Trial Outcomes & Findings for A Phase III Trial of HMPL-004 in Patients With Mild to Moderate Active Ulcerative Colitis (NCT NCT01805791)
NCT ID: NCT01805791
Last Updated: 2020-01-02
Results Overview
Clinical remission was defined as a total Mayo Score of ≤2 points with no individual sub-score \>1 point and rectal bleeding score = 0.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
201 participants
Primary outcome timeframe
8 weeks
Results posted on
2020-01-02
Participant Flow
Participant milestones
| Measure |
Placebo
Placebo, oral tablets, three times a day
Placebo: Subjects randomized to the arm of Placebo will receive matching Placebo three times daily for 56 days (8 weeks).
|
HMPL-004 1800 mg/Day
1 600 mg HMPL-004 tablet, 2x400 mg placebo tablets taken 3 times a day
HMPL-004 1800 mg/day: Subjects randomized to the arm of HMPL-004 1800 mg/day will receive HMPL-004 600 mg 3 times daily (total dose 1800 mg/day) for 56 days (8 weeks).
|
HMPL-004 2400 mg/Day
2 x 400 mg HMPL tablets, 1 x 600 mg placebo tablet, taken 3 times per day
HMPL-004 2400 mg/day: Subjects randomized to the arm of HMPL-004 2400 mg/day will receive HMPL-004 800 mg 3 times daily (total dose 2400 mg/day) for 56 days (8 weeks).
|
|---|---|---|---|
|
Overall Study
STARTED
|
66
|
67
|
68
|
|
Overall Study
COMPLETED
|
44
|
50
|
48
|
|
Overall Study
NOT COMPLETED
|
22
|
17
|
20
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Phase III Trial of HMPL-004 in Patients With Mild to Moderate Active Ulcerative Colitis
Baseline characteristics by cohort
| Measure |
Placebo
n=66 Participants
Placebo, oral tablets, 3 times a day
Placebo: Subjects randomized to the arm of Placebo will receive matching Placebo three times daily for 56 days (8 weeks).
|
HMPL-004 1800 mg/Day
n=67 Participants
1 600 mg HMPL-004 tablet, 2x400 mg placebo tablets taken 3 times a day
HMPL-004 1800 mg/day: Subjects randomized to the arm of HMPL-004 1800 mg/day will receive HMPL-004 600 mg 3 times a day (total dose 1800 mg/day) for 56 days (8 weeks).
|
HMPL-004 2400 mg/Day
n=68 Participants
2 x 400 mg HMPL tablets, 1 x 600 mg placebo tablet, taken 3 times a day
HMPL-004 2400 mg/day: Subjects randomized to the arm of HMPL-004 2400 mg/day will receive HMPL-004 800 mg 3 times a day (total dose 2400 mg/day) for 56 days (8 weeks).
|
Total
n=201 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
45.3 years
STANDARD_DEVIATION 16.32 • n=99 Participants
|
43.9 years
STANDARD_DEVIATION 15.07 • n=107 Participants
|
40.6 years
STANDARD_DEVIATION 12.33 • n=206 Participants
|
43.2 years
STANDARD_DEVIATION 14.70 • n=7 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=99 Participants
|
37 Participants
n=107 Participants
|
33 Participants
n=206 Participants
|
93 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
43 Participants
n=99 Participants
|
30 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
108 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
28 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
57 Participants
n=99 Participants
|
58 Participants
n=107 Participants
|
58 Participants
n=206 Participants
|
173 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
14 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
62 Participants
n=99 Participants
|
63 Participants
n=107 Participants
|
55 Participants
n=206 Participants
|
180 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
|
Current Smoker: Yes, No
Yes
|
6 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
11 Participants
n=7 Participants
|
|
Current Smoker: Yes, No
No
|
60 Participants
n=99 Participants
|
63 Participants
n=107 Participants
|
67 Participants
n=206 Participants
|
190 Participants
n=7 Participants
|
|
Weight, Continuous
|
80.94 kg
STANDARD_DEVIATION 16.00 • n=99 Participants
|
79.77 kg
STANDARD_DEVIATION 19.35 • n=107 Participants
|
82.24 kg
STANDARD_DEVIATION 21.42 • n=206 Participants
|
80.99 kg
STANDARD_DEVIATION 19.01 • n=7 Participants
|
|
Height, Continuous
|
172.21 cm
STANDARD_DEVIATION 10.30 • n=99 Participants
|
170.67 cm
STANDARD_DEVIATION 9.54 • n=107 Participants
|
170.28 cm
STANDARD_DEVIATION 8.74 • n=206 Participants
|
171.05 cm
STANDARD_DEVIATION 9.53 • n=7 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Analysis included only those subjects who were randomized on or prior to 16 Jun 2014 and had an opportunity to complete the 8 week treatment period. Worst case imputation imputed any missing Week 8 value as a failure.
Clinical remission was defined as a total Mayo Score of ≤2 points with no individual sub-score \>1 point and rectal bleeding score = 0.
