Trial Outcomes & Findings for Phase II Study of HMPL-004 in Patients With Ulcerative Colitis (NCT NCT00659802)
NCT ID: NCT00659802
Last Updated: 2020-07-22
Results Overview
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.
COMPLETED
PHASE2
224 participants
8 weeks
2020-07-22
Participant Flow
Patients were required to have mild to moderate ulcerative colitis to enter the study. Study was conducted at medical clinics and hospitals in the United States, Ukraine and Romania.
Participant milestones
| Measure |
High Dose HMPL-004 (1800 mg/Day)
HMPL-004 : HMPL-004, 600 mg (3 x 200 mg) t.i.d. total of 1800 mg/day.
|
Low Dose HMPL-004 (1200 mg/Day)
HMPL-004 : HMPL-004, 400 mg (2 x 200 mg) t.i.d. (total of 1200 mg/day).
|
Placebo
Placebo, t.i.d.
|
|---|---|---|---|
|
Overall Study
STARTED
|
74
|
75
|
75
|
|
Overall Study
COMPLETED
|
59
|
57
|
64
|
|
Overall Study
NOT COMPLETED
|
15
|
18
|
11
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase II Study of HMPL-004 in Patients With Ulcerative Colitis
Baseline characteristics by cohort
| Measure |
High Dose HMPL-004 (1800 mg/Day)
n=74 Participants
HMPL-004 : HMPL-004, 600 mg (3 x 200 mg) t.i.d. total of 1800 mg/day.
|
Low Dose HMPL-004 (1200 mg/Day)
n=74 Participants
HMPL-004 : HMPL-004, 400 mg (2 x 200 mg) t.i.d. (total of 1200 mg/day).
|
Placebo
n=75 Participants
Placebo, t.i.d.
|
Total
n=223 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
45.64 Years
STANDARD_DEVIATION 13.61 • n=5 Participants
|
44.3 Years
STANDARD_DEVIATION 14.5 • n=7 Participants
|
44.68 Years
STANDARD_DEVIATION 15.21 • n=5 Participants
|
44.87 Years
STANDARD_DEVIATION 14.4 • n=4 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
101 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
122 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Based on number of subjects with a non-missing value in each treatment group.
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.
Outcome measures
| Measure |
Low Dose HMPL-004 (1200 mg/Day)
n=60 Participants
HMPL-004 : HMPL-004, 400 mg (2 x 200 mg) t.i.d. (total of 1200 mg/day).
|
High Dose HMPL-004 (1800 mg/Day)
n=62 Participants
HMPL-004 : HMPL-004, 600 mg (3 x 200 mg) t.i.d. total of 1800 mg/day.
|
Placebo
n=69 Participants
Placebo, t.i.d.
|
|---|---|---|---|
|
Number of Participants With a Clinical Response at Week 8
|
33 Participants
|
45 Participants
|
30 Participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Based on number of subjects with a non-missing value in each treatment group.
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.
Outcome measures
| Measure |
Low Dose HMPL-004 (1200 mg/Day)
n=60 Participants
HMPL-004 : HMPL-004, 400 mg (2 x 200 mg) t.i.d. (total of 1200 mg/day).
|
High Dose HMPL-004 (1800 mg/Day)
n=62 Participants
HMPL-004 : HMPL-004, 600 mg (3 x 200 mg) t.i.d. total of 1800 mg/day.
|
Placebo
n=69 Participants
Placebo, t.i.d.
|
|---|---|---|---|
|
Number of Participants With a Clinical Remission at Week 8
|
25 Participants
|
28 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Based on number of subjects with a non-missing value in each treatment group.
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.
Outcome measures
| Measure |
Low Dose HMPL-004 (1200 mg/Day)
n=60 Participants
HMPL-004 : HMPL-004, 400 mg (2 x 200 mg) t.i.d. (total of 1200 mg/day).
|
High Dose HMPL-004 (1800 mg/Day)
n=62 Participants
HMPL-004 : HMPL-004, 600 mg (3 x 200 mg) t.i.d. total of 1800 mg/day.
|
Placebo
n=69 Participants
Placebo, t.i.d.
|
|---|---|---|---|
|
Number of Participants With Mucosal Healing at Week 8
|
28 Participants
|
37 Participants
|
25 Participants
|
Adverse Events
Low Dose HMPL-004 (1200 mg/Day)
High Dose HMPL-004 (1800 mg/Day)
Placebo
Serious adverse events
| Measure |
Low Dose HMPL-004 (1200 mg/Day)
n=75 participants at risk
HMPL-004 : HMPL-004, 400 mg (2 x 200 mg) t.i.d. (total of 1200 mg/day).
|
High Dose HMPL-004 (1800 mg/Day)
n=74 participants at risk
HMPL-004 : HMPL-004, 600 mg (3 x 200 mg) t.i.d. total of 1800 mg/day.
|
Placebo
n=75 participants at risk
Placebo, t.i.d.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
1.3%
1/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/75 • 12 weeks
|
1.4%
1/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
1.3%
1/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
1.3%
1/75 • 12 weeks
|
1.4%
1/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Infections and infestations
Pilonidal cyst
|
0.00%
0/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
1.3%
1/75 • 12 weeks
|
|
Investigations
Hematocrit decreased
|
0.00%
0/75 • 12 weeks
|
1.4%
1/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Investigations
Hemoglobin decreased
|
0.00%
0/75 • 12 weeks
|
1.4%
1/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/75 • 12 weeks
|
1.4%
1/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
1.3%
1/75 • 12 weeks
|
Other adverse events
| Measure |
Low Dose HMPL-004 (1200 mg/Day)
n=75 participants at risk
HMPL-004 : HMPL-004, 400 mg (2 x 200 mg) t.i.d. (total of 1200 mg/day).
|
High Dose HMPL-004 (1800 mg/Day)
n=74 participants at risk
HMPL-004 : HMPL-004, 600 mg (3 x 200 mg) t.i.d. total of 1800 mg/day.
|
Placebo
n=75 participants at risk
Placebo, t.i.d.
