary

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

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.

Study Timeline

• Study Start: 2006-04
• Study First Submitted: 2008-04-06
• Study First Submitted QC: 2008-04-09
• Study First Posted: 2008-04-10
• Primary Completion: 2009-04
• Study Completion: 2009-04
• Results First Submitted: 2011-04-18
• Results First Submitted QC: 2012-11-04
• Results First Posted: 2012-12-03
• Status Verified: 2018-08
• Last Update Submitted: 2019-12-26
• Last Update Posted: 2020-01-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 101

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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.
HMPL-004	HMPL-004	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.

Primary Outcome Measures

Name	Time	Method
CDAI Clinical Response -100 at Week 8	8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Clinical Response -100 at Weeks 4	4 weeks	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.
Clinical Response -100 at Weeks 12	12 weeks	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.
Remission at Week 4	4 weeks	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.
Remission at Week 8	8 weeks	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.
Remission at Week 12	12 weeks	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.
Clinical Response -70 at Week 4	4 weeks	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.
Clinical Response -70 at Week 8	8 weeks	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.
Clinical Response -70 at Week 12	12 weeks	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.
Complete Remission at Week 4	4 weeks	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.
Complete Remission at Week 8	8 weeks	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.
Complete Remission at Week 12	12 weeks	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.