Ulcerative Colitis
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of HMPL-004 in patients with active mild to moderate ulcerative colitis (UC), compared with placebo.
Detailed description
This is a double-blind, randomized, placebo-controlled Phase II study conducted in North America (U.S. and Canada) and Europe (Romania and Ukraine) in patients with mild to moderate ulcerative colitis. Treatment consisted of one of 2 doses of HMPL-004 (1200 mg daily or 1800 mg daily, administered in 3 divided doses) or matching placebo. Assessment of treatment effect is based on the Mayo score. Subjects eligible for the study will include those ≥18 years of age with mild to moderate ulcerative colitis, having a Mayo score of 4 to 10, with activity confirmed by endoscopy within 2 weeks prior to study entry, and having a Mayo endoscopy score ≥1. Subjects who are using concomitant mesalamine could enter the study. The randomization will be stratified by mesalamine use or non-use.
Interventions
DRUGHMPL-004 low dose
HMPL-004, 400 mg (2 x 200 mg) t.i.d. (total of 1200 mg/day).
DRUGPlacebo
Matching dose of Placebo
DRUGHMPL-004 high dose
HMPL-004, 600 mg (3 x 200 mg) t.i.d. (total of 1800 mg/day).
Sponsors
Hutchison Medipharma Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have active confirmed mild to moderate ulcerative colitis
Exclusion criteria
* Diagnosed with Crohn's Disease or
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Clinical Response at Week 8 | 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Clinical Remission at Week 8 | 8 weeks | 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. |
| Number of Participants With Mucosal Healing at Week 8 | 8 weeks | 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. |
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 74 |
| 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). | 74 |
| Placebo Placebo, t.i.d. | 75 |
| Total | 223 |
Baseline characteristics
| Characteristic | Total | Low Dose HMPL-004 (1200 mg/Day) | Placebo | High Dose HMPL-004 (1800 mg/Day) |
|---|---|---|---|---|
| Age, Continuous | 44.87 Years STANDARD_DEVIATION 14.4 | 44.3 Years STANDARD_DEVIATION 14.5 | 44.68 Years STANDARD_DEVIATION 15.21 | 45.64 Years STANDARD_DEVIATION 13.61 |
| Sex: Female, Male Female | 101 Participants | 34 Participants | 34 Participants | 33 Participants |
| Sex: Female, Male Male | 122 Participants | 40 Participants | 41 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 74 | 0 / 75 |
| other Total, other adverse events | 45 / 75 | 39 / 74 | 45 / 75 |
| serious Total, serious adverse events | 2 / 75 | 2 / 74 | 2 / 75 |
Outcome results
Primary
Number of Participants With a Clinical Response at Week 8
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.
Time frame: 8 weeks
Population: Based on number of subjects with a non-missing value in each treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose HMPL-004 (1200 mg/Day) | Number of Participants With a Clinical Response at Week 8 | 33 Participants |
| High Dose HMPL-004 (1800 mg/Day) | Number of Participants With a Clinical Response at Week 8 | 45 Participants |
| Placebo | Number of Participants With a Clinical Response at Week 8 | 30 Participants |
Secondary
Number of Participants With a Clinical Remission at Week 8
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.
Time frame: 8 weeks
Population: Based on number of subjects with a non-missing value in each treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose HMPL-004 (1200 mg/Day) | Number of Participants With a Clinical Remission at Week 8 | 25 Participants |
| High Dose HMPL-004 (1800 mg/Day) | Number of Participants With a Clinical Remission at Week 8 | 28 Participants |
| Placebo | Number of Participants With a Clinical Remission at Week 8 | 19 Participants |
Secondary
Number of Participants With Mucosal Healing at Week 8
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.
Time frame: 8 weeks
Population: Based on number of subjects with a non-missing value in each treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose HMPL-004 (1200 mg/Day) | Number of Participants With Mucosal Healing at Week 8 | 28 Participants |
| High Dose HMPL-004 (1800 mg/Day) | Number of Participants With Mucosal Healing at Week 8 | 37 Participants |
| Placebo | Number of Participants With Mucosal Healing at Week 8 | 25 Participants |