Hepatitis C Virus-infected Cirrhosis
Conditions
Keywords
Hepatitis C virus, cirrhosis
Brief summary
The purpose of this study is to investigate the safety and tolerability of PRI-724 in patients with HCV-induced cirrhosis.
Detailed description
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.
Interventions
DRUGPRI-724
10 - 160 mg/m2, 7 days CIV (in the vein) with 7 days rest per one cycle. Number of Cycles: 6.
Sponsors
Prism Pharma Co., Ltd.
Japan Agency for Medical Research and Development
Komagome Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
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 /µL. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events and adverse drug reactions (including subjective symptoms and abnormal laboratory values) | 12 weeks after the initiation of PRI-724 administration | Items and ratio% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Child-Pugh Score | 12 weeks after the initiation of PRI-724 administration | Changes of score |
| Liver biopsy: Histology Activity Index (HAI) | 12 weeks after the initiation of PRI-724 administration | Changes of index |
| Serum albumin level | 12 weeks after the initiation of PRI-724 administration | Changes of level |
| Serum fibrosis marker level(s) | 12 weeks after the initiation of PRI-724 administration | Changes of level |
| Ascitic fluid level | 12 weeks after the initiation of PRI-724 administration | Changes of level |
| Improvement rate of lower leg edema | 12 weeks after the initiation of PRI-724 administration | Changes of rate |
| Assessment of Area under the plasma concentration versus time curve (AUCinf) of PRI-724 through analysis of blood samples | Days 1-2 for preinfusion, 0.5, 1.0, 2.0, 4.0, and 24h; Day 7-8 for prestopping, 0.5, 1.0, 2.0, 4.0, and 24h | Comparison of AUC |
| Assessment of Steady State Plasma Concentration (Css) of PRI-724 through analysis of blood samples | Days 1-2 for preinfusion, 0.5, 1.0, 2.0, 4.0, and 24h; Day 7-8 for prestopping, 0.5, 1.0, 2.0, 4.0, and 24h | Comparison of Css |
Countries
Japan
Outcome results
None listed