Study of E6011 in Japanese Subjects With Primary Biliary Cholangitis Inadequately Responding to Ursodeoxycholic Acid

January 3, 2019 updated by: EA Pharma Co., Ltd.

A Clinical Phase 2 Study of E6011 in Japanese Subjects With Primary Biliary Cholangitis Inadequately Responding to Ursodeoxycholic Acid

This study is a placebo-controlled, randomized, double-blind, multicenter, parallel-group comparison study in primary biliary cholangitis participants inadequately responding to ursodeoxycholic acid.

Study Overview

Status

Terminated

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Fukuoka, Japan
        • EA Pharma Trial Site #1
      • Fukuoka, Japan
        • EA Pharma Trial Site #2
      • Fukushima, Japan
        • EA Pharma Trial Site
      • Hiroshima, Japan
        • EA Pharma Trial Site #1
      • Hiroshima, Japan
        • EA Pharma Trial Site #2
      • Kagoshima, Japan
        • EA Pharma Trial Site
      • Kumamoto, Japan
        • EA Pharma Trial Site
      • Kyoto, Japan
        • EA Pharma Trial Site
      • Niigata, Japan
        • EA Pharma Trial Site
      • Okayama, Japan
        • EA Pharma Trial Site
      • Osaka, Japan
        • EA Pharma Trial Site
      • Saga, Japan
        • EA Pharma Trial Site
      • Yamagata, Japan
        • EA Pharma Trial Site
    • Aichi
      • Nagoya, Aichi, Japan
        • EA Pharma Trial Site
    • Chiba
      • Matsudo, Chiba, Japan
        • EA Pharma Trial Site
    • Ehime
      • Touon, Ehime, Japan
        • EA Pharma Trial Site
    • Fukui
      • Yoshida, Fukui, Japan
        • EA Pharma Trial Site
    • Fukuoka
      • Kurume, Fukuoka, Japan
        • EA Pharma Trial Site
    • Gunma
      • Maebashi, Gunma, Japan
        • EA Pharma Trial Site
    • Hokkaido
      • Sapporo, Hokkaido, Japan
        • EA Pharma Trial Site #1
      • Sapporo, Hokkaido, Japan
        • EA Pharma Trial Site #2
    • Hyogo
      • Kobe, Hyogo, Japan
        • EA Pharma Trial Site
      • Nishinomiya, Hyogo, Japan
        • EA Pharma Trial Site
    • Ibaraki
      • Inashiki, Ibaraki, Japan
        • EA Pharma Trial Site
    • Iwate
      • Morioka, Iwate, Japan
        • EA Pharma Trial Site
    • Kagawa
      • Kita, Kagawa, Japan
        • EA Pharma Trial Site
      • Takamatsu, Kagawa, Japan
        • EA Pharma Trial Site
    • Kanagawa
      • Yokohama, Kanagawa, Japan
        • EA Pharma Trial Site #1
      • Yokohama, Kanagawa, Japan
        • EA Pharma Trial Site #2
    • Miyagi
      • Sendai, Miyagi, Japan
        • EA Pharma Trial Site
    • Nagano
      • Matsumoto, Nagano, Japan
        • EA Pharma Trial Site
    • Nagasaki
      • Oomura, Nagasaki, Japan
        • EA Pharma Trial Site
    • Nara
      • Kashihara, Nara, Japan
        • EA Pharma Trial Site
    • Okinawa
      • Nakagami, Okinawa, Japan
        • EA Pharma Trial Site
    • Osaka
      • Hirakata, Osaka, Japan
        • EA Pharma Trial Site
      • Suita, Osaka, Japan
        • EA Pharma Trial Site #1
      • Suita, Osaka, Japan
        • EA Pharma Trial Site #2
    • Saitama
      • Ageo, Saitama, Japan
        • EA Pharma Trial Site
      • Iruma, Saitama, Japan
        • EA Pharma Trial Site
    • Tochigi
      • Shimotsuga, Tochigi, Japan
        • EA Pharma Trial Site
    • Tokyo
      • Bunkyo, Tokyo, Japan
        • EA Pharma Trial Site
      • Itabashi, Tokyo, Japan
        • EA Pharma Trial Site
      • Minato, Tokyo, Japan
        • EA Pharma Trial Site #1
      • Minato, Tokyo, Japan
        • EA Pharma Trial Site #2
      • Musashino, Tokyo, Japan
        • EA Pharma Trial Site
      • Shinjuku, Tokyo, Japan
        • EA Pharma Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 72 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosed with primary biliary cholangitis corresponding to one of the following criteria:

    • Histologically confirmed chronic non-suppurative destructive cholangitis (CNSDC) with laboratory findings compatible with primary biliary cholangitis (PBC)
    • Positivity for antimitochondrial antibodies (AMAs) with histological findings compatible with PBC but in the absence of characteristic histological findings of CNSDC
    • No histological findings available, but positivity for AMAs as well as clinical findings and a course indicative of typical cholestatic PBC
  • Aged ≥20 and <75 years old at the time of informed consent
  • Taking stable dose of ursodeoxycholic acid for at least 6 months (≥600 milligrams [mg]/day) prior to Screening
  • Screening and Week 0 alkaline phosphatase (ALP) values between 1.67 and 10 times the upper limit of normal
  • Outpatient
  • Has voluntarily consented, in writing, to participate in this study, and is able to comply with all aspects of the protocol

