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

Kiminori Kimura, MD

Status and phase: Completed; Phase 2; Phase 1

Conditions: Liver Cirrhoses; Hepatitis C; Hepatitis B

Treatments: Drug: PRI-724

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03620474

UMIN000033369 (Registry Identifier)

PRI-724-2101

Details and patient eligibility

About

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

Full description

【Phase I Phase】 To evaluate safety and pharmacokinetics when PRI-724 is administered to patients with HCV or HBV liver cirrhosis , and determine the recommended dose of PRI-724.

【Phase IIa phase】 To evaluate the efficacy and safety of the recommended dose of PRI-724 administered to patients with HCV or HBV liver cirrhosis.

Enrollment: 27 patients

Sex: All

Ages: 20 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with liver cirrhosis caused by HCV or HBV that satisfies the following (1) or (2) and satisfies (3)

  1. Patients with serum HCV-RNA positive or HCV antibody positive
  2. Patients with serum HBV-DNA positive or HBs antigen positive
  3. 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;

  1. Patients who have not reached SVR * with DAA therapy
  2. Patients who are difficult to implement DAA therapy
  3. Patients who have been over 24 weeks after achieving SVR * with DAA therapy In case of HBV cirrhosis;
  4. 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

Exclusion criteria

• 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.

  • 12 weeks after the final administration of interferon
  • 16 weeks after final administration of Ribavirin
  • 16 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

• Patients who participated in other clinical trials and clinical trials within 30 days prior to acquisition of consent, patients who used investigational drugs or investigational equipment

• Patients who received liver transplantation or other organ transplantation (including bone marrow transplantation) and patients who are difficult to intravenously administer

• Patients whose liver biopsy is expected to be difficult to perform

• Patients who are pregnant or nursing, or who are likely to become pregnant

• Male patients who do not obtain consent to contraception from the time of acquiring informed consent until the end of 12 weeks after the administration of investigational drug

• In addition, patients investigated by investigators or clinical trial doctors as judged unsuitable for this trial

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

27 participants in 1 patient group

PRI-724

Experimental group

Description:

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.

Treatment:

Drug: PRI-724