To evaluate the safety and tolerability of OP-724 in liver cirrhosis patients caused by HIV/HCV co-infection with hemophilia.
This trial is an uncontrolled, open-label, single-center phase I study in liver cirrhosis patients caused by human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection with hemophilia. Liver cirrhosis patients due to co-infection of HIV and HCV with hemophilia who have a Child-Pugh classification of A or B are included. OP-724 is intravenously administered twice a week (4 hours) for 12 weeks as an administration schedule. At 14 days before the administration of the first cycle, the dose planned for the first cycle will be administered once by continuous intravenous administration for 4 hours, and the safety and pharmacokinetics will be evaluated from the day of administration to the day after the administration. If an integrase inhibitor is used in combination as a key drug for antiretroviral drugs, its pharmacokinetics will be evaluated at the same time. A dose escalation study with 2 doses (cohort 1: 140 mg/m2/4hr (starting dose), cohort 2: 280 mg/m2/4hr) will be conducted, and 3 patients in each cohort will be enrolled. Comprehensively investigate the safety and pharmacokinetic data after OP-724 administration, and evaluate the safety and tolerability of OP-724 administration.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Twice a week for 4 hours continuous intravenous administration of OP-724.
Tokyo Metropolitan Komagome Hospital
Bunkyo-Ku, Tokyo, Japan
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.
Time frame: 28 days after the last administration of OP-724.
Adverse Events
Occurrence rate of adverse events. The data will be aggregated by each cohort, seriousness and severity.
Time frame: 28 days after the last administration of OP-724.
Side Effects
Occurrence rate of side effects.
Time frame: 28 days after the last administration of OP-724.
Parameters on Pharmacokinetics (OP-724 and C-82): Maximum Plasma Concentration (Cmax)
Cmax of OP-724 and C-82 will be determined.
Time frame: 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)
AUC0-24 of OP-724 and C-82 will be determined.
Time frame: 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)
Tmax of OP-724 and C-82 will be determined.
Time frame: 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): t1/2
t1/2 of OP-724 and C-82 will be determined.
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Time frame: Single administration part: pre-dose and post-dose at 0.5, 1, 2, 4, 5, 9 and 24 hours.
Drug Concentration (OP-724 and C-82) in Plasma
Graphing with time course of drug concentration.
Time frame: A) Single administration part: pre-dose and post-dose at 0.5, 1, 2, 4, 5, 9 and 24 hours. B) Continuous administration part: pre-dose and post-dose at 4 hours on Day 1 and 4 in Cycle 1, 5, 9 and 12 (each cycle is 7days).
Drug Concentration (Integrase inhibitor) in Plasma
Graphing with time course of drug concentration.
Time frame: A) Single administration part: pre-dose and post-dose at 2, 4, 9 and 24 hours. B) Continuous administration part: pre-dose on Day 1 in Cycle 5, 9 and 12 (each cycle is 7days).
Blood HIV-RNA Level
Amount of change in blood HIV-RNA level from baseline at each measurement time point.
Time frame: Baseline, Cycle5Day1, Cycle9Day1 and up to 12 weeks after administration (each cycle is 7days).
CD4 Positive T Lymphocyte Count
Amount of change in CD4 positive T lymphocyte count from baseline at each measurement time point.
Time frame: Baseline, Cycle5Day1, Cycle9Day1 and up to 12 weeks after administration (each cycle is 7days).
FibroScan
Amount of change from baseline in the measured value of liver tissue hardness by FibroScan at 12 weeks after administration.
Time frame: Baseline and 12 weeks after administration
FIB-4 Index
Amount of change from baseline in FIB-4 index at 12 weeks after administration.
Time frame: Baseline and 12 weeks after administration
APRI
Amount of change from baseline in APRI at 12 weeks after administration.
Time frame: Baseline and 12 weeks after administration
Child-Pugh Score
Amount of change from baseline in Child-Pugh Score at 12 weeks after administration. Child Pugh score (scale range 5-15 points, the severity increases sequentially from 5 to 15 points) is obtained by adding the score for each parameter (hepatic encephalopathy, ascites, bilirubin, albumin, PT). Based on the total points score (Child-Pugh Score) of each diagnostic parameter shown above, the severity of the disease is classified into Grades A to C shown below. * Grade A: 5-6 points -\> Compensated cirrhosis * Grade B: 7-9 points -\> Decompensated cirrhosis * Grade C: 10-15 points -\> Decompensated cirrhosis
Time frame: Baseline and 12 weeks after administration
MELD Score
Amount of change from baseline in 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 score = 3.78×ln\[serum bilirubin (mg/dL)\] + 11.2×ln\[INR\] + 9.57×ln\[serum creatinine (mg/dL)\] + 6.43
Time frame: Baseline and 12 weeks after administration