A Phase II, Randomized, Multi-Centre, Double-Blind, Placebo-Controlled Trial of HMPL-004 in Patients with Mild to Moderate Active Ulcerative Colitis with or without Mesalamine

• Register: EUCTR
• Last refreshed on: 11 September 2012
• Main ID: EUCTR2007-005166-12-DE
• Date of registration: 15/01/2008
• Prospective Registration: Yes
• Primary sponsor: Hutchison MediPharma Enterprises Limited
• Public title: A Phase II, Randomized, Multi-Centre, Double-Blind, Placebo-Controlled Trial of HMPL-004 in Patients with Mild to Moderate Active Ulcerative Colitis with or without Mesalamine
• Scientific title: A Phase II, Randomized, Multi-Centre, Double-Blind, Placebo-Controlled Trial of HMPL-004 in Patients with Mild to Moderate Active Ulcerative Colitis with or without Mesalamine
• Date of first enrolment: 29/07/2008
• Target sample size: 210
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-005166-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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-a 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

active mild to moderate ulcerative colitis defined as a Mayo clinical score of 4-10 points
MedDRA version: 9.1 Level: LLT Classification code 10066678 Term: Acute ulcerative colitis

Intervention(s)

Product Name: HMPL-004
Pharmaceutical Form: Capsule*
Current Sponsor code: HMPL-004
Other descriptive name: ANDROGRAPHIS PANICULATA (ethanol extract)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 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.

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.

Secondary Objective: • 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.

Secondary ID(s)

HMPL-004-US-02