Safety and Effectiveness of PRI-724 for Hepatitis C or B Virus Derived Liver Cirrhosis

【Phase I Phase】 To evaluate safety and pharmacokinetics when PRI-724 is administered to patients with HCV or HBV liver cirrhosis , and determine the recommended dose of PRI-724.

【Phase IIa phase】 To evaluate the efficacy and safety of the recommended dose of PRI-724 administered to patients with HCV or HBV liver cirrhosis.

Inclusion criteria

• Patients with liver cirrhosis caused by HCV or HBV that satisfies the following (1) or (2) and satisfies (3)

• Patients with serum HCV-RNA positive or HCV antibody positive
• Patients with serum HBV-DNA positive or HBs antigen positive
• confirmed liver cirrhosis by liver biopsy performed in the screening period patients who received diagnosis
• Patients with Child-Pugh classification in A or B status
• Patients who satisfy HCV cirrhosis from (1) to (3), HBV cirrhosis (4) In the case of HCV cirrhosis;

• Patients who have not reached SVR * with DAA therapy
• Patients who are difficult to implement DAA therapy
• Patients who have been over 24 weeks after achieving SVR * with DAA therapy In case of HBV cirrhosis;
• Patients who have been at least 24 weeks since the start of administration of Nucleotide analogue * SVR is SVR 12 (sustained virological response at 12 weeks after the end of administration).
• Patients with Performance Status 0 to 2
• Patients aged 20 years or over and under 75 when acquiring informed consent
• Regarding participation in this trial (including liver biopsy), patients who obtained informed consent by their own voluntary intention

Exclusion criteria

• Patients with HCV and HBV co-infection, patients who came to cirrhosis due to causes other than HCV or HBV, or patients whose cause of cirrhosis is unknown
• Patients with esophageal gastric varices determined to be treated by endoscopic examination at screening
• Patients with complication or previous history of primary liver cancer (excluding those who have had more than one year of hepatocarcinoma resection / radiofrequency ablation)
• Merger of malignant tumor or past patients (within 3 years before screening). However, the following diseases are excluded: treated basal cell carcinoma, treated lung intraepithelial carcinoma, treated cervical carcinoma, or control superficial (not invasive) bladder carcinoma
• Patients who can not be denied HIV, HTLV-1 or syphilis
• Serum creatinine value: Patients with more than 1.5 times the upper limit of the facility reference value
• Patients with poor control of diabetes, hypertension or heart failure
• Patients with psychiatric diseases judged to have the potential to influence the implementation of clinical trials
• Patients who have severe allergy to or contrast media
• Patients with HCV who have not passed the following period after treatment for HCV cirrhosis at registration.

• 12 weeks after the final administration of interferon
• 16 weeks after final administration of Ribavirin
• 16 weeks after final administration of DAA
• Patients whose dosage regimen was changed within 12 weeks prior to enrollment
• Patients who have history of drug or alcohol intoxication within 5 years before acquiring informed consent or who have history of drug or alcohol abuse within the past year
• Patients who participated in other clinical trials and clinical trials within 30 days prior to acquisition of consent, patients who used investigational drugs or investigational equipment
• Patients who received liver transplantation or other organ transplantation (including bone marrow transplantation) and patients who are difficult to intravenously administer
• Patients whose liver biopsy is expected to be difficult to perform
• Patients who are pregnant or nursing, or who are likely to become pregnant
• Male patients who do not obtain consent to contraception from the time of acquiring informed consent until the end of 12 weeks after the administration of investigational drug
• In addition, patients investigated by investigators or clinical trial doctors as judged unsuitable for this trial