Ulcerative Colitis
Conditions
Brief summary
A study with an 8 week open label phase study followed by a year long placebo controlled maintenance phase in subjects 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. Subjects are required to be in clinical remission or clinical response to enter the year long maintenance phase. This study will help evaluate if HMPL-004 is effective in subjects maintaining clinical remission following successful induction therapy achieving clinical remission or clinical response.
Detailed description
A two-phase multi-center study with an open label 8-week induction phase and a randomized, double-blind, placebo controlled maintenance phase to evaluate the efficacy and safety of HMPL-004 for a 52-week maintenance therapy in adults with mild to moderate UC and who have demonstrated a sub-optimal response to mesalamine treatment. The study participants will consist of subjects who have completed either the HMPL-004-03 or HMPL-004-05 induction study, complemented by the enrollment of additional subjects in the open label induction phase who meet the entry criteria of this study. . Subjects entering this maintenance study from one of the HMPL-004 induction studies will have their modified Mayo baseline score from that study as their baseline score for this study. All subjects enrolled in the open label induction phase of the study will be re-evaluated for clinical response and remission after the 8-week open label 2400 mg HMPL-004 treatment period. Clinical responders and remitters will be randomized 2:1 (HMPL-004: placebo) to HMPL-004 1800 mg/day or placebo group for the 52-week maintenance phase of the study.
Interventions
DRUGHMPL-004
Remitters and responders from HMPL-004 Induction study and patients complete the 8-week Open Label Induction Phase will be given HMPL-004 orally three times per day with total daily dose of 1800 mg for 52 weeks.
DRUGPlacebo
Remitters and responders from HMPL-004 Induction study and patients complete the 8-week Open Label Induction Phase will be given Placebo orally three times per day with total daily dose of 1800 mg for 52 weeks.
Sponsors
Nutrition Science Partners Limited
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
1. Completion of induction study HMPL-004-03 or HMPL-004-05 and achieving clinical remission or response with no disruption of study treatment in the transition to HMPL-004-04, or, for the open label induction phase of the study: have active mild to moderate Ulcerative Colitis defined by a modified Mayo Score of 4 to 10 and with endoscopy score activity of 2-3 points confirmed by a full colonoscopy within 2 weeks prior to study. 2. Subjects 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. 3. Have adequate renal, hepatic and bone marrow function (see
Exclusion criteria
). 4. Age ≥ 18 years 5. All fertile male and female subjects must agree to use one of the following types of contraception: intrauterine device, implantable progesterone device, 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. 6. Show evidence of a personally signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects Achieving Clinical Remission | 52 weeks | Clinical remission is defined as a modified Mayo Score ≤2 along with no individual score \>1 AND rectal bleeding score = 0. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HMPL-004 1800 mg/Day Subjects qualifying for entry into the Maintenance Phase of the study were randomized to take an oral dose of HMPL-004 (600 mg TID; total dose 1800 mg/day) daily, for 52 weeks.
Those subjects who demonstrated clinical remission or response after completing the HMPL-004-03 Induction Study, or after completing the Open Label Phase of this study, were eligible for enrollment in the Maintenance Phase of this study.
HMPL-004: Remitters and responders from HMPL-004 Induction study and patients complete the 8-week Open Label Induction Phase will be given HMPL-004 orally three times per day with total daily dose of 1800 mg for 52 weeks. | 46 |
| Placebo Subjects qualifying for entry into the Maintenance Phase of the study were randomized to take an oral dose of Placebo tablets TID, daily, for 52 weeks.
Those subjects who demonstrated clinical remission or response after completing the HMPL-004-03 Induction Study, or after completing the Open Label Phase of this study, were eligible for enrollment in the Maintenance Phase of this study.
Placebo: Remitters and responders from HMPL-004 Induction study and patients complete the 8-week Open Label Induction Phase will be given Placebo orally three times per day with total daily dose of 1800 mg for 52 weeks. | 19 |
| Total | 65 |
Baseline characteristics
| Characteristic | HMPL-004 1800 mg/Day | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 41.5 years STANDARD_DEVIATION 14.01 | 47.8 years STANDARD_DEVIATION 15.64 | 43.4 years STANDARD_DEVIATION 14.67 |
| Current Smoker: Yes, No No | 43 Participants | 18 Participants | 61 Participants |
| Current Smoker: Yes, No Yes | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 16 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 170.87 cm STANDARD_DEVIATION 9.64 | 173.33 cm STANDARD_DEVIATION 7.99 | 171.59 cm STANDARD_DEVIATION 9.2 |
| Race Asian | 1 Participants | 0 Participants | 1 Participants |
| Race Black | 2 Participants | 1 Participants | 3 Participants |
| Race Other | 2 Participants | 0 Participants | 2 Participants |
| Race White | 41 Participants | 18 Participants | 59 Participants |
| Region of Enrollment Bulgaria | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Czechia | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Latvia | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Lithuania | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Poland | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 38 Participants | 18 Participants | 56 Participants |
| Sex: Female, Male Female | 21 Participants | 7 Participants | 28 Participants |
| Sex: Female, Male Male | 25 Participants | 12 Participants | 37 Participants |
| Weight | 80.65 kg STANDARD_DEVIATION 16.7 | 85.99 kg STANDARD_DEVIATION 24.29 | 82.21 kg STANDARD_DEVIATION 19.18 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 19 |
| other Total, other adverse events | 11 / 46 | 4 / 19 |
| serious Total, serious adverse events | 0 / 46 | 0 / 19 |
Outcome results
Primary
The Proportion of Subjects Achieving Clinical Remission
Clinical remission is defined as a modified Mayo Score ≤2 along with no individual score \>1 AND rectal bleeding score = 0.
Time frame: 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HMPL-004 1800 mg/Day | The Proportion of Subjects Achieving Clinical Remission | 0 Participants |
| Placebo | The Proportion of Subjects Achieving Clinical Remission | 0 Participants |