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

NCT01805791 | Terminated Phase 3 Results

• 1 other identifier: HMPL-004-03
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis,; UC; Patients; active; mild; moderate

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects With a Clinical Remission at Week 8

  Clinical remission was defined as a total Mayo Score of ≤2 points with no individual sub-score \>1 point and rectal bleeding score = 0.

  8 weeks

Secondary Outcomes (2)

• The Proportion of Subjects With Clinical Response at Week 8

  8 weeks

• The Proportion of Subjects With Mucosal Healing at Week 8

  8 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo, oral tablets, three times a day

Drug: Placebo

HMPL-004 1800 mg/day

EXPERIMENTAL

1 600 mg HMPL-004 tablet, 2x400 mg placebo tablets taken 3 times a day

Drug: HMPL-004 1800 mg/day

HMPL-004 2400 mg/day

EXPERIMENTAL

2 x 400 mg HMPL tablets, 1 x 600 mg placebo tablet, taken 3 times per day

Drug: HMPL-004 2400 mg/day

Interventions

HMPL-004 1800 mg/day DRUG

Subjects randomized to the arm of HMPL-004 1800 mg/day will receive HMPL-004 600 mg TID (total dose 1800 mg/day) for 56 days (8 weeks).

Also known as: Chuan xinlian

HMPL-004 1800 mg/day

Placebo DRUG

Subjects randomized to the arm of Placebo will receive matching Placebo three times daily for 56 days (8 weeks).

Placebo

HMPL-004 2400 mg/day DRUG

Subjects randomized to the arm of HMPL-004 2400 mg/day will receive HMPL-004 800 mg TID (total dose 2400 mg/day) for 56 days (8 weeks).

Also known as: Chuan xinlian

HMPL-004 2400 mg/day

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Subjects with intolerance or adverse reactions to mesalamine (or equivalent medications).
• 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 Primary Sclerosing Cholangitis (PSC) are excluded..
• Severe disease with an ulcerative colitis modified Mayo Clinic score above 10 points at baseline.
• Positive stool test for pathogens for sample taken within the previous 2 weeks prior to study entry.
• Active Clostridium difficile (C. diff) infection.
• 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.
• Toxic megacolon or toxic colitis.
• Probable requirement for intestinal surgery within 12 weeks after the start of study medication.
• Receiving oral or rectal steroids within 1 month prior to study entry.
• Receiving rectal mesalamine within one week prior to study entry.
• Receiving azathioprine, 6-mercaptopurine, methotrexate, tacrolimus, cyclosporine, or other immunosuppressive therapy at the time of screening or within the preceding 6 weeks.
• Receiving anti-tumor necrosis factor-α agents such as infliximab, adalimumab, golimumab, or certolizumab pegol at the time of screening or within the preceding 8 weeks.
• Receiving other investigational drugs or biologics within 1 month or five half lives.

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (1)

Clinical Research Management, Inc

Agawam, Massachusetts, 01001, United States

Location

MeSH Terms

Conditions

Colitis, Ulcerative; Motor Activity; Lymphoma, Follicular

Interventions

Andrographis paniculata extract

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases; Behavior; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr. Rongjun Liu
• Organization: Hutchison MediPharma Ltd

rongjunl@hmplglobal.com

+86 21 2067 3203

Study Officials

• Rongjun Liu, MD

  Hutchison Medipharma Limited

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subjects were randomized according to a stratified blocked randomization schedule generated by an unblinded biostatistician. Stratification was by country/region and modified Mayo Score at screening using an interactive web-based response system (IWRS).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2013
• First Posted: March 6, 2013
• Study Start: March 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: January 2, 2020
• Results First Posted: January 2, 2020

Record last verified: 2018-07

Locations

US (1)