Ulcerative ColitisPhase 3NATRUL-4NCT01882764
HMPL-004 Maintenance Treatment in Subjects With Mild to Moderate Ulcerative Colitis
A Phase 3 study testing HMPL-004 in people with Ulcerative Colitis, run by Hutchison Medipharma Limited at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- HMPL-004
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to Oct 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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.
- Have adequate renal, hepatic and bone marrow function (see exclusion criteria).
- Age ≥ 18 years
- 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.
- 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.
Who cannot join
- Subjects with intolerance to mesalamine (or equivalent medications).
- Diagnosed with Crohn's disease or with lesions such as fistulas or granulomas on biopsy noted either in history or at baseline endoscope, which would be suspicious for Crohn's disease, or with a diagnosis of indeterminate colitis.
- Severe disease with a Ulcerative Colitis modified Mayo Clinic score above 10 points at baseline.
- Positive stool test for pathogens on sample taken within the 2 weeks prior to study entry.
- Active clostridium difficile (C. diff) infection.
- Use of Inflammatory Bowel Disease related herbal supplements including supplements containing andrographis or the use of probiotics two weeks prior to study entry or during the study.
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- Toxic megacolon or toxic colitis.
- Probable requirement for intestinal surgery within 12 weeks after the start of investigational product.
- Receiving oral or rectal steroids within 1 month prior to study entry.
- Receiving rectal mesalamine within 1 week prior to study entry.
- Receiving azathioprine, 6-mercaptopurine, methotrexate, tacrolimus, cyclosporine, or other immunosuppressive therapy at the time of screening or within the preceding 6 weeks.
- Receiving anti-tumor necrosis factor-α (TNF-α)agents such as infliximab, adalimumab, golimumab, or certolizumab pegol at the time of screening or within the preceding 8 weeks.
- Receiving other investigational drugs or biologics within 1 month or five half-lives, whichever is longer.
- Receiving antibiotics within 2 weeks of study entry.
- Hemoglobin concentration <9 g/dl.
- White blood cell count (WBC) below 3,000/cm3, or platelets below 100,000/cm3.
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or alkaline phosphatase >2.5 upper limit of normal.
- Serum creatinine >1.5 times upper limit of normal.
- Significant concurrent medical diseases including: active peptic ulcer disease; uncompensated congestive heart disease; myocardial infarction within the last 12 months; unstable angina pectoris; uncontrolled hypertension; and pulmonary disease requiring oxygen therapy.
- Chronic Hepatitis B or any history of Hepatitis C.
- Previous colonic surgery except for simple polypectomy.
- History of cancer within the last 5 years other than resected cutaneous basal and squamous cell carcinomas, and/or in situ cervical cancer.
- Subjects with a history of or concurrent colonic dysplasia associated with UC, except those with completely excised sporadic colorectal polyps.
- Women who are pregnant or breast feeding.
- Subjects known to be seropositive for HIV, or who have had an AIDS defining illness, or a known immunodeficiency disorder.
- History of alcohol or drug abuse that would interfere with the ability to be compliant with the study procedure.
- Known allergy to plants of the Acanthaceae family.
- Unwillingness to participate in the study.
- Any underlying medical condition that in the Investigator's opinion will make the administration of study drug hazardous to the subject or would obscure the interpretation of Adverse Events.
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical Research Management, Inc.
Agawam, Massachusetts, 01001
About this study
Official title: A Phase III Double Blind, Multi-Center Placebo Controlled Maintenance Trial of HMPL-004 in Subjects With Mild to Moderate Ulcerative Colitis With Clinical Remission or Response From Induction Therapy. (NATRUL-4)
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.
Read the 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.
- Conditions
- Ulcerative Colitis
- Being tested
- HMPL-004, Placebo
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMPL-004Drug
Also called Chuan xinlian
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| HMPL-004 1800 mg/day | Experimental | 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. Receives: Drug: HMPL-004 |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionOct 2014
- Study completionOct 2014
Why it stopped: Futility interim analysis of the Induction Study HMPL-004-03.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchison Medipharma Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Nutrition Science Partners Limited
- Responsible party
- Sponsor
- Investigators
- Liu Rongjun, Dr., Study director, Hutchison Medipharma Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01882764
- Sponsor's protocol ID
- HMPL-004-04
- Acronym
- NATRUL-4
- Status last verified
- Feb 2019
- First submitted
- 17 Jun 2013
- Last updated
- 13 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Double Blind, Multi-Center Placebo Controlled Maintenance Trial of HMPL-004 in Subjects With Mild to Moderate Ulcerative Colitis With Clinical Remission or Response From Induction Therapy. (NATRUL-4)
- ClinicalTrials.gov ID
- NCT01882764
- Acronym / sponsor ID
- NATRUL-4 / HMPL-004-04
- Conditions
- Ulcerative Colitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Futility interim analysis of the Induction Study HMPL-004-03.
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Hutchison Medipharma LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Nutrition Science Partners Limited
- Study start
- Jun 2013
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 20 Jun 2013 (estimated)
- Results
- Posted 13 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HMPL-004 1800 mg/day | Experimental | Drug: HMPL-004Subjects 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. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
- 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.
- Have adequate renal, hepatic and bone marrow function (see exclusion criteria).
- Age ≥ 18 years
- 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.
Key exclusion criteria (29 listed)
- Subjects with intolerance to mesalamine (or equivalent medications).
- Diagnosed with Crohn's disease or with lesions such as fistulas or granulomas on biopsy noted either in history or at baseline endoscope, which would be suspicious for Crohn's disease, or with a diagnosis of indeterminate colitis.
- Severe disease with a Ulcerative Colitis modified Mayo Clinic score above 10 points at baseline.
- Positive stool test for pathogens on sample taken within the 2 weeks prior to study entry.
- Active clostridium difficile (C. diff) infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HMPL-004Also: Chuan xinlianRemitters 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. | Drug | HMPL-004 1800 mg/day |
| PlaceboRemitters 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. | Drug | Placebo |
Primary outcome
The Proportion of Subjects Achieving Clinical Remission
Time frame: 52 weeks
Clinical remission is defined as a modified Mayo Score ≤2 along with no individual score >1 AND rectal bleeding score = 0.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Liu Rongjun, Dr. study director
Hutchison Medipharma Limited
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing HMPL-004 in people with Ulcerative Colitis, run by Hutchison Medipharma Limited at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Proportion of Subjects Achieving Clinical Remission (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2020; AzTrials last refreshed its copy on 7 Nov 2026.