Outcome measures
| Measure |
HMPL-004 2400 mg/Day
n=57 Participants
2 x 400 mg HMPL tablets, 1 x 600 mg placebo tablet, taken 3 times a day
HMPL-004 2400 mg/day: Subjects randomized to the arm of HMPL-004 2400 mg/day will receive HMPL-004 800 mg 3 times a day (total dose 2400 mg/day) for 56 days (8 weeks).
|
HMPL-004 1800 mg/Day
n=58 Participants
1 600 mg HMPL-004 tablet, 2x400 mg placebo tablets taken 3 times a day
HMPL-004 1800 mg/day: Subjects randomized to the arm of HMPL-004 1800 mg/day will receive HMPL-004 600 mg 3 times a day (total dose 1800 mg/day) for 56 days (8 weeks).
|
Placebo
n=52 Participants
Placebo, oral tablets, 3 times a day
Placebo: Subjects randomized to the arm of Placebo will receive matching Placebo 3 times a day for 56 days (8 weeks).
|
|---|---|---|---|
|
Percentage of Subjects With a Clinical Remission at Week 8
|
9 Participants
|
7 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Analysis included only those subjects who were randomized on or prior to 16 Jun 2014 and had an opportunity to complete the 8 week treatment period. Worst case imputation imputed any missing Week 8 value as a failure.
Clinical response was defined as a decrease in a modified Mayo Score from baseline by ≥3 points and ≥30% decrease in the modified Mayo Score, along with either a decrease in the rectal bleeding score ≥1 or an absolute rectal bleeding score ≤1.
Outcome measures
| Measure |
HMPL-004 2400 mg/Day
n=57 Participants
2 x 400 mg HMPL tablets, 1 x 600 mg placebo tablet, taken 3 times a day
HMPL-004 2400 mg/day: Subjects randomized to the arm of HMPL-004 2400 mg/day will receive HMPL-004 800 mg 3 times a day (total dose 2400 mg/day) for 56 days (8 weeks).
|
HMPL-004 1800 mg/Day
n=58 Participants
1 600 mg HMPL-004 tablet, 2x400 mg placebo tablets taken 3 times a day
HMPL-004 1800 mg/day: Subjects randomized to the arm of HMPL-004 1800 mg/day will receive HMPL-004 600 mg 3 times a day (total dose 1800 mg/day) for 56 days (8 weeks).
|
Placebo
n=52 Participants
Placebo, oral tablets, 3 times a day
Placebo: Subjects randomized to the arm of Placebo will receive matching Placebo 3 times a day for 56 days (8 weeks).
|
|---|---|---|---|
|
The Proportion of Subjects With Clinical Response at Week 8
|
23 Participants
|
19 Participants
|
16 Participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Analysis included only those subjects who were randomized on or prior to 16 Jun 2014 and had an opportunity to complete the 8 week treatment period. Worst case imputation imputed any missing Week 8 value as a failure.
Mucosal healing was defined as having normal or inactive disease using a modified Mayo Score to determine if the decrease in the modified Mayo endoscopy sub-score from baseline was ≥1 in at least 1 segment and had an absolute score ≤1 in all segments.
Outcome measures
| Measure |
HMPL-004 2400 mg/Day
n=57 Participants
2 x 400 mg HMPL tablets, 1 x 600 mg placebo tablet, taken 3 times a day
HMPL-004 2400 mg/day: Subjects randomized to the arm of HMPL-004 2400 mg/day will receive HMPL-004 800 mg 3 times a day (total dose 2400 mg/day) for 56 days (8 weeks).
|
HMPL-004 1800 mg/Day
n=58 Participants
1 600 mg HMPL-004 tablet, 2x400 mg placebo tablets taken 3 times a day
HMPL-004 1800 mg/day: Subjects randomized to the arm of HMPL-004 1800 mg/day will receive HMPL-004 600 mg 3 times a day (total dose 1800 mg/day) for 56 days (8 weeks).
|
Placebo
n=52 Participants
Placebo, oral tablets, 3 times a day
Placebo: Subjects randomized to the arm of Placebo will receive matching Placebo 3 times a day for 56 days (8 weeks).
|
|---|---|---|---|
|
The Proportion of Subjects With Mucosal Healing at Week 8
|
13 Participants
|
13 Participants
|
14 Participants
|
Adverse Events
HMPL-004 2400 mg/Day
Serious events: 0 serious events
Other events: 31 other events
Deaths: 0 deaths
HMPL-004 1800 mg/Day
Serious events: 0 serious events
Other events: 25 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
HMPL-004 2400 mg/Day
n=68 participants at risk
2 x 400 mg HMPL tablets, 1 x 600 mg placebo tablet, taken 3 times a day
HMPL-004 2400 mg/day: Subjects randomized to the arm of HMPL-004 2400 mg/day will receive HMPL-004 800 mg 3 times a day (total dose 2400 mg/day) for 56 days (8 weeks).
|
HMPL-004 1800 mg/Day
n=67 participants at risk
1 600 mg HMPL-004 tablet, 2x400 mg placebo tablets taken 3 times a day
HMPL-004 1800 mg/day: Subjects randomized to the arm of HMPL-004 1800 mg/day will receive HMPL-004 600 mg 3 times a day (total dose 1800 mg/day) for 56 days (8 weeks).
