Safety and tolerability study of OP-724 in liver cirrhosis patients by HIV/HCV with hemophilia. (Phase I).

JRCT ID: jRCT2031200266

Registered date:24/12/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Liver cirrhosis caused by HIV/HCV co-infected with hemophilia
• Date of first enrollment: 15/03/2021
• Target sample size: 6
• Study type: Interventional

Intervention(s)

Experimental:
OP-724 400 mg / 20 mL / vial (20 mg / mL)
Dose:
[Cohort 1] 140 mg/m2/4 hours
[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 hourswill 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 aweek is defined as one cycle, and 12 cycles (12 weeks in total) will be
performed.

Outcome(s)

• Primary Outcome: Occurrence rate of serious adverse events whose causal relationship with the investigational drug cannot be ruled out (side effects)

Secondary Outcome

(1) Occurrence rate of adverse events.
(2) Occurrence rate of side effects .
(3) Pharmacokinetics (OP-724 and C-82).
(4) Pharmacokinetics (Integrase inhibitor).
(5) Amount of change in blood HIV-RNA level from baseline at each measurement
time point.
(6) Amount of change in CD4 positive T lymphocyte count from baseline at each
measurement time point.
(7) Amount of change from baseline in the measured value of liver tissue hardness
by Fibro Scan at 12 weeks after administration.
(8) Amount of change from baseline in FIB-4 index at 12 weeks after administration.
(9) Amount of change from baseline in APRI at 12 weeks after administration.
(10) Amount of change from baseline in Child-Pugh Score at 12 weeks after
administration.
(11) Amount of change from baseline in MELD score at 12 weeks after administration.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 75age old
• Gender: Male

Include criteria

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

Exclude criteria

(1) Patients who have cirrhosis due to causes other than HCV, and patients whose
cause of cirrhosis is unknown.
(2) Patients with esophagogastric varices who are judged to require treatment by
endoscopy at the time of screening.
(3) Patients with complications or with previous history of primary liver cancer
(excluding patients who have been ablated for liver cancer for more than 1 year after
hepatoma removing operation or radiofrequency ablation etc.).
(4) Patients with complications 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.
(5) Patients with active AIDS index disease requiring treatment.
(6) Patients for whom HBV, HTLV-1 active viral infection or syphilis infection cannot be ruled out.
(7) Serum creatinine level: Patients over 1.5 times the upper limit of the facility
reference value.
(8) Patients with complications with uncontrolled diabetes, hypertension or heart
failure.
(9) Patients with psychiatric disorders that may affect the conduct of clinical trial.
(10) Patients with or have a history of serious allergies to contrast agent.
(11) 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
- 16 weeks after the last administration of DAA
(12) Patients whose dosage and administration have been changed within 12 weeks prior to registration if the following treatments have been given.
- Liver cirrhosis
- HIV
(13) Patients with a history of drug or alcohol intoxication within 5 years prior to obtaining written consent, or patients with a history of drug or alcohol abuse within the last 1 year.
(14) Patients who participated in other clinical trials within 30 days before obtaining
written consent and used or used investigational drugs or investigational medical
devices.
(15) Patients who have undergone liver transplantation or other organ transplantation (including bone marrow transplantation) and patients who have difficulty in
intravenous administration.
(16) Male patients who do not consent to contraception from the time of consent
acquisition to 12 weeks after the end of study drug administration.
(17) In addition, patients who are judged by the investigator or sub-investigator to be ineligible for this study.

Related Information

• Primary Sponsor: Kimura Kiminori
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development
• Secondary ID(s): NCT04688034