Safety and Effectiveness of PRI-724 for Hepatitis C or B Virus Derived Liver Cirrhosis

July 4, 2022 updated by: Kiminori Kimura, MD

Phase I / IIa Clinical Trial for Patients With Hepatitis C or B Virus Derived Liver Cirrhosis by CBP / β Catenin Inhibitor PRI-724

To investigate the safety and efficacy of PRI-724 against HCV or HBV liver cirrhosis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

【Phase I Phase】 To evaluate safety and pharmacokinetics when PRI-724 is administered to patients with HCV or HBV liver cirrhosis , and determine the recommended dose of PRI-724.

【Phase IIa phase】 To evaluate the efficacy and safety of the recommended dose of PRI-724 administered to patients with HCV or HBV liver cirrhosis.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Fukuoka, Japan, 812-8582
        • Kyushu University Hospital
    • Chiba
      • Ichikawa, Chiba, Japan, 272-8516
        • Kohnodai Hospital, National Center for Global Health and Medicine
    • Tokyo
      • Bunkyō-Ku, Tokyo, Japan, 113-8677
        • Tokyo Metropolitan Komagome Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with liver cirrhosis caused by HCV or HBV that satisfies the following (1) or (2) and satisfies (3)

    1. Patients with serum HCV-RNA positive or HCV antibody positive
    2. Patients with serum HBV-DNA positive or HBs antigen positive
    3. confirmed liver cirrhosis by liver biopsy performed in the screening period patients who received diagnosis
  • Patients with Child-Pugh classification in A or B status

  • Patients who satisfy HCV cirrhosis from (1) to (3), HBV cirrhosis (4) In the case of HCV cirrhosis;

    1. Patients who have not reached SVR * with DAA therapy
    2. Patients who are difficult to implement DAA therapy
    3. Patients who have been over 24 weeks after achieving SVR * with DAA therapy In case of HBV cirrhosis;
    4. Patients who have been at least 24 weeks since the start of administration of Nucleotide analogue * SVR is SVR 12 (sustained virological response at 12 weeks after the end of administration).
  • Patients with Performance Status 0 to 2
  • Patients aged 20 years or over and under 75 when acquiring informed consent
  • Regarding participation in this trial (including liver biopsy), patients who obtained informed consent by their own voluntary intention

Exclusion Criteria:

  • Patients with HCV and HBV co-infection, patients who came to cirrhosis due to causes other than HCV or HBV, or patients whose cause of cirrhosis is unknown
  • Patients with esophageal gastric varices determined to be treated by endoscopic examination at screening
  • Patients with complication or previous history of primary liver cancer (excluding those who have had more than one year of hepatocarcinoma resection / radiofrequency ablation)
  • Merger of malignant tumor or past patients (within 3 years before screening). However, the following diseases are excluded: treated basal cell carcinoma, treated lung intraepithelial carcinoma, treated cervical carcinoma, or control superficial (not invasive) bladder carcinoma
  • Patients who can not be denied HIV, HTLV-1 or syphilis
  • Serum creatinine value: Patients with more than 1.5 times the upper limit of the facility reference value
  • Patients with poor control of diabetes, hypertension or heart failure
  • Patients with psychiatric diseases judged to have the potential to influence the implementation of clinical trials
  • Patients who have severe allergy to or contrast media

  • Patients with HCV who have not passed the following period after treatment for HCV cirrhosis at registration.

    • 12 weeks after the final administration of interferon
    • 16 weeks after final administration of Ribavirin
    • 16 weeks after final administration of DAA
  • Patients whose dosage regimen was changed within 12 weeks prior to enrollment
  • Patients who have history of drug or alcohol intoxication within 5 years before acquiring informed consent or who have history of drug or alcohol abuse within the past year
  • Patients who participated in other clinical trials and clinical trials within 30 days prior to acquisition of consent, patients who used investigational drugs or investigational equipment
  • Patients who received liver transplantation or other organ transplantation (including bone marrow transplantation) and patients who are difficult to intravenously administer
  • Patients whose liver biopsy is expected to be difficult to perform
  • Patients who are pregnant or nursing, or who are likely to become pregnant
  • Male patients who do not obtain consent to contraception from the time of acquiring informed consent until the end of 12 weeks after the administration of investigational drug
  • In addition, patients investigated by investigators or clinical trial doctors as judged unsuitable for this trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PRI-724

