Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis,, UC, Patients, active, mild, moderate
Brief summary
A placebo controlled study of two doses of HMPL-004 in patients with active mild to moderate ulcerative colitis (UC), with a modified Mayo Score 4-10 and an endoscopy subscore of 2-3, taking mesalamine (or equivalent) as a concomitant medication. The objective is to evaluate the efficacy and safety of HMPL-004 with mesalamine (mesalamine treatment failures). Efficacy will be measured by a comparison of the proportion of patients in each treatment group attaining clinical remission at Week 8 as compared to placebo.
Detailed description
This Phase III study of HMPL-004 was to enroll approximately 420 subjects with active mild to moderate ulcerative colitis (UC; modified Mayo Score 4-10 and endoscopy score of 2-3). The trial included male and female subjects aged 18 or older. Subjects were currently receiving ≥2.4 g/day mesalamine or equivalent, provided they had taken 5-aminosalicylate (ASA; i.e., mesalamine) at a dose ≥2.4 g/day for at least 6 weeks prior to randomization and were on a stable dosage for at least 2 weeks prior to entering the screening phase of the study. Qualifying subjects who entered into this study received 3 daily doses of oral HMPL 004 tablets or placebo for 56 days (8 weeks). There were 3 arms in this study consisting of placebo, HMPL-004 600 mg three times a day (TID) or 800 mg TID. Approximately 420 subjects were to be randomized 1:1:1 to one of these 3 arms, stratified by country/region in up to 150 clinical centers in North America, Europe, and Asia.
Interventions
DRUGHMPL-004 2400 mg/day
Subjects randomized to the arm of HMPL-004 2400 mg/day will receive HMPL-004 800 mg TID (total dose 2400 mg/day) for 56 days (8 weeks).
DRUGHMPL-004 1800 mg/day
Subjects randomized to the arm of HMPL-004 1800 mg/day will receive HMPL-004 600 mg TID (total dose 1800 mg/day) for 56 days (8 weeks).
DRUGPlacebo
Subjects randomized to the arm of Placebo will receive matching Placebo three times daily for 56 days (8 weeks).
Sponsors
Hutchison Medipharma Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Subjects were randomized according to a stratified blocked randomization schedule generated by an unblinded biostatistician. Stratification was by country/region and modified Mayo Score at screening using an interactive web-based response system (IWRS).
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients must be currently receiving mesalamine ≥ 2.4 g/day (or the equivalent) for at least 6 weeks prior to randomization and on a stable dosage for at least 2 weeks prior to entering the screening phase of the study to ensure a stable dose is established at least 2 weeks prior to the endoscopic procedures. * Have active mild to moderate ulcerative colitis defined by a modified Mayo Score 4-10, and with endoscopy score activity of 2-3 points confirmed by centrally read colonoscopy (within 2 weeks prior to randomization. * Minimum modified Mayo endoscopy score of \>2 at the time of study colonoscopy. * Age ≥ 18 years. * Patients have no prior exposure to HMPL-004. * Have adequate renal, hepatic and bone marrow function (see
Exclusion criteria
). * All fertile male and female subjects must agree to use one of the following types of contraception: abstinence, intrauterine device, implantable progesterone device, and progesterone intramuscular injection, oral contraceptive which has been started at least one month prior to visit one and continues for the duration of the trial, contraceptive patch, or condom with spermicide. * Show evidence of a personally signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With a Clinical Remission at Week 8 | 8 weeks | Clinical remission was defined as a total Mayo Score of ≤2 points with no individual sub-score \>1 point and rectal bleeding score = 0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects With Clinical Response at Week 8 | 8 weeks | 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. |
| The Proportion of Subjects With Mucosal Healing at Week 8 | 8 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 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). | 66 |
| 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 a day (total dose 1800 mg/day) for 56 days (8 weeks). | 67 |
| HMPL-004 2400 mg/Day 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). | 68 |
| Total | 201 |
Baseline characteristics
| Characteristic | Placebo | HMPL-004 1800 mg/Day | HMPL-004 2400 mg/Day | Total |
|---|---|---|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 16.32 | 43.9 years STANDARD_DEVIATION 15.07 | 40.6 years STANDARD_DEVIATION 12.33 | 43.2 years STANDARD_DEVIATION 14.7 |
| Current Smoker: Yes, No No | 60 Participants | 63 Participants | 67 Participants | 190 Participants |
| Current Smoker: Yes, No Yes | 6 Participants | 4 Participants | 1 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 9 Participants | 10 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 58 Participants | 58 Participants | 173 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height, Continuous | 172.21 cm STANDARD_DEVIATION 10.3 | 170.67 cm STANDARD_DEVIATION 9.54 | 170.28 cm STANDARD_DEVIATION 8.74 | 171.05 cm STANDARD_DEVIATION 9.53 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 9 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 62 Participants | 63 Participants | 55 Participants | 180 Participants |
| Sex: Female, Male Female | 23 Participants | 37 Participants | 33 Participants | 93 Participants |
| Sex: Female, Male Male | 43 Participants | 30 Participants | 35 Participants | 108 Participants |
| Weight, Continuous | 80.94 kg STANDARD_DEVIATION 16 | 79.77 kg STANDARD_DEVIATION 19.35 | 82.24 kg STANDARD_DEVIATION 21.42 | 80.99 kg STANDARD_DEVIATION 19.01 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 68 | 0 / 67 | 0 / 66 |
| other Total, other adverse events | 31 / 68 | 25 / 67 | 21 / 66 |
| serious Total, serious adverse events | 0 / 68 | 0 / 67 | 4 / 66 |
Outcome results
Primary
Percentage of Subjects With a Clinical Remission at Week 8
Clinical remission was defined as a total Mayo Score of ≤2 points with no individual sub-score \>1 point and rectal bleeding score = 0.
Time frame: 8 weeks
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HMPL-004 2400 mg/Day | Percentage of Subjects With a Clinical Remission at Week 8 | 9 Participants |
| HMPL-004 1800 mg/Day | Percentage of Subjects With a Clinical Remission at Week 8 | 7 Participants |
| Placebo | Percentage of Subjects With a Clinical Remission at Week 8 | 9 Participants |
Secondary
The Proportion of Subjects With Clinical Response at Week 8
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.
Time frame: 8 weeks
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HMPL-004 2400 mg/Day | The Proportion of Subjects With Clinical Response at Week 8 | 23 Participants |
| HMPL-004 1800 mg/Day | The Proportion of Subjects With Clinical Response at Week 8 | 19 Participants |
| Placebo | The Proportion of Subjects With Clinical Response at Week 8 | 16 Participants |
Secondary
The Proportion of Subjects With Mucosal Healing at Week 8
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.
Time frame: 8 weeks
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HMPL-004 2400 mg/Day | The Proportion of Subjects With Mucosal Healing at Week 8 | 13 Participants |
| HMPL-004 1800 mg/Day | The Proportion of Subjects With Mucosal Healing at Week 8 | 13 Participants |
| Placebo | The Proportion of Subjects With Mucosal Healing at Week 8 | 14 Participants |