E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
active mild to moderate ulcerative colitis defined as a Mayo clinical score of 4-10 points |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066678 |
E.1.2 | Term | Acute ulcerative colitis |
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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 primary objective of this study is to evaluate the efficacy of HMPL-004 given at 1200 mg/day, or 1800 mg/day in three divided doses, compared with placebo, in patients with mild to moderate ulcerative colitis as defined by the percent of patients in each treatment group attaining 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. |
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E.2.2 | Secondary objectives of the trial |
• To determine if there is a significant difference in the proportion of patients in each treatment group with a clinical remission at week 8. • To determine if there is a significant difference in the proportion of patients in each treatment group with a significant decrease from baseline in the Mayo endoscopy sub score ≥ 1 AND absolute score ≤ 1 (mucosal healing). • To determine the time to response • To compare the decrease in the mean and median Mayo Score at baseline and week 8 in each treatment group. • To determine if there is a significant difference in any of the above efficacy measurements in patients with/without Mesalamine used as a concomitant medication. • To assess if there is a dose response difference in any of the above efficacy measurements in patients with two dose level of the HMPL-004. • To assess safety in patients
Exploratory Objective: To determine normalization of the CRP values in those patients entering the study with elevated values. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Have active confirmed mild to moderate ulcerative colitis defined by a Mayo score 4-10, and with activity confirmed by study colonoscopy or sigmoidoscopy within 2 weeks prior to study entry. 2) Minimum Mayo endoscopy score of ≥1 at the time of study colonoscopy or sigmoidoscopy. 3) Age ≥ 18 years 4) Have adequate renal, hepatic and bone marrow function (see exclusion criteria). 5) Female patients must be of non-childbearing potential defined as meeting at least one of the following criteria: • Age ≥ 50 years and naturally amenorrhoeic for ≥ 1 year*. • Premature ovarian failure confirmed by a specialist gynaecologist. • Previous bilateral salpingo-oophorectomy, or hysterectomy. • XY genotype, Turner’s syndrome, uterine agenesis. *Amenorrhoea following cancer therapy does not rule out childbearing potential. Fertile male and their partners 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, contraceptive patch, or condom with spermicide during the study participation and within 3 months thereafter. 6) 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 7) May be on Mesalamine (or equivalent medications sulfasalazine, balsalazide, olsalazine) if they have been on it for at least 4 weeks prior to randomization, and the dose has been stable for ≥ 2 weeks prior to randomization
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E.4 | Principal exclusion criteria |
1) 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 indeterminant colitis; 2) Severe disease with an ulcerative colitis Mayo Clinical score above 10 points at baseline. 3) Positive stool test for pathogens on any one of three samples taken within the previous 2 weeks prior to study entry. 4) Toxic megacolon or toxic colitis 5) Probable requirement for intestinal surgery within 12 weeks after the start of study medication 6) Receiving oral or rectal steroids within 1 month prior to study entry. 7) Receiving rectal Mesalamine within one week prior to study entry 8) Receiving Azathioprine, 6 MP, or other immunosuppressive therapy including anti-TNF-α agents at the time of screening or within the preceding 6 weeks. 9) Receiving other investigational drugs or biologics within 1 month. 10) Receiving antibiotics within 2 week of study entry 11) Hemoglobin concentration < 9 g/dl 12) WBC below 3,000/cmm, or platelets below 100,000/cmm 13) SGOT, SGPT, alkaline phosphatase >2.5 upper limit of normal 14) Serum creatinine >1.5 times upper limit of normal 15) 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; pulmonary disease requiring oxygen therapy. 16) Chronic active Hepatitis B within the last 1 year (unless shown at the time of study entry to be Hepatitis B antigen negative) or any history of Hepatitis C. 17) Previous colonic surgery except for simple polypectomy. 18) History of cancer within the last 5 years other than resected cutaneous basal and squamous cell carcinomas, in situ cervical cancer and surgically removed colon polyps. 19) Women who are pregnant or breast feeding ; 20) Patients known to be seropositive for HIV, or who have had an AIDS defining illness, or a known immunodeficiency disorder 21) Patients with a history of tuberculosis or exposure to tuberculosis, or a history of a chest X ray suspicious for tuberculosis, unless shown to be PPD negative. 22) History of alcohol or drug abuse that would interfere with the ability to be compliant with the study procedure; 23) Known allergy to plants of the Acanthaceae family; 24) Unwillingness to participate in the study; 25) Any underlying medical condition that in the Investigator’s opinion will make the administration of study drug hazardous to the patient or would obscure the interpretation of adverse events.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients in each treatment group with a decrease in Mayo Score from baseline ≥ 3 AND ≥ 30% decrease in the Mayo score, along with either a decrease in rectal bleeding score ≥ 1 OR absolute rectal bleeding score ≤ 1 after 8 weeks of treatment with HMPL-004 given orally three times/day. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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.8.3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 18 |
E.8.9.2 | In all countries concerned by the trial days | 0 |