Dose: 140, 280, 380 mg / m 2/4 hr

Administration method:

【Phase I Phase】 (Level 1) 140 mg / m 2/4 hr (Level 2) 280 mg / m 2/4 hr (Level 3) 380 mg / m 2/4 hr Twice weekly, continuous 4-hour intravenous administration (tolerance of administration time: ± 15 minutes). This is one cycle and 12 cycles (12 weeks in total) are carried out. However, in Phase I phase, single dose is administered on Day - 7 (tolerance: - 7 days).

【Phase IIa phase】 Continuous intravenous administration for 4 hours twice a week at the recommended dose determined in Phase I. This is one cycle and 12 cycles (12 weeks in total) are carried out.
Drug: PRI-724
twice a week for 4 hours continuous intravenous administration of PRI-724
Other Names:
  • CBP-b-catenin inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serious side effect expression rate
Time Frame: 12 weeks after administration
(Phase I)Serious side effect expression rate
12 weeks after administration
liver tissue fibrosis area ratio by liver biopsy
Time Frame: 12 weeks after administration
(Phase II) Amount of change from the baseline in liver tissue fibrosis area ratio by liver biopsy at 12 weeks after administration
12 weeks after administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Event Expression Ratio
Time Frame: 12 weeks after administration
Adverse Event Expression Ratio after PRI-724 treatment
12 weeks after administration
Percentage of occurrence of side effects
Time Frame: 12 weeks after administration
Percentage of occurrence of side effects after PRI-724 treatment
12 weeks after administration
Pharmacokinetic parameter
Time Frame: 12 weeks after administration
Maximum Plasma Concentration (Cmax)
12 weeks after administration
liver stiffness from Fibro Scan
Time Frame: 12 weeks after administration
Amount of change from measurement of liver stiffness by baseline from Fibro Scan at 12 weeks after administration
12 weeks after administration
Child Pugh score
Time Frame: 12 weeks after administration
Amount of change from baseline of Child-Pugh Score at 12 weeks after administration Child Pugh score (scale range 5-15) is obtained by adding the score for each parameter (encephalopathy, ascites, bilirubin, albumin, PT or INR).
12 weeks after administration
MELD score
Time Frame: 12 weeks after administration

Amount of change from baseline for MELD score at 12 weeks after administration

The Model for End-Stage Liver Disease (MELD) is a scoring system for assessing the severity of chronic liver disease and uses the subject's values for total bilirubin, serum creatinine, and the international normalized ratio (INR) for prothrombin time to predict survival. MELD is calculated according to the following formula:

MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43
12 weeks after administration
modified Histological Activity Index (HAI) by liver biopsy
Time Frame: 12 weeks after administration
Change amount from baseline of modified Histological Activity Index (HAI) by liver biopsy at 12 weeks after administration
12 weeks after administration

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum fibrosis marker level(s)
Time Frame: 12 weeks after administration
Changes of level
12 weeks after administration
Ascitic fluid level
Time Frame: 12 weeks after administration
Changes of level
12 weeks after administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kiminori Kimura, MD

Collaborators

Japan Agency for Medical Research and Development
Prism Pharma Co., Ltd.
National Center for Global Health and Medicine, Japan
Kyushu University
Ohara Pharmaceutical Co., Ltd.

Investigators

  • Principal Investigator: Kiminori Kimura, MD, Komagome Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 24, 2018

Primary Completion (Actual)

July 13, 2021

Study Completion (Actual)

February 28, 2022

Study Registration Dates

First Submitted

July 13, 2018

First Submitted That Met QC Criteria

August 3, 2018

First Posted (Actual)

August 8, 2018

Study Record Updates

Last Update Posted (Actual)

July 7, 2022

Last Update Submitted That Met QC Criteria

July 4, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRI-724-2101
  • UMIN000033369 (Registry Identifier: UMIN (University Hospital Medical Information) CTR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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