Exclusion Criteria:

  • Received the following drugs within 12 weeks before starting the study treatment:

    • Drugs that suppose the efficacy to PBC:

      o azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, penicillamine, fibrates, and other systemic corticosteroids

    • Potentially hepatotoxic drugs o methyl-dopa, sodium valproic acid, and isoniazide
  • History or current condition of hepatic decompensation with variceal bleeds, encephalopathy ≥ grade 2 and poorly controlled ascites, and history of liver transplantation
  • History or current condition of other concomitant liver diseases including hepatitis due to hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, primary sclerosing cholangitis, alcoholic liver disease (including liver cirrhosis), autoimmune liver disease requiring the treatment of systemic corticosteroids or biopsy proven non-alcoholic steatohepatitis (NASH)
  • History or current clinical condition of malignant tumor, lymphoma, leukemia, or lymphoproliferative disease, except for skin carcinoma (epithelial carcinoma or basal cell carcinoma) and cervix carcinoma which has completely excised and without metastasis or recurrence for more than 5 years before informed consent
  • Immunodeficiency or history of human immunodeficiency virus (HIV) infection
  • Infection requiring hospitalization or intravenous administration of antibiotics or disease requiring administration of antivirus drugs (eg, herpes zoster) within 4 weeks before starting the study treatment
  • History of tuberculosis or current complication of active tuberculosis
  • Positive tuberculosis test (QuantiFERON®TB Gold Test or T-SPOT®.TB Test) at Screening
  • History of clinically important vasculitis
  • History of severe allergy (shock or anaphylactoid symptoms)
  • Complication of uncontrolled disorders such as acute cardiac infarction, unstable angina, brain infarct, or symptomatic intracerebral hemorrhage
  • Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, or renal disease) that could affect the participant's safety or interfere with the study assessments in the opinion of the investigator or subinvestigator
  • Tested positive for any of the following at Screening: HIV, hepatitis B surface (HBs) antigen, HBs antibody, hepatitis B core (HBc) antibody, HBV deoxyribonucleic acid (DNA), HCV antibody, human T-lymphotropic virus type 1 (HTLV-1) antibody, or syphilis
  • Demonstrated prolonged QT interval corrected using Fridericia's formula (QTcF) interval (>450 milliseconds [ms]) in repeated electrocardiogram examinations
  • Received immunoglobulin preparations or blood products within 24 weeks before starting the study treatment
  • Received a live vaccine within 12 weeks before starting the study treatment, or is planning to receive
  • Females who are, or may be pregnant, who are breastfeeding, who wish to become pregnant during the study period, and females or their partners who do not wish to use reliable contraceptive measures.
  • Scheduled for surgery before Week 64
  • Has been treated with investigational drugs in other E6011 study
  • Currently enrolled in another clinical study, including the follow-up
  • Used any investigational drug within 28 days (or 5× the half-life, whichever is longer) before informed consent
  • Judged to be ineligible to participate in this study by the investigator or sub-investigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: low-dose, high-frequency E6011; high-dose, low-frequency E6011
Participants will receive low-dose E6011 at a relatively higher frequency up to approximately Week 12. Participants will then receive high-dose E6011 at a relatively lower frequency from Week 12 to Week 64.
Intravenous administration
Experimental: low-dose, high-frequency E6011; low-dose, low-frequency E6011
Participants will receive low-dose E6011 at a relatively higher frequency up to approximately Week 12. Participants will then receive low-dose E6011 at a relatively lower frequency from Week 12 to Week 64.
Intravenous administration
Experimental: high-dose, low-frequency E6011; high-dose, low-frequency E6011
Participants will receive high-dose E6011 at a relatively lower frequency up to approximately Week 12. Participants will then receive high-dose E6011 at a relatively lower frequency from Week 12 to Week 64.
Intravenous administration
Experimental: high-dose, low-frequency E6011; low-dose, low-frequency E6011
Participants will receive high-dose E6011 at a relatively lower frequency up to approximately Week 12. Participants will then receive low-dose E6011 at a relatively lower frequency from Week 12 to Week 64.
Intravenous administration
Experimental: low-dose, low-frequency E6011; high-dose, low-frequency E6011
Participants will receive low-dose E6011 at a relatively lower frequency up to approximately Week 12. Participants will then receive high-dose E6011 at a relatively lower frequency from Week 12 to Week 64.
Intravenous administration
Experimental: low-dose, low-frequency E6011; low-dose, low-frequency E6011
Participants will receive low-dose E6011 at a relatively lower frequency up to approximately Week 12. Participants will then receive low-dose E6011 at a relatively lower frequency from Week 12 to Week 64.
Intravenous administration
Experimental: Placebo; high-dose, low-frequency E6011
Participants will receive placebo up to approximately Week 12. Participants will then receive high-dose E6011 at a relatively lower frequency from Week 12 to Week 64.
Intravenous administration
Intravenous administration
Experimental: Placebo; low-dose, low-frequency E6011
Participants will receive placebo up to approximately Week 12. Participants will then receive low-dose E6011 at a relatively lower frequency from Week 12 to Week 64.
