Phase I / IIa Clinical Trial for Patients With Hepatitis C or B Virus Derived Liver Cirrhosis by CBP / β Catenin Inhibitor PRI-724
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 3
- 主要终点
- Serious side effect expression rate
研究概览
简要总结
To investigate the safety and efficacy of PRI-724 against HCV or HBV liver cirrhosis.
详细描述
【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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with liver cirrhosis caused by HCV or HBV that satisfies the following (1) or (2) and satisfies (3)
- •Patients with serum HCV-RNA positive or HCV antibody positive
- •Patients with serum HBV-DNA positive or HBs antigen positive
- •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;
- •Patients who have not reached SVR * with DAA therapy
- •Patients who are difficult to implement DAA therapy
- •Patients who have been over 24 weeks after achieving SVR * with DAA therapy In case of HBV cirrhosis;
- •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
排除标准
- •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
研究组 & 干预措施
PRI-724
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.
干预措施: PRI-724 (Drug)
结局指标
主要结局
Serious side effect expression rate
时间窗: 12 weeks after administration
(Phase I)Serious side effect expression rate
liver tissue fibrosis area ratio by liver biopsy
时间窗: 12 weeks after administration
(Phase II) Amount of change from the baseline in liver tissue fibrosis area ratio by liver biopsy at 12 weeks after administration
次要结局
- Adverse Event Expression Ratio(12 weeks after administration)
- Percentage of occurrence of side effects(12 weeks after administration)
- Pharmacokinetic parameter(12 weeks after administration)
- liver stiffness from Fibro Scan(12 weeks after administration)
- Child Pugh score(12 weeks after administration)
- MELD score(12 weeks after administration)
- modified Histological Activity Index (HAI) by liver biopsy(12 weeks after administration)
研究者
Kiminori Kimura, MD
Head, Department of Hepatology
Komagome Hospital