|
Placebo
n=66 participants at risk
Placebo, oral tablets, 3 times a day
Placebo: Subjects randomized to the arm of Placebo will receive matching Placebo 3 times a day for 56 days (8 weeks).
|
|---|---|---|---|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/68 • 86 days
|
0.00%
0/67 • 86 days
|
1.5%
1/66 • 86 days
|
|
General disorders
Pyrexia
|
0.00%
0/68 • 86 days
|
0.00%
0/67 • 86 days
|
1.5%
1/66 • 86 days
|
|
Infections and infestations
Appendicitis
|
0.00%
0/68 • 86 days
|
0.00%
0/67 • 86 days
|
1.5%
1/66 • 86 days
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/68 • 86 days
|
0.00%
0/67 • 86 days
|
1.5%
1/66 • 86 days
|
Other adverse events
| Measure |
HMPL-004 2400 mg/Day
n=68 participants at risk
2 x 400 mg HMPL tablets, 1 x 600 mg placebo tablet, taken 3 times a day
HMPL-004 2400 mg/day: Subjects randomized to the arm of HMPL-004 2400 mg/day will receive HMPL-004 800 mg 3 times a day (total dose 2400 mg/day) for 56 days (8 weeks).
|
HMPL-004 1800 mg/Day
n=67 participants at risk
1 600 mg HMPL-004 tablet, 2x400 mg placebo tablets taken 3 times a day
HMPL-004 1800 mg/day: Subjects randomized to the arm of HMPL-004 1800 mg/day will receive HMPL-004 600 mg 3 times a day (total dose 1800 mg/day) for 56 days (8 weeks).
|
Placebo
n=66 participants at risk
Placebo, oral tablets, 3 times a day
Placebo: Subjects randomized to the arm of Placebo will receive matching Placebo 3 times a day for 56 days (8 weeks).
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
5.9%
4/68 • 86 days
|
3.0%
2/67 • 86 days
|
4.5%
3/66 • 86 days
|
|
Gastrointestinal disorders
Abdominal pain
|
4.4%
3/68 • 86 days
|
1.5%
1/67 • 86 days
|
3.0%
2/66 • 86 days
|
|
Gastrointestinal disorders
Nausea
|
2.9%
2/68 • 86 days
|
3.0%
2/67 • 86 days
|
6.1%
4/66 • 86 days
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
4.4%
3/68 • 86 days
|
1.5%
1/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Gastrointestinal disorders
Vomiting
|
4.4%
3/68 • 86 days
|
1.5%
1/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.4%
3/68 • 86 days
|
0.00%
0/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/68 • 86 days
|
3.0%
2/67 • 86 days
|
3.0%
2/66 • 86 days
|
|
Gastrointestinal disorders
Dry mouth
|
2.9%
2/68 • 86 days
|
0.00%
0/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/68 • 86 days
|
3.0%
2/67 • 86 days
|
1.5%
1/66 • 86 days
|
|
Gastrointestinal disorders
Flatulence
|
2.9%
2/68 • 86 days
|
0.00%
0/67 • 86 days
|
1.5%
1/66 • 86 days
|
|
Gastrointestinal disorders
GERD
|
2.9%
2/68 • 86 days
|
0.00%
0/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Infections and infestations
Nasopharyngitis
|
2.9%
2/68 • 86 days
|
1.5%
1/67 • 86 days
|
1.5%
1/66 • 86 days
|
|
Infections and infestations
Sinusitis
|
2.9%
2/68 • 86 days
|
0.00%
0/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/68 • 86 days
|
3.0%
2/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/68 • 86 days
|
0.00%
0/67 • 86 days
|
3.0%
2/66 • 86 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.9%
2/68 • 86 days
|
1.5%
1/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.9%
2/68 • 86 days
|
1.5%
1/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/68 • 86 days
|
3.0%
2/67 • 86 days
|
3.0%
2/66 • 86 days
|
|
Nervous system disorders
Dizziness
|
2.9%
2/68 • 86 days
|
3.0%
2/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Nervous system disorders
Dysgeusia
|
4.4%
3/68 • 86 days
|
0.00%
0/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
General disorders
Fatigue
|
2.9%
2/68 • 86 days
|
1.5%
1/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
General disorders
Pyrexia
|
2.9%
2/68 • 86 days
|
0.00%
0/67 • 86 days
|
1.5%
1/66 • 86 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/68 • 86 days
|
3.0%
2/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.9%
2/68 • 86 days
|
0.00%
0/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Blood and lymphatic system disorders
Anaemia
|
2.9%
2/68 • 86 days
|
1.5%
1/67 • 86 days
|
1.5%
1/66 • 86 days
|
|
Psychiatric disorders
Depression
|
2.9%
2/68 • 86 days
|
1.5%
1/67 • 86 days
|
0.00%
0/66 • 86 days
|
|
Psychiatric disorders
Insomnia
|
2.9%
2/68 • 86 days
|
0.00%
0/67 • 86 days
|
1.5%
1/66 • 86 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place