Clinical trial NCT03620474: Safety and Effectiveness of PRI-724 for Hepatitis C or B Virus Derived Liver Cirrhosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hepatitis C
Hepatitis B
Liver Cirrhoses
Keywords: Hepatitis C virus
Hepatitis B virus
liver Cirrhosis
Lead sponsor: Komagome Hospital
Sponsor class: OTHER
Collaborators: name: Prism Pharma Co., Ltd.
name: Kyushu University
name: National Center for Global Health and Medicine, Japan
name: Japan Agency for Medical Research and Development
name: Ohara Pharmaceutical Co., Ltd.
First posted: 2018-08-08
Enrollment: 27
Sex: ALL
Minimum age (years): 20
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Serious side effect expression rate
timeFrame: 12 weeks after administration
measure: liver tissue fibrosis area ratio by liver biopsy
timeFrame: 12 weeks after administration
Secondary outcomes:
measure: Adverse Event Expression Ratio
timeFrame: 12 weeks after administration
measure: Percentage of occurrence of side effects
timeFrame: 12 weeks after administration
measure: Pharmacokinetic parameter
timeFrame: 12 weeks after administration
measure: liver stiffness from Fibro Scan
timeFrame: 12 weeks after administration
measure: Child Pugh score
timeFrame: 12 weeks after administration
measure: MELD score
timeFrame: 12 weeks after administration
measure: modified Histological Activity Index (HAI) by liver biopsy
timeFrame: 12 weeks after administration
Other outcomes:
measure: Serum fibrosis marker level(s)
timeFrame: 12 weeks after administration
measure: Ascitic fluid level
timeFrame: 12 weeks after administration
Locations:
city: Ichikawa
country: Japan
facility: Kohnodai Hospital, National Center for Global Health and Medicine
state: Chiba
city: Bunkyō-Ku
country: Japan
facility: Tokyo Metropolitan Komagome Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
Study officials:
affiliation: Komagome Hospital
name: Kiminori Kimura, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kimura K, Kanto T, Shimoda S, Harada K, Kimura M, Nishikawa K, Imamura J, Ogawa E, Saio M, Ikura Y, Okusaka T, Inoue K, Ishikawa T, Ieiri I, Kishimoto J, Todaka K, Kamisawa T. Safety, tolerability, and anti-fibrotic efficacy of the CBP/beta-catenin inhibitor PRI-724 in patients with hepatitis C and B virus-induced liver cirrhosis: An investigator-initiated, open-label, non-randomised, multicentre, phase 1/2a study. EBioMedicine. 2022 Jun;80:104069. doi: 10.1016/j.ebiom.2022.104069. Epub 2022 May 20.