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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03092765
• Date of registration: 24/03/2017
• Prospective Registration: Yes
• Primary sponsor: EA Pharma Co., Ltd.
• Public title: Study of E6011 in Japanese Subjects With Primary Biliary Cholangitis Inadequately Responding to Ursodeoxycholic Acid
• Scientific title: A Clinical Phase 2 Study of E6011 in Japanese Subjects With Primary Biliary Cholangitis Inadequately Responding to Ursodeoxycholic Acid
• Date of first enrolment: May 29, 2017
• Target sample size: 29
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03092765
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Japan

Key inclusion & exclusion 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



Age minimum: 20 Years
Age maximum: 74 Years
Gender: All

Health Condition(s) or Problem(s) studied

Primary Biliary Cholangitis

Intervention(s)

Drug: Placebo

Drug: E6011

Primary Outcome(s)

Rate of change from Baseline in serum alkaline phosphatase (ALP) values at Week 12 [Time Frame: Baseline; Week 12]

Secondary Outcome(s)

Mean values of gamma-guanosine-5'-triphosphate (?GTP) at each visit [Time Frame: Baseline; up to Week 64]

Mean values of serum albumin at each visit [Time Frame: 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]

Number of participants with a decrease in ALP response rates of 15%, 20%, and 40% from Baseline [Time Frame: Baseline; 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]

Mean change from Baseline in Fib-4 index at each visit [Time Frame: 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]

Mean change from Baseline in serum total bilirubin and direct bilirubin at each visit [Time Frame: 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]

Mean rate of change from Baseline in serum total bilirubin and direct bilirubin at each visit [Time Frame: 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]

Mean change from Baseline in fibrosis marker at each visit [Time Frame: Baseline; up to Week 64]

Mean change from Baseline in serum ?GTP at each visit [Time Frame: Baseline; up to Week 64]

Mean rate of change from Baseline in fibrosis marker at each visit [Time Frame: Baseline; up to Week 64]

Mean values of fibrosis 4 (Fib-4) index at each visit [Time Frame: Baseline; up to Week 64]

Mean rate of change from Baseline in serum ?GTP at each visit [Time Frame: Baseline; up to Week 64]

Mean rate of change from Baseline in serum albumin at each visit [Time Frame: 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]

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]

Mean values of fibrosis marker at each visit [Time Frame: Baseline; up to Week 64]

Mean values of serum total bile acids at each visit [Time Frame: 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]

Mean change from Baseline in serum albumin at each visit [Time Frame: Baseline; up to Week 64]

Mean change from Baseline in serum total bile acids at each visit [Time Frame: 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]

Mean values of serum total bilirubin and direct bilirubin at each visit [Time Frame: Baseline; up to Week 64]

Secondary ID(s)

E6011/ET1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors