A Placebo Controlled Trial of HMPL-004 in Patients with Mild to Moderate Active Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2013-002116-27-HU
• Date of registration: 24/07/2013
• Prospective Registration: Yes
• Primary sponsor: Nutrition Science Partners Limited
• Public title: A Placebo Controlled Trial of HMPL-004 in Patients with Mild to Moderate Active Ulcerative Colitis
• Scientific title: A Phase III, Randomized, Multi-Centre, Double-Blind, Placebo-Controlled Trial of HMPL-004 in Patients with Mild to Moderate Active Ulcerative Colitis (NATRUL-3)
• Date of first enrolment: 24/10/2013
• Target sample size: 420
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002116-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Bulgaria, Czech Republic, Hungary, Korea, Republic of, Latvia, Lithuania, Poland, Ukraine, United States

Contacts

• Name: Clinical Development
• Affiliation: Nutrition Science Partners Limited

• Name: Clinical Development
• Affiliation: Nutrition Science Partners Limited

Key inclusion & exclusion criteria

Inclusion criteria:
1) Patients 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.
2) Have active mild to moderate ulcerative colitis defined by a modified Mayo Score 4-10, and with endoscopy score activity of 2-3 points confirmed by a full colonoscopy within 2 weeks prior to randomization. Activity can be in any of the 5 colon segments.
3) Age = 18 years.
4) Patients have no prior exposure to HMPL-004.
5) Have adequate renal, hepatic and bone marrow function (see exclusion criteria).
6) All fertile male and female subjects must agree to use one of the following types of contraception: intrauterine device, implantable progesterone device, and 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.
7) 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
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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion criteria:
1) Subjects with intolerance or adverse reactions to mesalamine (or 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.
3) Severe disease with an ulcerative colitis modified Mayo Clinic score above 10 points at baseline.
4) Positive stool test for pathogens for sample taken within the previous 2 weeks prior to study entry.
5) Active Clostridium difficile (C. diff) infection.
6) Use of IBD related herbal supplements including supplements containing andrographis and 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 study medication.
9) Receiving oral or rectal steroids within 1 month prior to study entry.
10) Receiving rectal mesalamine within one 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-a 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.
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) SGOT, SGPT, 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; pulmonary disease requiring oxygen therapy.
20) Chronic Hepatitis B any history of Hepatitis C.
21) Previous colonic surgery except for simple polypectomy.
22) History of cancer within the last 5 years other than resected cutaneous basal and squamous cell carcinomas, and in situ cervical cancer.
23) Patients 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) Patients 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 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

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Ulcerative Colitis (UC)
MedDRA version: 17.0 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Code: HMPL-004
Pharmaceutical Form: Tablet
CAS Number: 8000051-24-3
Current Sponsor code: HMPL-004
Other descriptive name: ANDROGRAPHIS PANICULATA
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 2400-
CAS Number: 5508-58-7
Other descriptive name: AND (Andrographolide)
CAS Number: 27215-14-1
Other descriptive name: NAND (Neoandrographolide)
CAS Number: 4176-97-0
Other descriptive name: DAND (14-Deoxyandrographolide)
CAS Number: 42895-58-9
Other descriptive name: DDAND (14-deoxy-11,12-didehydroandrographolide)
CAS Number: 327-97-9
Other descriptive name: CLA (Chlorogenic acid)
CAS Number: 29741-09-1
Other descriptive name: AODG (Apigenin-7-O-glucuronide)
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: Secondary endpoints of this study include clinical response and mucosal healing. In this study, each of the colon segments (cecum/ascending, transverse, descending, sigmoid, and rectum) will be reviewed endoscopically and centrally evaluated at the beginning of the study (screening phase) and at end of study to observe the extent of colonic involvement before and after treatment.

Timepoint(s) of evaluation of this end point: Week 8

Primary end point(s): Clinical remission will be measured by the modified Mayo Score (also known as the Clinical Mayo Score or the disease activity index [DAI]), which serves as the current leading measurement of disease and is used in many of the ulcerative colitis trials.

Main Objective: The primary objective of this study is to evaluate the efficacy as defined by the percentage of patients attaining clinical remission following 8 weeks of induction treatment of HMPL-004 given at a dosing level of either 1800 mg/day or 2400 mg/day as compared with placebo in patients with mild to moderate ulcerative colitis that currently have a sub-optimal response to their current regimen of mesalamine.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1) Week 8
2) Week 8
3) Weeks 2, 4, 6, 8
4) Week 8

Secondary end point(s): 1) The proportion of patients with clinical response at Week 8 in each HMPL-004 group compared with the placebo group.
2)The proportion of patients with mucosal healing at Week 8 in each HMPL-004 group compared with the placebo group.
3) To determine the time to response as measured by the first assessment at which there was a significant difference between the proportion of patients in either treatment group and placebo who showed a decrease in the partial Mayo Score of = 2 as compared to baseline at Weeks 2, 4, 6 and 8.
4) Decrease in the mean and median modified Mayo Score at baseline and Week 8 in each treatment group.

Secondary ID(s)

2013-002116-27-LV

HMPL-004-03

NCT01805791

Source(s) of Monetary Support

Nutrition Science Partners Limited