HMPL-004 Maintenance Treatment in Subjects With Mild to Moderate Ulcerative Colitis
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: HMPL-004; Placebo
Intervention description: Remitters and responders from HMPL-004 Induction study and patients complete the 8-week Open Label Induction Phase will be given HMPL-004 orally three times per day with total daily dose of 1800 mg for 52 weeks.; Remitters and responders from HMPL-004 Induction study and patients complete the 8-week Open Label Induction Phase will be given Placebo orally three times per day with total daily dose of 1800 mg for 52 weeks.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      A study with an 8 week open label phase study followed by a year long placebo controlled
      maintenance phase in subjects with active mild to moderate ulcerative colitis (UC), with a
      modified Mayo Score 4-10 and an endoscopy subscore of 2-3, taking mesalamine (or equivalent)
      as a concomitant medication. Subjects are required to be in clinical remission or clinical
      response to enter the year long maintenance phase. This study will help evaluate if HMPL-004
      is effective in subjects maintaining clinical remission following successful induction
      therapy achieving clinical remission or clinical response.
    

Eligibility criteria:

        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.