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

NCT03092765 | Terminated Phase 2 DMC

• 1 other identifier: E6011/ET1
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 46

Brief Summary

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

Conditions

Primary Biliary Cholangitis

Keywords

E6011; Ursodeoxycholic acid; Japan

Outcome Measures

Primary Outcomes (1)

• Rate of change from Baseline in serum alkaline phosphatase (ALP) values at Week 12

  This assessment will be conducted as a measure of efficacy.

  Baseline; Week 12

Secondary Outcomes (26)

• Number of participants with a decrease in ALP response rates of 15%, 20%, and 40% from Baseline

  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

  Baseline; up to Week 64

• Mean values of serum ALP, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) at each visit

  Baseline; up to Week 64

• Mean values of gamma-guanosine-5'-triphosphate (γGTP) at each visit

  Baseline; up to Week 64

• Mean values of serum total bilirubin and direct bilirubin at each visit

  Baseline; up to Week 64

Study Arms (8)

low-dose, high-frequency E6011; high-dose, low-frequency E6011

EXPERIMENTAL

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.

Drug: E6011

low-dose, high-frequency E6011; low-dose, low-frequency E6011

EXPERIMENTAL

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.

Drug: E6011

high-dose, low-frequency E6011; high-dose, low-frequency E6011

EXPERIMENTAL

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.

Drug: E6011

high-dose, low-frequency E6011; low-dose, low-frequency E6011

EXPERIMENTAL

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.

Drug: E6011

low-dose, low-frequency E6011; high-dose, low-frequency E6011

EXPERIMENTAL

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.

Drug: E6011

low-dose, low-frequency E6011; low-dose, low-frequency E6011

EXPERIMENTAL

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.

Drug: E6011

Placebo; high-dose, low-frequency E6011

EXPERIMENTAL

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.

Drug: E6011; Drug: Placebo

Placebo; low-dose, low-frequency E6011

EXPERIMENTAL

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.

Drug: E6011; Drug: Placebo

Interventions

E6011 DRUG

Intravenous administration

Placebo; high-dose, low-frequency E6011; Placebo; low-dose, low-frequency E6011; high-dose, low-frequency E6011; high-dose, low-frequency E6011; high-dose, low-frequency E6011; low-dose, low-frequency E6011; low-dose, high-frequency E6011; high-dose, low-frequency E6011; low-dose, high-frequency E6011; low-dose, low-frequency E6011; low-dose, low-frequency E6011; high-dose, low-frequency E6011; low-dose, low-frequency E6011; low-dose, low-frequency E6011

Placebo DRUG

Intravenous administration

Placebo; high-dose, low-frequency E6011; Placebo; low-dose, low-frequency E6011

Eligibility Criteria

• Age: 20 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EA Pharma Co., Ltd.: lead

Study Sites (46)

EA Pharma trial site

Nagoya, Aichi-ken, Japan

Location

EA Pharma trial site

Matsudo, Chiba, Japan

Location

EA Pharma trial site

Touon, Ehime, Japan

Location

EA Pharma trial site

Yoshida, Fukui, Japan

Location

EA Pharma trial site

Kurume, Fukuoka, Japan

Location

EA Pharma trial site

Maebashi, Gunma, Japan

Location

EA Pharma trial site #1

Sapporo, Hokkaido, Japan

Location

EA Pharma trial site #2

Sapporo, Hokkaido, Japan

Location

EA Pharma trial site

Kobe, Hyōgo, Japan

Location

EA Pharma trial site

Nishinomiya, Hyōgo, Japan

Location

EA Pharma trial site

Inashiki, Ibaraki, Japan

Location

EA Pharma trial site

Morioka, Iwate, Japan

Location

EA Pharma trial site

Kita, Kagawa-ken, Japan

Location

EA Pharma trial site

Takamatsu, Kagawa-ken, Japan

Location

EA Pharma trial site #1

Yokohama, Kanagawa, Japan

Location

EA Pharma trial site #2

Yokohama, Kanagawa, Japan

Location

EA Pharma trial site

Sendai, Miyagi, Japan

Location

EA Pharma trial site

Matsumoto, Nagano, Japan

Location

EA Pharma trial site

Oomura, Nagasaki, Japan

Location

EA Pharma trial site

Kashihara, Nara, Japan

Location

EA Pharma trial site

Nakagami, Okinawa, Japan

Location

EA Pharma trial site

Hirakata, Osaka, Japan

Location

EA Pharma trial site #1

Suita, Osaka, Japan

Location

EA Pharma trial site #2

Suita, Osaka, Japan

Location

EA Pharma trial site

Ageo, Saitama, Japan

Location

EA Pharma trial site

Iruma, Saitama, Japan

Location

EA Pharma trial site

Shimotsuga, Tochigi, Japan

Location

EA Pharma trial site

Bunkyo, Tokyo, Japan

Location

EA Pharma trial site #1

Minato, Tokyo, Japan

Location

EA Pharma trial site #2

Minato, Tokyo, Japan

Location

EA Pharma trial site

Musashino, Tokyo, Japan

Location

EA Pharma trial site

Shinjuku, Tokyo, Japan

Location

EA Pharma trial site

tabashi City, Tokyo, Japan

Location

EA Pharma trial site #1

Fukuoka, Japan

Location

EA Pharma trial site #2

Fukuoka, Japan

Location

EA Pharma trial site

Fukushima, Japan

Location

EA Pharma trial site #1

Hiroshima, Japan

Location

EA Pharma trial site #2

Hiroshima, Japan

Location

EA Pharma trial site

Kagoshima, Japan

Location

EA Pharma trial site

Kumamoto, Japan

Location

EA Pharma trial site

Kyoto, Japan

Location

EA Pharma trial site

Niigata, Japan

Location

EA Pharma trial site

Okayama, Japan

Location

EA Pharma trial site

Osaka, Japan

Location

EA Pharma trial site

Saga, Japan

Location

EA Pharma trial site

Yamagata, Japan

Location

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

quetmolimab

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2017
• First Posted: March 28, 2017
• Study Start: May 29, 2017
• Primary Completion: August 27, 2018
• Study Completion: October 22, 2018
• Last Updated: January 4, 2019

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (46)