An Open Label, Single Arm, Dose Escalation Phase 1 Trial of PRI-724 in Patients With HCV-induced Cirrhosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Adverse events and adverse drug reactions (including subjective symptoms and abnormal laboratory values)
研究概览
简要总结
The purpose of this study is to investigate the safety and tolerability of PRI-724 in patients with HCV-induced cirrhosis.
详细描述
This is a single-center, open-label, continuous i.v. administration, dose escalation Phase I study in patients with hepatitis C cirrhosis.
One cycle consisted of one-week continuous i.v. administration of PRI-724 followed by a one-week observation period. One cohort was a total of six cycles, a 12-week treatment period.
PRI-724 was administered at a dose of 10 mg/m2/day in Cohort 1, 40 mg/m2/day in Cohort 2, and 160 mg/m2/day in Cohort 3 in a dose escalation manner. Each cohort was to include 6 subjects.
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
- •Presence of cirrhosis due to hepatitis C virus. 1) Serum HCV-RNA test positive 2) Definitive diagnosis of cirrhosis established by liver biopsy (HAI score: Grade IV-D).
- •Child-Pugh Class A or B at the time of informed consent, with no likelihood of improvement with existing medical treatment.
- •Performance Status: 0 -
- •Between =>20 and <75 years of age at the time of providing written consent.
- •Having provided voluntary written consent for participation in this study.
- •Esophageal and gastric varices are well controlled
排除标准
- •Patients with cirrhosis due to causes other than hepatitis C virus; or patients with cirrhosis due to unknown causes.
- •Patients with a history of primary liver cancer or a complication thereof.
- •Patients with a complication of malignant tumor or a history thereof (within 5 years prior to screening).
- •Patients in whom such active viral infections as HBV, HIV or ATCL or syphilis infection cannot be ruled out.
- •Patients with serum creatinine >1.5 times over upper normal or creatinine clearance =<60 mL/min/1.73 m
- •Patients with hemoglobin <8 g/dL.
- •Patients with platelet count <50,000 /µL.
- •Patients with T.Bil =>3.0 mg/dL.
- •Patients with a complication of poorly controlled diabetes, hypertension or heart failure.
- •Patients with a complication of mental disorder requiring treatment.
- •Patients with serious allergy to contrast media or a history thereof.
- •Patients with allergy to inactive ingredients of the study drug.
- •Patients who have received interferon, ribavirin or anti-HCV agents within 12 weeks before registration in this study.
- •When the medical treatment to a primary disease is carried out, Patient who was changed the dosage and administration within the 12 weeks before registration.
- •Patients with a history of drug or alcohol addiction within five years at the time of providing written consent or a history of drug or alcohol abuse within the past one year.
- •The patient who received a liver transplant or other organ transplants (a bone marrow transplantation is included), and the patient for whom intravenous administration and venous access are difficult.
- •Patients contraindicated for liver biopsy.
- •Female patients who are pregnant or suspected to be pregnant; or those who desire to get pregnant during the study period or those of childbearing potential.
- •Male patients who do not consent to practice birth control during the clinical study.
研究组 & 干预措施
PRI-724
3 cohorts (PRI-724: 10, 40, 160 mg/m2/day), 6 cycles (1 cycle: 1-week continuous i.v. administration+1-week observation period)
*Cycle 2 will not be started until plasma drug concentrations of PRI-724 and C-82 on Days 1 and 2 in Cycle 1 are confirmed.
Cohort 1: 10 mg/m2/day (6 subjects) Cohort 2: 40 mg/m2/day (6 subjects) Cohort 3: 160 mg/m2/day (6 subjects) One cycle consists of 1-week continuous i.v. administration of PRI-724 followed by a 1-week observation period. The tolerability and safety after 6 cycles will be confirmed.
干预措施: PRI-724 (Drug)
结局指标
主要结局
Adverse events and adverse drug reactions (including subjective symptoms and abnormal laboratory values)
时间窗: 12 weeks after the initiation of PRI-724 administration
Items and ratio%
次要结局
- Ascitic fluid level(12 weeks after the initiation of PRI-724 administration)
- Improvement rate of lower leg edema(12 weeks after the initiation of PRI-724 administration)
- Assessment of Steady State Plasma Concentration (Css) of PRI-724 through analysis of blood samples(Days 1-2 for preinfusion, 0.5, 1.0, 2.0, 4.0, and 24h; Day 7-8 for prestopping, 0.5, 1.0, 2.0, 4.0, and 24h)
- Assessment of Area under the plasma concentration versus time curve (AUCinf) of PRI-724 through analysis of blood samples(Days 1-2 for preinfusion, 0.5, 1.0, 2.0, 4.0, and 24h; Day 7-8 for prestopping, 0.5, 1.0, 2.0, 4.0, and 24h)
- Child-Pugh Score(12 weeks after the initiation of PRI-724 administration)
- Liver biopsy: Histology Activity Index (HAI)(12 weeks after the initiation of PRI-724 administration)
- Serum albumin level(12 weeks after the initiation of PRI-724 administration)
- Serum fibrosis marker level(s)(12 weeks after the initiation of PRI-724 administration)
研究者
Kiminori Kimura, MD
MD
Komagome Hospital