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

Hepatitis C Virus-infected Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02195440
• Other study ID #: PRI-724-1101
• Secondary ID: UMIN000014395
• Status: Completed
• Phase: Phase 1
• Start date: August 2014
• Est. completion date: March 31, 2017

Study information

• Verified date: July 2022
• Source: Komagome Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the safety and tolerability of PRI-724 in patients with HCV-induced cirrhosis.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: March 31, 2017
• Est. primary completion date: March 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 74 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Hepatitis
• Hepatitis C
• Hepatitis C Virus-infected Cirrhosis
• Liver Cirrhosis

Intervention

Drug:
• PRI-724
10 - 160 mg/m2, 7 days CIV (in the vein) with 7 days rest per one cycle. Number of Cycles: 6.

Locations

Country	Name	City	State
Japan	Tokyo metropolitan Komagome Hospital	Tokyo

Sponsors (3)

Lead Sponsor	Collaborator
Komagome Hospital	Japan Agency for Medical Research and Development, Prism Pharma Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events and adverse drug reactions (including subjective symptoms and abnormal laboratory values)	Items and ratio%	12 weeks after the initiation of PRI-724 administration
Secondary	Child-Pugh Score	Changes of score	12 weeks after the initiation of PRI-724 administration
Secondary	Liver biopsy: Histology Activity Index (HAI)	Changes of index	12 weeks after the initiation of PRI-724 administration
Secondary	Serum albumin level	Changes of level	12 weeks after the initiation of PRI-724 administration
Secondary	Serum fibrosis marker level(s)	Changes of level	12 weeks after the initiation of PRI-724 administration
Secondary	Ascitic fluid level	Changes of level	12 weeks after the initiation of PRI-724 administration
Secondary	Improvement rate of lower leg edema	Changes of rate	12 weeks after the initiation of PRI-724 administration
Secondary	Assessment of Area under the plasma concentration versus time curve (AUCinf) of PRI-724 through analysis of blood samples	Comparison of AUC	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
Secondary	Assessment of Steady State Plasma Concentration (Css) of PRI-724 through analysis of blood samples	Comparison of Css	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