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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03620474
Recruitment Status : Active, not recruiting
First Posted : August 8, 2018
Last Update Posted : April 6, 2021
Sponsor:
Collaborators:
PRISM BioLab Co.,Ltd.
Kyushu University
National Center for Global Health and Medicine, Japan
Japan Agency for Medical Research and Development
Ohara Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Kiminori Kimura, MD, Komagome Hospital

Tracking Information
First Submitted Date  ICMJE July 13, 2018
First Posted Date  ICMJE August 8, 2018
Last Update Posted Date April 6, 2021
Actual Study Start Date  ICMJE July 24, 2018
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2018)
  • Serious side effect expression rate [ Time Frame: 12 weeks after administration ]
    (Phase I)Serious side effect expression rate
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2018)
  • Adverse Event Expression Ratio [ Time Frame: 12 weeks after administration ]
    Adverse Event Expression Ratio after PRI-724 treatment
  • Percentage of occurrence of side effects [ Time Frame: 12 weeks after administration ]
    Percentage of occurrence of side effects after PRI-724 treatment
  • Pharmacokinetic parameter [ Time Frame: 12 weeks after administration ]
    Maximum Plasma Concentration (Cmax)
  • 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
  • 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).
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 3, 2018)
  • Serum fibrosis marker level(s) [ Time Frame: 12 weeks after administration ]
    Changes of level
  • Ascitic fluid level [ Time Frame: 12 weeks after administration ]
    Changes of level
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Safety and Effectiveness of PRI-724 for Hepatitis C or B Virus Derived Liver Cirrhosis
Official Title  ICMJE Phase I / IIa Clinical Trial for Patients With Hepatitis C or B Virus Derived Liver Cirrhosis by CBP / β Catenin Inhibitor PRI-724
Brief Summary To investigate the safety and efficacy of PRI-724 against HCV or HBV liver cirrhosis.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatitis C
  • Hepatitis B
  • Liver Cirrhoses
Intervention  ICMJE Drug: PRI-724
twice a week for 4 hours continuous intravenous administration of PRI-724
Other Name: CBP-b-catenin inhibitor
Study Arms  ICMJE 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.

Intervention: Drug: PRI-724
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 5, 2021)
27
Original Estimated Enrollment  ICMJE
 (submitted: August 3, 2018)
34
Estimated Study Completion Date  ICMJE March 2022
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 74 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03620474
Other Study ID Numbers  ICMJE PRI-724-2101
UMIN ( Registry Identifier: UMIN000033369 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kiminori Kimura, MD, Komagome Hospital
Study Sponsor  ICMJE Kiminori Kimura, MD
Collaborators  ICMJE
  • PRISM BioLab Co.,Ltd.
  • Kyushu University
  • National Center for Global Health and Medicine, Japan
  • Japan Agency for Medical Research and Development
  • Ohara Pharmaceutical Co., Ltd.
Investigators  ICMJE
Principal Investigator: Kiminori Kimura, MD Komagome Hospital
PRS Account Komagome Hospital
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP