| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Ulcerative colitis (UC) is a disease where inflammation develops in the large intestine (the colon and rectum). |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045365 |
| E.1.2 | Term | Ulcerative colitis |
| E.1.2 | System Organ Class | 100000004856 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The purpose of this trial is to determine the efficacy and safety of HMPL-004 given at 1800 mg/day as maintenance therapy in subjects with active mild to moderate UC who have achieved clinical remission or response through induction therapy. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 UC 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 5 ASA 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: abstinence, 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.
|
|
| E.4 | Principal exclusion criteria |
1) Subjects with intolerance or adverse reactions to mesalamine (or 5-ASA equivalent medications).
2) 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. Subjects with PSC (Primary Sclerosing Cholangitis) are excluded.
3) Severe disease with a UC modified Mayo Clinic score above 10 points at baseline.
4) Positive stool test for pathogens on sample taken within the 2 weeks prior to study entry (as applicable for the Open Label Phase).
5) Active Clostridium difficile (C. diff) infection.
6) Use of IBD related herbal supplements including supplements containing andrographis or the use of probiotics two weeks prior to study entry or during the study.
7) Toxic megacolon or toxic colitis.
8) Probable requirement for intestinal surgery within 12 weeks after the start of investigational product.
9) Receiving oral or rectal steroids within 1 month prior to study entry.
10) Receiving rectal mesalamine (or 5-ASA equivalent) within 1 week prior to study entry.
11) Receiving azathioprine, 6-mercaptopurine, methotrexate, tacrolimus, cyclosporine, or other immunosuppressive therapy at the time of screening or within the preceding 6 weeks.
12) Receiving anti-TNF-α agents such as infliximab, adalimumab, golimumab, or certolizumab pegol at the time of screening or within the preceding 8 weeks.
13) Receiving other investigational drugs or biologics within 1 month or five half–lives, whichever is longer.
14) Receiving antibiotics within 2 weeks of study entry.
15) Hemoglobin concentration <9 g/dl.
16) WBC below 3,000/cm3, or platelets below 100,000/cm3.
17) Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or alkaline phosphatase >2.5 upper limit of normal.
18) Serum creatinine >1.5 times upper limit of normal.
19) 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.
20) Chronic Hepatitis B or any history of Hepatitis C.
21) Previous colonic surgery except for simple polypectomy or appendectomy.
22) History of cancer within the last 5 years other than resected cutaneous basal and squamous cell carcinomas, and/or in situ cervical cancer.
23) Subjects with a history of or concurrent colonic dysplasia associated with UC, except those with completely excised sporadic colorectal polyps.
24) Women who are pregnant or breast feeding.
25) Subjects known to be seropositive for HIV, or who have had an AIDS defining illness, or a known immunodeficiency disorder.
26) History of alcohol or drug abuse that would interfere with the ability to be compliant with the study procedure.
27) Known allergy to plants of the Acanthaceae family.
28) Unwillingness to participate in the study.
29) 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 AEs
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the proportion of subjects who are in clinical remission after 52 weeks of maintenance treatment, following successful induction therapy to achieve clinical remission or clinical response. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Key Secondary End Points:
• The proportion of subjects who have maintained clinical remission after 52 weeks of maintenance treatment, following successful induction therapy to achieve clinical remission.
• The proportion of subjects who are in clinical response after 52 weeks of maintenance treatment, following successful induction therapy to achieve clinical remission or clinical response.
• The proportion of subjects who have maintained clinical response after 52 weeks of maintenance treatment, following successful induction therapy to achieve clinical response. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Bulgaria |
| Czech Republic |
| Hungary |
| Latvia |
| Lithuania |
| Poland |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| last visit of the Last Subject (LVLS) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 14 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