Intravenous administration
Intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of change from Baseline in serum alkaline phosphatase (ALP) values at Week 12
Time Frame: Baseline; Week 12
This assessment will be conducted as a measure of efficacy.
Baseline; Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with a decrease in ALP response rates of 15%, 20%, and 40% from Baseline
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Number of participants with an ALP value less than 1.67 times the upper limit normal and a total bilirubin value within normal limits and a greater than or equal to 15% decrease in ALP from Baseline
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean values of serum ALP, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean values of gamma-guanosine-5'-triphosphate (γGTP) at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean values of serum total bilirubin and direct bilirubin at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean values of serum total bile acids at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean values of serum albumin at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean change from Baseline in serum ALP, AST, and ALT at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean change from Baseline in serum γGTP at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean change from Baseline in serum total bilirubin and direct bilirubin at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean change from Baseline in serum total bile acids at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean change from Baseline in serum albumin at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean rate of change from Baseline in serum ALP, AST, and ALT at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean rate of change from Baseline in serum γGTP at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean rate of change from Baseline in serum total bilirubin and direct bilirubin at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean rate of change from Baseline in serum total bile acids at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean rate of change from Baseline in serum albumin at each visit
Time Frame: Baseline; up to Week 64
This assessment will be conducted as a measure of efficacy.
Baseline; up to Week 64
Mean change from Baseline in individual domain and total primary biliary cholangitis (PBC) version Child-Pugh scores
Time Frame: Screening; up to Week 64
The Child-Pugh classification is used to assess the prognosis of chronic liver disease. The score employs five clinical measures of liver disease. Each measure is scored from 1 to 3, with 3 indicating most severe derangement. The total score ranges from 5 to 15 and is a sum of the individual domain scores. A higher score indicates a worse prognosis.
Screening; up to Week 64
Mean change from Baseline in domain (Symptoms, Itch, Fatigue, Cognitive, Emotional, Social) and total scores on the PBC-40
Time Frame: Baseline; up to Week 64
The PBC-40 is measures quality of life. Participants are asked to respond to 40 questions, each of which is scored on a scale of 0 to 5 (where 0=not applicable; 1=least impact; 5=greatest impact), grouped into six domains (symptoms, itch, fatigue, cognition, social, and emotional). For each domain, scoring involves summing individual question response scores. A higher score indicates a poorer quality of life.
Baseline; up to Week 64
Mean change from Baseline in each score (fibrosis, bile duct loss, deposition of orcein-positive granules) and total scores, in the stage based on the total scores, in each score of cholangitis activity and hepatitis activity on Nakanuma classification
Time Frame: Screening; Weeks 52 to 60
Scores for fibrosis, bile duct loss, and chronic cholestasis are combined for staging: stage 1, total score of 0; stage 2, score 1 to 3; stage 3, score 4 to 6; and stage 4, score 7 to 9. Cholangitis activity and hepatitis activity are graded as CA0-3 and HA0-3, respectively. A higher score indicates more severe disease.
Screening; Weeks 52 to 60
Mean values of fibrosis marker at each visit
Time Frame: Baseline; up to Week 64
The presence of serum fibrosis markers may be correlated with PBC.
Baseline; up to Week 64
Mean change from Baseline in fibrosis marker at each visit
Time Frame: Baseline; up to Week 64
The presence of serum fibrosis markers may be correlated with PBC.
Baseline; up to Week 64
Mean rate of change from Baseline in fibrosis marker at each visit
Time Frame: Baseline; up to Week 64
The presence of serum fibrosis markers may be correlated with PBC.
Baseline; up to Week 64
Mean values of fibrosis 4 (Fib-4) index at each visit
Time Frame: Baseline; up to Week 64
The presence of serum fibrosis markers may be correlated with PBC.
Baseline; up to Week 64
Mean change from Baseline in Fib-4 index at each visit
Time Frame: Baseline; up to Week 64
The presence of serum fibrosis markers may be correlated with PBC.
Baseline; up to Week 64
Mean rate of change from Baseline in Fib-4 index at each visit
Time Frame: Baseline; up to Week 64
The presence of serum fibrosis markers may be correlated with PBC.
Baseline; up to Week 64

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 29, 2017

Primary Completion (Actual)

August 27, 2018

Study Completion (Actual)

October 22, 2018

Study Registration Dates

First Submitted

March 24, 2017

First Submitted That Met QC Criteria

March 24, 2017

First Posted (Actual)

March 28, 2017

Study Record Updates

Last Update Posted (Actual)

January 4, 2019

Last Update Submitted That Met QC Criteria

January 3, 2019

Last Verified

July 1, 2018

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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