HMPL-004 Maintenance Treatment in Subjects With Mild to Moderate Ulcerative Colitis (NATRUL-4)

This is an interventional treatment trial for Ulcerative Colitis Read More

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 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.
2. 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.
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: 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.

Exclusion Criteria:

1. Subjects with intolerance 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 a Ulcerative Colitis 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.
5. Active clostridium difficile (C. diff) infection.
6. 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.
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 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-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.
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. White blood cell count (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.
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 Adverse Events.