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

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

The purpose of this study is to investigate the safety and tolerability 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:

1. 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).
2. Child-Pugh Class A or B at the time of informed consent, with no likelihood of improvement with existing medical treatment.
3. Performance Status: 0 - 2.
4. Between =>20 and <75 years of age at the time of providing written consent.
5. Having provided voluntary written consent for participation in this study.
6. Esophageal and gastric varices are well controlled

Exclusion Criteria:

1. Patients with cirrhosis due to causes other than hepatitis C virus; or patients with cirrhosis due to unknown causes.
2. Patients with a history of primary liver cancer or a complication thereof.
3. Patients with a complication of malignant tumor or a history thereof (within 5 years prior to screening).
4. Patients in whom such active viral infections as HBV, HIV or ATCL or syphilis infection cannot be ruled out.
5. Patients with serum creatinine >1.5 times over upper normal or creatinine clearance =<60 mL/min/1.73 m2.
6. Patients with hemoglobin <8 g/dL.
7. Patients with platelet count <50,000 /&micro;L.
8. Patients with T.Bil =>3.0 mg/dL.
9. Patients with a complication of poorly controlled diabetes, hypertension or heart failure.
10. Patients with a complication of mental disorder requiring treatment.
11. Patients with serious allergy to contrast media or a history thereof.
12. Patients with allergy to inactive ingredients of the study drug.
13. Patients who have received interferon, ribavirin or anti-HCV agents within 12 weeks before registration in this study.
14. 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.
15. 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.
16. 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.
17. Patients contraindicated for liver biopsy.
18. 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.
19. Male patients who do not consent to practice birth control during the clinical study.