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

Primary Biliary Cholangitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03092765
• Other study ID #: E6011/ET1
• Status: Terminated
• Phase: Phase 2
• Start date: May 29, 2017
• Est. completion date: October 22, 2018

Study information

• Verified date: July 2018
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: October 22, 2018
• Est. primary completion date: August 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Cholangitis
• Liver Cirrhosis, Biliary
• Primary Biliary Cholangitis

Intervention

Drug:
• E6011
Intravenous administration
• Placebo
Intravenous administration

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
EA Pharma Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of participants with a decrease in ALP response rates of 15%, 20%, and 40% from Baseline	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	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	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean values of serum ALP, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean values of gamma-guanosine-5'-triphosphate (?GTP) at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean values of serum total bilirubin and direct bilirubin at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean values of serum total bile acids at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean values of serum albumin at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean change from Baseline in serum ALP, AST, and ALT at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean change from Baseline in serum ?GTP at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean change from Baseline in serum total bilirubin and direct bilirubin at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean change from Baseline in serum total bile acids at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean change from Baseline in serum albumin at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean rate of change from Baseline in serum ALP, AST, and ALT at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean rate of change from Baseline in serum ?GTP at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean rate of change from Baseline in serum total bilirubin and direct bilirubin at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean rate of change from Baseline in serum total bile acids at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean rate of change from Baseline in serum albumin at each visit	This assessment will be conducted as a measure of efficacy.	Baseline; up to Week 64
Secondary	Mean change from Baseline in individual domain and total primary biliary cholangitis (PBC) version Child-Pugh scores	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
Secondary	Mean change from Baseline in domain (Symptoms, Itch, Fatigue, Cognitive, Emotional, Social) and total scores on the PBC-40	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
Secondary	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	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
Secondary	Mean values of fibrosis marker at each visit	The presence of serum fibrosis markers may be correlated with PBC.	Baseline; up to Week 64
Secondary	Mean change from Baseline in fibrosis marker at each visit	The presence of serum fibrosis markers may be correlated with PBC.	Baseline; up to Week 64
Secondary	Mean rate of change from Baseline in fibrosis marker at each visit	The presence of serum fibrosis markers may be correlated with PBC.	Baseline; up to Week 64
Secondary	Mean values of fibrosis 4 (Fib-4) index at each visit	The presence of serum fibrosis markers may be correlated with PBC.	Baseline; up to Week 64
Secondary	Mean change from Baseline in Fib-4 index at each visit	The presence of serum fibrosis markers may be correlated with PBC.	Baseline; up to Week 64
Secondary	Mean rate of change from Baseline in Fib-4 index at each visit	The presence of serum fibrosis markers may be correlated with PBC.	Baseline; up to Week 64