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.7%
2/75 • 12 weeks
|
1.4%
1/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.0%
3/75 • 12 weeks
|
4.1%
3/74 • 12 weeks
|
1.3%
1/75 • 12 weeks
|
|
General disorders
Chest discomfort
|
0.00%
0/75 • 12 weeks
|
2.7%
2/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
General disorders
Fatigue
|
2.7%
2/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
4.0%
3/75 • 12 weeks
|
|
General disorders
Edema peripheral
|
2.7%
2/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
1.3%
1/75 • 12 weeks
|
|
General disorders
Pyrexia
|
2.7%
2/75 • 12 weeks
|
2.7%
2/74 • 12 weeks
|
1.3%
1/75 • 12 weeks
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/75 • 12 weeks
|
1.4%
1/74 • 12 weeks
|
4.0%
3/75 • 12 weeks
|
|
Blood and lymphatic system disorders
Basophilia
|
0.00%
0/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
4.0%
3/75 • 12 weeks
|
|
Blood and lymphatic system disorders
Leukocytosis
|
2.7%
2/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/75 • 12 weeks
|
4.1%
3/74 • 12 weeks
|
4.0%
3/75 • 12 weeks
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/75 • 12 weeks
|
2.7%
2/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/75 • 12 weeks
|
2.7%
2/74 • 12 weeks
|
1.3%
1/75 • 12 weeks
|
|
Ear and labyrinth disorders
Vertigo
|
2.7%
2/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Gastrointestinal disorders
Abdominal distension
|
1.3%
1/75 • 12 weeks
|
2.7%
2/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
5.3%
4/75 • 12 weeks
|
5.4%
4/74 • 12 weeks
|
8.0%
6/75 • 12 weeks
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/75 • 12 weeks
|
1.4%
1/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
|
Gastrointestinal disorders
Constipation
|
2.7%
2/75 • 12 weeks
|
1.4%
1/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
4.0%
3/75 • 12 weeks
|
5.4%
4/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
|
Gastrointestinal disorders
Dyspepsia
|
4.0%
3/75 • 12 weeks
|
1.4%
1/74 • 12 weeks
|
1.3%
1/75 • 12 weeks
|
|
Gastrointestinal disorders
Flatulence
|
1.3%
1/75 • 12 weeks
|
5.4%
4/74 • 12 weeks
|
1.3%
1/75 • 12 weeks
|
|
Gastrointestinal disorders
Nausea
|
5.3%
4/75 • 12 weeks
|
4.1%
3/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
1.3%
1/75 • 12 weeks
|
2.7%
2/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Gastrointestinal disorders
Vomiting
|
1.3%
1/75 • 12 weeks
|
2.7%
2/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Nervous system disorders
Ageusia
|
4.0%
3/75 • 12 weeks
|
2.7%
2/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Nervous system disorders
Dizziness
|
2.7%
2/75 • 12 weeks
|
1.4%
1/74 • 12 weeks
|
1.3%
1/75 • 12 weeks
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/75 • 12 weeks
|
4.1%
3/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Nervous system disorders
Headache
|
10.7%
8/75 • 12 weeks
|
5.4%
4/74 • 12 weeks
|
6.7%
5/75 • 12 weeks
|
|
Nervous system disorders
Migraine
|
0.00%
0/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
|
Infections and infestations
Influenza
|
2.7%
2/75 • 12 weeks
|
2.7%
2/74 • 12 weeks
|
5.3%
4/75 • 12 weeks
|
|
Infections and infestations
Nasopharyngitis
|
2.7%
2/75 • 12 weeks
|
2.7%
2/74 • 12 weeks
|
4.0%
3/75 • 12 weeks
|
|
Investigations
Alanine aminotransferase increased
|
4.0%
3/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Investigations
Aspartate aminotransferase increased
|
2.7%
2/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Investigations
Blood alkaline phosphatase increased
|
4.0%
3/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
1.3%
1/75 • 12 weeks
|
|
Investigations
Blood glucose increased
|
0.00%
0/75 • 12 weeks
|
4.1%
3/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Investigations
Blood urea increased
|
1.3%
1/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
|
Investigations
C-reactive protein increased
|
1.3%
1/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
|
Investigations
Gamma-glutamyl transferase increased
|
4.0%
3/75 • 12 weeks
|
1.4%
1/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
|
Investigations
Hematocrit decreased
|
0.00%
0/75 • 12 weeks
|
2.7%
2/74 • 12 weeks
|
1.3%
1/75 • 12 weeks
|
|
Investigations
Hemoglobin decreased
|
0.00%
0/75 • 12 weeks
|
2.7%
2/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Investigations
Hepatic enzyme increased
|
2.7%
2/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
0.00%
0/75 • 12 weeks
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/75 • 12 weeks
|
0.00%
0/74 • 12 weeks
|
2.7%
2/75 • 12 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place