Clinical trial NCT03092765: Study of E6011 in Japanese Subjects With Primary Biliary Cholangitis Inadequately Responding to Ursodeoxycholic Acid
Official title: A Clinical Phase 2 Study of E6011 in Japanese Subjects With Primary Biliary Cholangitis Inadequately Responding to Ursodeoxycholic Acid
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Primary Biliary Cholangitis
Keywords: E6011
Ursodeoxycholic acid
Japan
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2017-03-28
Enrollment: 29
Sex: ALL
Minimum age (years): 20
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Rate of change from Baseline in serum alkaline phosphatase (ALP) values at Week 12
timeFrame: Baseline; Week 12
Secondary outcomes:
measure: Number of participants with a decrease in ALP response rates of 15%, 20%, and 40% from Baseline
timeFrame: Baseline; up to Week 64
measure: 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
timeFrame: Baseline; up to Week 64
measure: Mean values of serum ALP, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) at each visit
timeFrame: Baseline; up to Week 64
measure: Mean values of gamma-guanosine-5'-triphosphate (γGTP) at each visit
timeFrame: Baseline; up to Week 64
measure: Mean values of serum total bilirubin and direct bilirubin at each visit
timeFrame: Baseline; up to Week 64
measure: Mean values of serum total bile acids at each visit
timeFrame: Baseline; up to Week 64
measure: Mean values of serum albumin at each visit
timeFrame: Baseline; up to Week 64
measure: Mean change from Baseline in serum ALP, AST, and ALT at each visit
timeFrame: Baseline; up to Week 64
measure: Mean change from Baseline in serum γGTP at each visit
timeFrame: Baseline; up to Week 64
measure: Mean change from Baseline in serum total bilirubin and direct bilirubin at each visit
timeFrame: Baseline; up to Week 64
measure: Mean change from Baseline in serum total bile acids at each visit
timeFrame: Baseline; up to Week 64
measure: Mean change from Baseline in serum albumin at each visit
timeFrame: Baseline; up to Week 64
measure: Mean rate of change from Baseline in serum ALP, AST, and ALT at each visit
timeFrame: Baseline; up to Week 64
measure: Mean rate of change from Baseline in serum γGTP at each visit
timeFrame: Baseline; up to Week 64
measure: Mean rate of change from Baseline in serum total bilirubin and direct bilirubin at each visit
timeFrame: Baseline; up to Week 64
measure: Mean rate of change from Baseline in serum total bile acids at each visit
timeFrame: Baseline; up to Week 64
measure: Mean rate of change from Baseline in serum albumin at each visit
timeFrame: Baseline; up to Week 64
measure: Mean change from Baseline in individual domain and total primary biliary cholangitis (PBC) version Child-Pugh scores
timeFrame: Screening; up to Week 64
measure: Mean change from Baseline in domain (Symptoms, Itch, Fatigue, Cognitive, Emotional, Social) and total scores on the PBC-40
timeFrame: Baseline; up to Week 64
measure: 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
timeFrame: Screening; Weeks 52 to 60
measure: Mean values of fibrosis marker at each visit
timeFrame: Baseline; up to Week 64
measure: Mean change from Baseline in fibrosis marker at each visit
timeFrame: Baseline; up to Week 64
measure: Mean rate of change from Baseline in fibrosis marker at each visit
timeFrame: Baseline; up to Week 64
measure: Mean values of fibrosis 4 (Fib-4) index at each visit
timeFrame: Baseline; up to Week 64
measure: Mean change from Baseline in Fib-4 index at each visit
timeFrame: Baseline; up to Week 64
measure: Mean rate of change from Baseline in Fib-4 index at each visit
timeFrame: Baseline; up to Week 64
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: EA Pharma trial site
state: Aichi
city: Matsudo
country: Japan
facility: EA Pharma trial site
state: Chiba
city: Touon
country: Japan
facility: EA Pharma trial site
state: Ehime
city: Yoshida
country: Japan
facility: EA Pharma trial site
state: Fukui
city: Kurume
country: Japan
facility: EA Pharma trial site
state: Fukuoka
city: Maebashi
country: Japan
facility: EA Pharma trial site
state: Gunma
city: Sapporo
country: Japan
facility: EA Pharma trial site #1
state: Hokkaido
city: Sapporo
country: Japan
facility: EA Pharma trial site #2
state: Hokkaido
city: Kobe
country: Japan
facility: EA Pharma trial site
state: Hyogo
city: Nishinomiya
country: Japan
facility: EA Pharma trial site
state: Hyogo
city: Inashiki
country: Japan
facility: EA Pharma trial site
state: Ibaraki
city: Morioka
country: Japan
facility: EA Pharma trial site
state: Iwate
city: Kita
country: Japan
facility: EA Pharma trial site
state: Kagawa
city: Takamatsu
country: Japan
facility: EA Pharma trial site
state: Kagawa
city: Yokohama
country: Japan
facility: EA Pharma trial site #1
state: Kanagawa
city: Yokohama
country: Japan
facility: EA Pharma trial site #2
state: Kanagawa
city: Sendai
country: Japan
facility: EA Pharma trial site
state: Miyagi
city: Matsumoto
country: Japan
facility: EA Pharma trial site
state: Nagano
city: Oomura
country: Japan
facility: EA Pharma trial site
state: Nagasaki
city: Kashihara
country: Japan
facility: EA Pharma trial site
state: Nara
city: Nakagami
country: Japan
facility: EA Pharma trial site
state: Okinawa
city: Hirakata
country: Japan
facility: EA Pharma trial site
state: Osaka
city: Suita
country: Japan
facility: EA Pharma trial site #1
state: Osaka
city: Suita
country: Japan
facility: EA Pharma trial site #2
state: Osaka
city: Ageo
country: Japan
facility: EA Pharma trial site
state: Saitama
city: Iruma
country: Japan
facility: EA Pharma trial site
state: Saitama
city: Shimotsuga
country: Japan
facility: EA Pharma trial site
state: Tochigi
city: Bunkyo
country: Japan
facility: EA Pharma trial site
state: Tokyo
city: Itabashi
country: Japan
facility: EA Pharma trial site
state: Tokyo
city: Minato
country: Japan
facility: EA Pharma trial site #1
state: Tokyo
city: Minato
country: Japan
facility: EA Pharma trial site #2
state: Tokyo
city: Musashino
country: Japan
facility: EA Pharma trial site
state: Tokyo
city: Shinjuku
country: Japan
facility: EA Pharma trial site
state: Tokyo
city: Fukuoka
country: Japan
facility: EA Pharma trial site #1
city: Fukuoka
country: Japan
facility: EA Pharma trial site #2
city: Fukushima
country: Japan
facility: EA Pharma trial site
city: Hiroshima
country: Japan
facility: EA Pharma trial site #1
city: Hiroshima
country: Japan
facility: EA Pharma trial site #2
city: Kagoshima
country: Japan
facility: EA Pharma trial site
city: Kumamoto
country: Japan
facility: EA Pharma trial site
city: Kyoto
country: Japan
facility: EA Pharma trial site
city: Niigata
country: Japan
facility: EA Pharma trial site
city: Okayama
country: Japan
facility: EA Pharma trial site
city: Osaka
country: Japan
facility: EA Pharma trial site
city: Saga
country: Japan
facility: EA Pharma trial site
city: Yamagata
country: Japan
facility: EA Pharma trial site
Study officials:
References: