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

Phase 1

Completed

• Conditions: Hepatitis C Virus-infected Cirrhosis
• Interventions: Drug: PRI-724

• Registration Number: NCT02195440
• Lead Sponsor: Komagome Hospital

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.

Study Timeline

• Study First Submitted: 2014-07-08
• Study First Submitted QC: 2014-07-17
• Study First Posted: 2014-07-21
• Study Start: 2014-08
• Primary Completion: 2017-03-31
• Study Completion: 2017-03-31
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-04
• Last Update Posted: 2022-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PRI-724	PRI-724	3 cohorts (PRI-724: 10, 40, 160 mg/m2/day), 6 cycles (1 cycle: 1-week continuous i.v. administration+1-week observation period) \*Cycle 2 will not be started until plasma drug concentrations of PRI-724 and C-82 on Days 1 and 2 in Cycle 1 are confirmed. Cohort 1: 10 mg/m2/day (6 subjects) Cohort 2: 40 mg/m2/day (6 subjects) Cohort 3: 160 mg/m2/day (6 subjects) One cycle consists of 1-week continuous i.v. administration of PRI-724 followed by a 1-week observation period. The tolerability and safety after 6 cycles will be confirmed.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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
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
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

Trial Locations

Locations (1)

Tokyo metropolitan Komagome Hospital; 🇯🇵 Tokyo, Japan