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

Hepatitis C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03620474
• Other study ID #: PRI-724-2101
• Secondary ID: UMIN000033369
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 24, 2018
• Est. completion date: February 28, 2022

Study information

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

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: February 28, 2022
• Est. primary completion date: July 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis C
• Liver Cirrhoses
• Liver Cirrhosis

Intervention

Drug:
• PRI-724
twice a week for 4 hours continuous intravenous administration of PRI-724

Locations

Country	Name	City	State
Japan	Tokyo Metropolitan Komagome Hospital	Bunkyo-Ku	Tokyo
Japan	Kyushu University Hospital	Fukuoka
Japan	Kohnodai Hospital, National Center for Global Health and Medicine	Ichikawa	Chiba

Sponsors (6)

Lead Sponsor	Collaborator
Kiminori Kimura, MD	Japan Agency for Medical Research and Development, Kyushu University, National Center for Global Health and Medicine, Japan, Ohara Pharmaceutical Co., Ltd., Prism Pharma Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum fibrosis marker level(s)	Changes of level	12 weeks after administration
Other	Ascitic fluid level	Changes of level	12 weeks after administration
Primary	Serious side effect expression rate	(Phase I)Serious side effect expression rate	12 weeks after administration
Primary	liver tissue fibrosis area ratio by liver biopsy	(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	Adverse Event Expression Ratio	Adverse Event Expression Ratio after PRI-724 treatment	12 weeks after administration
Secondary	Percentage of occurrence of side effects	Percentage of occurrence of side effects after PRI-724 treatment	12 weeks after administration
Secondary	Pharmacokinetic parameter	Maximum Plasma Concentration (Cmax)	12 weeks after administration
Secondary	liver stiffness from Fibro Scan	Amount of change from measurement of liver stiffness by baseline from Fibro Scan at 12 weeks after administration	12 weeks after administration
Secondary	Child Pugh score	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
Secondary	MELD score	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
Secondary	modified Histological Activity Index (HAI) by liver biopsy	Change amount from baseline of modified Histological Activity Index (HAI) by liver biopsy at 12 weeks after administration	12 weeks after administration