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

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.

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