An Open Label, Single Arm, Dose Escalation Phase 1 Trial of PRI-724 in Patients With HCV-induced Cirrhosis

NCT02195440 | Completed Phase 1 DMC

• 2 other identifiers: PRI-724-1101UMIN000014395
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the safety and tolerability of PRI-724 in patients with HCV-induced cirrhosis.

Conditions

Hepatitis C Virus-infected Cirrhosis

Keywords

Hepatitis C virus, cirrhosis

Outcome Measures

Primary Outcomes (1)

• Adverse events and adverse drug reactions (including subjective symptoms and abnormal laboratory values)

  Items and ratio%

  12 weeks after the initiation of PRI-724 administration

Secondary Outcomes (8)

• Child-Pugh Score

  12 weeks after the initiation of PRI-724 administration

• Liver biopsy: Histology Activity Index (HAI)

  12 weeks after the initiation of PRI-724 administration

• Serum albumin level

  12 weeks after the initiation of PRI-724 administration

• Serum fibrosis marker level(s)

  12 weeks after the initiation of PRI-724 administration

• Ascitic fluid level

  12 weeks after the initiation of PRI-724 administration

Study Arms (1)

PRI-724

EXPERIMENTAL

3 cohorts (PRI-724: 10, 40, 160 mg/m2/day), 6 cycles (1 cycle: 1-week continuous i.v. administration+1-week observation period) \*Cycle 2 will not be started until plasma drug concentrations of PRI-724 and C-82 on Days 1 and 2 in Cycle 1 are confirmed. Cohort 1: 10 mg/m2/day (6 subjects) Cohort 2: 40 mg/m2/day (6 subjects) Cohort 3: 160 mg/m2/day (6 subjects) One cycle consists of 1-week continuous i.v. administration of PRI-724 followed by a 1-week observation period. The tolerability and safety after 6 cycles will be confirmed.

Drug: PRI-724

Interventions

PRI-724 DRUG

10 - 160 mg/m2, 7 days CIV (in the vein) with 7 days rest per one cycle. Number of Cycles: 6.

Also known as: CBP-beta-catennin inhibitor, OP-724

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:

• Presence of cirrhosis due to hepatitis C virus. 1) Serum HCV-RNA test positive 2) Definitive diagnosis of cirrhosis established by liver biopsy (HAI score: Grade IV-D).
• Child-Pugh Class A or B at the time of informed consent, with no likelihood of improvement with existing medical treatment.
• Performance Status: 0 - 2.
• Between =\>20 and \<75 years of age at the time of providing written consent.
• Having provided voluntary written consent for participation in this study.
• Esophageal and gastric varices are well controlled

You may not qualify if:

• Patients with cirrhosis due to causes other than hepatitis C virus; or patients with cirrhosis due to unknown causes.
• Patients with a history of primary liver cancer or a complication thereof.
• Patients with a complication of malignant tumor or a history thereof (within 5 years prior to screening).
• Patients in whom such active viral infections as HBV, HIV or ATCL or syphilis infection cannot be ruled out.
• Patients with serum creatinine \>1.5 times over upper normal or creatinine clearance =\<60 mL/min/1.73 m2.
• Patients with hemoglobin \<8 g/dL.
• Patients with platelet count \<50,000 /\&micro;L.
• Patients with T.Bil =\>3.0 mg/dL.
• Patients with a complication of poorly controlled diabetes, hypertension or heart failure.
• Patients with a complication of mental disorder requiring treatment.
• Patients with serious allergy to contrast media or a history thereof.
• Patients with allergy to inactive ingredients of the study drug.
• Patients who have received interferon, ribavirin or anti-HCV agents within 12 weeks before registration in this study.
• When the medical treatment to a primary disease is carried out, Patient who was changed the dosage and administration within the 12 weeks before registration.
• Patients with a history of drug or alcohol addiction within five years at the time of providing written consent or a history of drug or alcohol abuse within the past one year.

Sponsors & Collaborators

• Komagome Hospital: lead
• Prism Pharma Co., Ltd.: collaborator
• Japan Agency for Medical Research and Development: collaborator

Study Sites (1)

Tokyo metropolitan Komagome Hospital

Tokyo, Japan

Location

Related Publications (1)

• Kimura K, Ikoma A, Shibakawa M, Shimoda S, Harada K, Saio M, Imamura J, Osawa Y, Kimura M, Nishikawa K, Okusaka T, Morita S, Inoue K, Kanto T, Todaka K, Nakanishi Y, Kohara M, Mizokami M. Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/beta-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial. EBioMedicine. 2017 Sep;23:79-87. doi: 10.1016/j.ebiom.2017.08.016. Epub 2017 Aug 19.

  PMID: 28844410 DERIVED

MeSH Terms

Conditions

Hepatitis C; Fibrosis

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kiminori Kimura, MD

  Komagome Metropolitan 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: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 8, 2014
• First Posted: July 21, 2014
• Study Start: August 1, 2014
• Primary Completion: March 31, 2017
• Study Completion: March 31, 2017
• Last Updated: July 7, 2022

Record last verified: 2022-07

Locations

JP (1)