A Clinical Phase 2 Study of E6011 in Japanese Subjects with Primary Biliary Cholangitis Inadequately Responding to Ursodeoxycholic Acid
- Conditions
- Primary Biliary Cholangitis
- Registration Number
- JPRN-jRCT2080223460
- Lead Sponsor
- EA Pharma Co.,Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- terminated
- Sex
- All
- Target Recruitment
- 80
Main inclusion criteria
1. 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 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
2. Taking stable dose of ursodeoxycholic acid for at least 6 months (>= 600mg/day ) prior to Screening
3. Screening and Week 0 ALP values between 1.67 and 10 times upper limit normal
4. Outpatient
5. Has voluntarily consented, in writing, to participate in this study, and is able to comply with all aspects of the protocol
Main exclusion criteria
1. Received following drugs within 12 weeks before starting the study treatment
- Drugs which suppose the efficacy to PBC: azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, penicillamine, fibrates and other systemic corticosteroids
- Potentially hepatotoxic drugs: methyl-dopa, sodium valproic acid and isoniazide
2. History or current condition of hepatic decompensation with variceal bleeds, encephalopathy >= grade 2 and poorly controlled ascites, and history of liver transplantation
3. History or current condition of other concomitant liver diseases including hepatitis due to HBV/HCV infection, primary sclerosing cholangitis, alcoholic liver disease (including liver cirrhosis), autoimmune liver disease requiring the treatment of systemic corticosteroids or biopsy proven NASH.
4. 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
5. Immunodeficiency or history of human immunodeficiency virus (HIV) infection
6. Infection requiring hospitalization or intravenous administration of antibiotics or disease requiring administration of antivirus drugs (e.g., herpes zoster) within 4 weeks before starting the study treatment
7. History of tuberculosis or current complication of active tuberculosis
8. Positive in tuberculosis test ( T-SPOT TB Test or QuantiFERON.TB Gold Test) at Screening
9. History of clinically important vasculitis
10. History of severe allergy (shock or anaphylactoid symptoms)
11. Complication of uncontrolled disorders such as acute cardiac infarction, unstable angina, brain infarct, or symptomatic intracerebral hemorrhage
12. Evidence of clinically significant disease (e.g., 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
13. Tested positive for any of the following at Screening: HIV, HBs antigen, HBs antibody, HBc antibody, HBV DNA, HCV antibody, HTLV-1 antibody, or syphilis
14. Demonstrated prolonged QTcF interval (>450 ms) in repeated electrocardiogram examinations
15. Received immunoglobulin preparations or blood products within 24 weeks before starting the study treatment
16. Received a live vaccine within 12 weeks before starting the study treatment, or is planning to receive
17. 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
18. Scheduled for surgery before Week 64
19. Has been treated with investigational drugs in other E6011 study
20. Currently enrolled in another clinical study, including the follow-up
21. Used any investigational drug within 28 days (or 5x the half-life, whichever is longer) prior to Screening
22. Judged to be ineligible to participate in this study by the investigator or sub-investigator
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method efficacy<br>Rate of change in serum ALP values from baseline to Week 12
- Secondary Outcome Measures
Name Time Method safety<br>efficacy<br>Main secondary outcome<br>- Number of participants with a decrease in ALP response rates of 15%, 20%, and 40% from Baseline<br>- Number of participants with an ALP value less than 1.67 times upper limit normal and total bilirubin value within normal limits and greater than or equal to 15% decrease in ALP from Baseline<br>- 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 cholagitis activity and hepatitis activity on Nakanuma classification