Back to resultsAn Open Label, Single Arm, Dose Escalation Phase 1 Trial of PRI-724 in Patients With HCV-induced Cirrhosis
Primary Purpose
Hepatitis C Virus-infected Cirrhosis
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
PRI-724
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C Virus-infected Cirrhosis focused on measuring Hepatitis C virus, cirrhosis
Eligibility Criteria
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 /µL.
- 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.
Sites / Locations
- Tokyo metropolitan Komagome Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PRI-724
Arm Description
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.
Outcomes
Primary Outcome Measures
Adverse events and adverse drug reactions (including subjective symptoms and abnormal laboratory values)
Items and ratio%
Secondary Outcome Measures
Child-Pugh Score
Changes of score
Liver biopsy: Histology Activity Index (HAI)
Changes of index
Serum albumin level
Changes of level
Serum fibrosis marker level(s)
Changes of level
Ascitic fluid level
Changes of level
Improvement rate of lower leg edema
Changes of rate
Assessment of Area under the plasma concentration versus time curve (AUCinf) of PRI-724 through analysis of blood samples
Comparison of AUC
Assessment of Steady State Plasma Concentration (Css) of PRI-724 through analysis of blood samples
Comparison of Css
Full Information
NCT ID
NCT02195440
First Posted
July 8, 2014
Last Updated
July 4, 2022
Sponsor
Komagome Hospital
Collaborators
Prism Pharma Co., Ltd., Japan Agency for Medical Research and Development
1. Study Identification
Unique Protocol Identification Number
NCT02195440
Brief Title
An Open Label, Single Arm, Dose Escalation Phase 1 Trial of PRI-724 in Patients With HCV-induced Cirrhosis
Official Title
An Open Label, Single Arm, Dose Escalation Phase 1 Trial of PRI-724 in Patients With HCV-induced Cirrhosis
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
March 31, 2017 (Actual)
Study Completion Date
March 31, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Komagome Hospital
Collaborators
Prism Pharma Co., Ltd., Japan Agency for Medical Research and Development
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Virus-infected Cirrhosis
Keywords
Hepatitis C virus, cirrhosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PRI-724
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
PRI-724
Other Intervention Name(s)
CBP-beta-catennin inhibitor, OP-724
Intervention Description
10 - 160 mg/m2, 7 days CIV (in the vein) with 7 days rest per one cycle. Number of Cycles: 6.
Primary Outcome Measure Information:
Title
Adverse events and adverse drug reactions (including subjective symptoms and abnormal laboratory values)
Description
Items and ratio%
Time Frame
12 weeks after the initiation of PRI-724 administration
Secondary Outcome Measure Information:
Title
Child-Pugh Score
Description
Changes of score
Time Frame
12 weeks after the initiation of PRI-724 administration
Title
Liver biopsy: Histology Activity Index (HAI)
Description
Changes of index
Time Frame
12 weeks after the initiation of PRI-724 administration
Title
Serum albumin level
Description
Changes of level
Time Frame
12 weeks after the initiation of PRI-724 administration
Title
Serum fibrosis marker level(s)
Description
Changes of level
Time Frame
12 weeks after the initiation of PRI-724 administration
Title
Ascitic fluid level
Description
Changes of level
Time Frame
12 weeks after the initiation of PRI-724 administration
Title
Improvement rate of lower leg edema
Description
Changes of rate
Time Frame
12 weeks after the initiation of PRI-724 administration
Title
Assessment of Area under the plasma concentration versus time curve (AUCinf) of PRI-724 through analysis of blood samples
Description
Comparison of AUC
Time Frame
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
Title
Assessment of Steady State Plasma Concentration (Css) of PRI-724 through analysis of blood samples
Description
Comparison of Css
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 /µL.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kiminori Kimura, MD
Organizational Affiliation
Komagome Metropolitan Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tokyo metropolitan Komagome Hospital
City
Tokyo
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
28844410
Citation
Kimura K, Ikoma A, Shibakawa M, Shimoda S, Harada K, Saio M, Imamura J, Osawa Y, Kimura M, Nishikawa K, Okusaka T, Morita S, Inoue K, Kanto T, Todaka K, Nakanishi Y, Kohara M, Mizokami M. Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/beta-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial. EBioMedicine. 2017 Sep;23:79-87. doi: 10.1016/j.ebiom.2017.08.016. Epub 2017 Aug 19.
Results Reference
derived
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An Open Label, Single Arm, Dose Escalation Phase 1 Trial of PRI-724 in Patients With HCV-induced Cirrhosis
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