Safety and Tolerability Study of OP-724 in Liver Cirrhosis Patients by HIV/HCV with Hemophilia.

NCT04688034 | Completed Phase 1 DMC

• 2 other identifiers: OP-724-H101jRCT2031200266
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of OP-724 in liver cirrhosis patients caused by HIV/HCV co-infection with hemophilia.

Conditions

Liver Cirrhosis

Keywords

Liver Cirrhosis; Hemophilia; HIV/HCV co-infection

Outcome Measures

Primary Outcomes (1)

• Serious Adverse Events (Side Effects)

  Occurrence rate of serious adverse events whose causal relationship with the investigational drug cannot be ruled out (side effects). The data will be aggregated by each cohort.

  28 days after the last administration of OP-724.

Secondary Outcomes (15)

• Adverse Events

  28 days after the last administration of OP-724.

• Side Effects

  28 days after the last administration of OP-724.

• Parameters on Pharmacokinetics (OP-724 and C-82): Maximum Plasma Concentration (Cmax)

  Single administration part: pre-dose and post-dose at 0.5, 1, 2, 4, 5, 9 and 24 hours.

• Parameters on Pharmacokinetics (OP-724 and C-82): Area Under the Curve from 0 to 24 hours (AUC0-24h)

  Single administration part: pre-dose and post-dose at 0.5, 1, 2, 4, 5, 9 and 24 hours.

• Parameters on Pharmacokinetics (OP-724 and C-82): Time to Maximum Plasma Concentration (Tmax)

  Single administration part: pre-dose and post-dose at 0.5, 1, 2, 4, 5, 9 and 24 hours.

Study Arms (1)

OP-724 400 mg / 20 mL / vial (20 mg / mL)

EXPERIMENTAL

Dose: \[Cohort 1\] 140 mg/m2/4 hours (starting dose) , \[Cohort 2\] 280 mg/m2/4 hours Administration method: In the single administration, the safety of concomitant use with the investigational drug and antiretroviral drug will be confirmed and then the cycle administration will be started. For the single administration, at 14 days before the first cycle of administration, the dose planned for the first cycle with continuous intravenous administration for 4 hours will be administrated once. When an integrase inhibitor is used in combination as a key drug for antiretroviral drugs, it should be administered at the same time as the start of investigational drug administration only after the single administration. For the cycle administration, the continuous intravenous administration for 4 hours twice a week is defined as one cycle, and 12 cycles (12 weeks in total) will be performed.

Drug: OP-724

Interventions

OP-724 DRUG

Twice a week for 4 hours continuous intravenous administration of OP-724.

Also known as: CBP-beta-catenin inhibitor, PRI-724 (former name)

OP-724 400 mg / 20 mL / vial (20 mg / mL)

Eligibility Criteria

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

You may qualify if:

• \. Hemophilia patients with liver cirrhosis caused by HIV/HCV co-infection that fall under the following 1) and 2).
• HIV-RNA positive in serum or HIV antibody positive patients (the amount of HIV-RNA in the blood at the time of screening is less than 200 copies/mL, and the number of CD4 positive T lymphocytes can be maintained at 200/micro L or more).
• HCV-RNA positive in serum or HCV antibody positive patients (regardless of the amount of viral and treatment).
• \. Patients with Child-Pugh class A or B.
• \. Patients who meet at least one of 1) to 3) for diagnosis of liver cirrhosis.
• FIB-4 index value is 3.25 or higher.
• Liver hardness value by FibroScan is 11.8 kPa or more.
• Abdominal CT scan shows changes in liver shape and/or portal hypertension symptoms.
• \. Patients who meet any of 1) to 3) for anti-HCV therapy.
• Patients who have not reached the sustained virological response (SVR) \* with the direct acting antivirals (DAA) therapy. \* SVR shall be as SVR12 (persistent virus negative at 12 weeks after the end of administration).
• Patients who have difficulty in performing DAA therapy.
• Patients who have passed 24 weeks or more after achieving SVR\* with DAA therapy or IFN therapy.
• \. Patients with Performance Status 0-2.
• \. Male patients aged 20 to under 75 at the time of obtaining written consent.
• \. Patients who provided voluntary written consent to participate in this clinical trial.

You may not qualify if:

• Patients who have cirrhosis due to causes other than HCV, and patients whose cause of cirrhosis is unknown.
• Patients with esophagogastric varices who are judged to require treatment by endoscopy at the time of screening.
• Patients with complication or with previous history of primary liver cancer (excluding patients who have been for more than 1 year after hepatoma removing operation or radiofrequency ablation etc.).
• Patients with complication or with previous history of malignant tumor (within 3 years before screening).However, except for the following diseases: treated basal cell carcinoma, treated lung carcinoma in situ, or well-controlled superficial (non-invasive) bladder cancer.
• Patients with active AIDS index disease requiring treatment.
• Patients for whom HBV, HTLV-1 active viral infection or syphilis infection cannot be ruled out.
• Serum creatinine level: Patients over 1.5 times the upper limit of the facility reference value.
• Patients with complications with uncontrolled diabetes, hypertension or heart failure.
• Patients with psychiatric disorders that may affect the conduct of clinical trial.
• Patients with or have a history of serious allergies to contrast agent.
• Patients who have not passed the following period at the time of registration and after the end of anti-HCV therapy.
• IFN preparation 12 weeks after the last administration
• Ribavirin preparation 16 weeks after the last administration
• weeks after the last administration of DAA
• Patients whose dosage and administration have been changed within 12 weeks prior to registration if the following treatments have been given.

Sponsors & Collaborators

• Kiminori Kimura, MD: lead
• Japan Agency for Medical Research and Development: collaborator
• Ohara Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Tokyo Metropolitan Komagome Hospital

Bunkyo-Ku, Tokyo, 113-8677, Japan

Location

Related Publications (1)

• Kimura K, Tanuma J, Kimura M, Imamura J, Yanase M, Ieiri I, Kurosaki M, Watanabe T, Endo T, Yotsuyanagi H, Gatanaga H. Safety and tolerability of OP-724 in patients with haemophilia and liver cirrhosis due to HIV/HCV coinfection: an investigator-initiated, open-label, non-randomised, single-centre, phase I study. BMJ Open Gastroenterol. 2024 Apr 27;11(1):e001341. doi: 10.1136/bmjgast-2023-001341.

  PMID: 38677720 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis; Hemophilia A

Interventions

ICG 001

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Kiminori Kimura, MD

  Tokyo Metropolitan 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: December 21, 2020
• First Posted: December 29, 2020
• Study Start: March 15, 2021
• Primary Completion: July 5, 2022
• Study Completion: July 5, 2022
• Last Updated: October 21, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)