A Phase III Trial of HMPL-004 in Patients With Mild to Moderate Active Ulcerative Colitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Hutchison Medipharma Limited
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited
ClinicalTrials.gov Identifier:
NCT01805791
First received: March 4, 2013
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

A placebo controlled study of two doses of HMPL-004 in patients 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.

The objective is to evaluate the efficacy and safety of HMPL-004 with mesalamine (mesalamine treatment failures). Efficacy will be measured by a comparison of the proportion of patients in each treatment group attaining clinical remission at Week 8 as compared to placebo.


Condition Intervention Phase
Ulcerative Colitis
Drug: HMPL-004 tablet
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Multi-Centre, Double-Blind, Placebo-Controlled Trial of HMPL-004 in Patients With Mild to Moderate Active Ulcerative Colitis

Resource links provided by NLM:


Further study details as provided by Hutchison Medipharma Limited:

Primary Outcome Measures:
  • The Efficacy of HMPL-004 in patients taking mesalamine as compared to placebo. [ Time Frame: After 8 weeks of treatment ] [ Designated as safety issue: Yes ]
    Patients will be evaluated for their change of disease activity after 8 weeks of treatment by means of a Modified Mayo Scoring system. Patients will be evaluated at week 8 for disease remission. For the current study, the definition of remission has been modified. The remission is defined as a total Mayo Score of < 2 points with no individual sub-score > 1 point AND rectal bleeding score = 0. For remission, the endoscopy will have no friability (meaning a score of 0 or 1). The endoscopy score has been modified such that any degree of friability will be scored as a 2 or greater. Safety will be assessed by the frequency, type and severity of Adverse Events during the 8 weeks of treatment for each dose of HMPL-004 used as compared to placebo.


Estimated Enrollment: 420
Study Start Date: March 2013
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo, oral tablets, three times a day
Drug: Placebo
Placebo tablets will be used in the placebo arm of the study.
Experimental: 1800 mg/day HMPL-004
1 600 mg HMPL-004 tablet, 2x400 mg placebo tablets taken 3 times a day
Drug: HMPL-004 tablet
Experimental: 2400 mg/day
2 x 400 mg HMPL tablets, 1 x 600 mg placebo tablet, taken 3 times per day
Drug: HMPL-004 tablet

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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 centrally read colonoscopy (within 2 weeks prior to randomization.
  • Minimum modified Mayo endoscopy score of >2 at the time of study colonoscopy.
  • Age ≥ 18 years.
  • Patients have no prior exposure to HMPL-004.
  • Have adequate renal, hepatic and bone marrow function (see exclusion criteria).
  • All fertile male and female subjects must agree to use one of the following types of contraception: abstinence, 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.
  • 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

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. Subjects with PSC (Primary Sclerosing Cholangitis) are excluded..
  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 Inflammatory Bowel Disease related herbal supplements including but not limited to 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-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.
  14. Receiving antibiotics within 2 weeks of study entry.
  15. Hemoglobin concentration < 9 g/dl.
  16. WBC below 3,000/cmm, or platelets below 100,000/cmm.
  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 or any history of Hepatitis C.
  21. Previous colonic surgery except for simple polypectomy or appendectomy. .
  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. Patients with a history of tuberculosis or exposure to tuberculosis, or a history of a chest X-ray suspicious for tuberculosis, unless confirmed to be PPD negative or latent tuberculosis that has been previously treated.
  27. History of alcohol or drug abuse that would interfere with the ability to be compliant with the study procedure.
  28. Known allergy to plants of the Acanthaceae family.
  29. Unwillingness to participate in the study.
  30. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01805791

Contacts
Contact: Gerald McPherson 512 301 7615 Gerald McPherson <GMcpherson@clinicalresearchmgt.com>

Locations
United States, Massachusetts
Clinical Research Management, Inc Recruiting
Agawam, Massachusetts, United States
Sponsors and Collaborators
Hutchison Medipharma Limited
  More Information

No publications provided

Responsible Party: Hutchison Medipharma Limited
ClinicalTrials.gov Identifier: NCT01805791     History of Changes
Other Study ID Numbers: HMPL-004-03
Study First Received: March 4, 2013
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Hutchison Medipharma Limited:
Ulcerative Colitis,
UC
Patients
active
mild
moderate

Additional relevant MeSH terms:
Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases

ClinicalTrials.gov processed this record on September 16, 2014