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

NCT03620474 | Completed Phase 1 DMC

• 2 other identifiers: PRI-724-2101UMIN000033369
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Hepatitis C; Hepatitis B; Liver Cirrhoses

Keywords

Hepatitis C virus; Hepatitis B virus; liver Cirrhosis

Outcome Measures

Primary Outcomes (2)

• Serious side effect expression rate

  (Phase I)Serious side effect expression rate

  12 weeks after administration

• 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 Outcomes (7)

• Adverse Event Expression Ratio

  12 weeks after administration

• Percentage of occurrence of side effects

  12 weeks after administration

• Pharmacokinetic parameter

  12 weeks after administration

• liver stiffness from Fibro Scan

  12 weeks after administration

• Child Pugh score

  12 weeks after administration

Other Outcomes (2)

• Serum fibrosis marker level(s)

  12 weeks after administration

• Ascitic fluid level

  12 weeks after administration

Study Arms (1)

PRI-724

EXPERIMENTAL

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

Interventions

PRI-724 DRUG

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

Also known as: CBP-b-catenin inhibitor

PRI-724

Eligibility Criteria

• Age: 20 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with liver cirrhosis caused by HCV or HBV that satisfies the following (1) or (2) and satisfies (3)
• Patients with serum HCV-RNA positive or HCV antibody positive
• Patients with serum HBV-DNA positive or HBs antigen positive
• 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;
• Patients who have not reached SVR \* with DAA therapy
• Patients who are difficult to implement DAA therapy
• Patients who have been over 24 weeks after achieving SVR \* with DAA therapy In case of HBV cirrhosis;
• 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

You may not qualify if:

• 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.
• weeks after the final administration of interferon
• weeks after final administration of Ribavirin
• 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

Sponsors & Collaborators

• Kiminori Kimura, MD: lead
• Prism Pharma Co., Ltd.: collaborator
• Kyushu University: collaborator
• National Center for Global Health and Medicine, Japan: collaborator
• Japan Agency for Medical Research and Development: collaborator
• Ohara Pharmaceutical Co., Ltd.: collaborator

Study Sites (3)

Kohnodai Hospital, National Center for Global Health and Medicine

Ichikawa, Chiba, 272-8516, Japan

Location

Tokyo Metropolitan Komagome Hospital

Bunkyō-Ku, Tokyo, 113-8677, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Related Publications (1)

• 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.

  PMID: 35605429 DERIVED

MeSH Terms

Conditions

Hepatitis C; Hepatitis B; Liver Cirrhosis

Interventions

ICG 001

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Hepadnaviridae Infections; DNA Virus Infections; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kiminori Kimura, MD

  Komagome Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head, Department of Hepatology

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: August 8, 2018
• Study Start: July 24, 2018
• Primary Completion: July 13, 2021
• Study Completion: February 28, 2022
• Last Updated: October 10, 2024

Record last verified: 2024-10

Locations

JP (3)