An Open Label, Single Arm, Dose Escalation Phase 1 Trial of PRI-724 in Patients With HCV-induced Cirrhosis

This is a single-center, open-label, continuous i.v. administration, dose escalation Phase I study in patients with hepatitis C cirrhosis.

One cycle consisted of one-week continuous i.v. administration of PRI-724 followed by a one-week observation period. One cohort was a total of six cycles, a 12-week treatment period.

PRI-724 was administered at a dose of 10 mg/m2/day in Cohort 1, 40 mg/m2/day in Cohort 2, and 160 mg/m2/day in Cohort 3 in a dose escalation manner. Each cohort was to include 6 subjects.

Inclusion criteria

• Presence of cirrhosis due to hepatitis C virus. 1) Serum HCV-RNA test positive 2) Definitive diagnosis of cirrhosis established by liver biopsy (HAI score: Grade IV-D).
• Child-Pugh Class A or B at the time of informed consent, with no likelihood of improvement with existing medical treatment.
• Performance Status: 0 - 2.
• Between =>20 and <75 years of age at the time of providing written consent.
• Having provided voluntary written consent for participation in this study.
• Esophageal and gastric varices are well controlled

Exclusion criteria

• Patients with cirrhosis due to causes other than hepatitis C virus; or patients with cirrhosis due to unknown causes.
• Patients with a history of primary liver cancer or a complication thereof.
• Patients with a complication of malignant tumor or a history thereof (within 5 years prior to screening).
• Patients in whom such active viral infections as HBV, HIV or ATCL or syphilis infection cannot be ruled out.
• Patients with serum creatinine >1.5 times over upper normal or creatinine clearance =<60 mL/min/1.73 m2.
• Patients with hemoglobin <8 g/dL.
• Patients with platelet count <50,000 /&micro;L.
• Patients with T.Bil =>3.0 mg/dL.
• Patients with a complication of poorly controlled diabetes, hypertension or heart failure.
• Patients with a complication of mental disorder requiring treatment.
• Patients with serious allergy to contrast media or a history thereof.
• Patients with allergy to inactive ingredients of the study drug.
• Patients who have received interferon, ribavirin or anti-HCV agents within 12 weeks before registration in this study.
• When the medical treatment to a primary disease is carried out, Patient who was changed the dosage and administration within the 12 weeks before registration.
• Patients with a history of drug or alcohol addiction within five years at the time of providing written consent or a history of drug or alcohol abuse within the past one year.
• The patient who received a liver transplant or other organ transplants (a bone marrow transplantation is included), and the patient for whom intravenous administration and venous access are difficult.
• Patients contraindicated for liver biopsy.
• Female patients who are pregnant or suspected to be pregnant; or those who desire to get pregnant during the study period or those of childbearing potential.
• Male patients who do not consent to practice birth control during the clinical study.