Trial Outcomes & Findings for Phase II Study of HMPL-004 in Subjects With Crohn's Disease (NCT NCT00655733)

NCT ID: NCT00655733

Last Updated: 2020-01-02

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 101 participants
• Primary outcome timeframe: 8 weeks
• Results posted on: 2020-01-02

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	51	50
Overall Study COMPLETED	44	42
Overall Study NOT COMPLETED	7	8

Reasons for withdrawal

Measure	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.	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.
Overall Study Lost to Follow-up	2	2
Overall Study Adverse Event	2	2
Overall Study Withdrawal by Subject	3	3
Overall Study Physician Decision	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.	Total n=101 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	49 Participants n=5 Participants	44 Participants n=7 Participants	93 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Age, Continuous	42.4 years STANDARD_DEVIATION 13.4 • n=5 Participants	46.5 years STANDARD_DEVIATION 14.2 • n=7 Participants	44.4 years STANDARD_DEVIATION 13.9 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	29 Participants n=7 Participants	57 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	21 Participants n=7 Participants	44 Participants n=5 Participants
Region of Enrollment United States	38 participants n=5 Participants	35 participants n=7 Participants	73 participants n=5 Participants
Region of Enrollment Ukraine	13 participants n=5 Participants	15 participants n=7 Participants	28 participants n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: Intention-to-treat (ITT)

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.

Outcome measures

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.
CDAI Clinical Response -100 at Week 8	19 Participants	11 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: ITT

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.

Outcome measures

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.
Clinical Response -100 at Weeks 4	15 Participants	13 Participants

SECONDARY outcome

Timeframe: 12 weeks

Population: ITT

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.

Outcome measures

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.
Clinical Response -100 at Weeks 12	17 Participants	11 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: ITT

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.

Outcome measures

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.
Remission at Week 4	8 Participants	8 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: ITT

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.

Outcome measures

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.
Remission at Week 8	15 Participants	7 Participants

SECONDARY outcome

Timeframe: 12 weeks

Population: ITT

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.

Outcome measures

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.
Remission at Week 12	10 Participants	7 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: ITT

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.

Outcome measures

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.
Clinical Response -70 at Week 4	20 Participants	19 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: ITT

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.

Outcome measures

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.
Clinical Response -70 at Week 8	25 Participants	16 Participants

SECONDARY outcome

Timeframe: 12 weeks

Population: ITT

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.

Outcome measures

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.
Clinical Response -70 at Week 12	20 Participants	18 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: ITT

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.

Outcome measures

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.
Complete Remission at Week 4	8 Participants	8 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: ITT

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.

Outcome measures

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.
Complete Remission at Week 8	13 Participants	7 Participants

SECONDARY outcome

Timeframe: 12 weeks

Population: ITT

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.

Outcome measures

Measure	HMPL-004 n=51 Participants 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.	Placebo n=50 Participants 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.
Complete Remission at Week 12	9 Participants	5 Participants

Adverse Events

HMPL-004

Serious events: 2 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	HMPL-004 n=51 participants at risk 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.	Placebo n=50 participants at risk 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.
Blood and lymphatic system disorders Anaemia	2.0% 1/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	0.00% 0/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.
Reproductive system and breast disorders Female genital tract fistula	3.6% 1/28 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	0.00% 0/29 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung squamous cell carcinoma stage unspecified	0.00% 0/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	2.0% 1/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.
Gastrointestinal disorders Crohn's disease (flare)	0.00% 0/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	2.0% 1/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	2.0% 1/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	2.0% 1/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.

Other adverse events

Measure	HMPL-004 n=51 participants at risk 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.	Placebo n=50 participants at risk 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.
Gastrointestinal disorders Abdominal pain	5.9% 3/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	6.0% 3/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.
General disorders Vomiting	5.9% 3/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	4.0% 2/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.
General disorders Pyrexia	9.8% 5/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	2.0% 1/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.
Infections and infestations Nasopharyngitis	9.8% 5/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	2.0% 1/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.
Infections and infestations Urinary Tract Infection	5.9% 3/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	2.0% 1/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.
Nervous system disorders Headache	5.9% 3/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	4.0% 2/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.
Gastrointestinal disorders Nausea	3.9% 2/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	10.0% 5/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.
Infections and infestations Upper respiratory tract infection	3.9% 2/51 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.	6.0% 3/50 • From subject randomization through 8 weeks of treatment and through the 30 day follow up period following the date of the last dose of study drug was taken.

Additional Information

Hua Mu,Senior Vice President of Clinical Research and Development

Hutchison MediPharma

Phone: 861 3564487805

Email: huam@hmplglobal.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60