A Phase 2, Open-Label Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Activity of a Titrating-Dose Lonafarnib/Ritonavir in Patients Chronically Infected With Hepatitis Delta Virus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 主要终点
- Change From Baseline to Week 24 in Mean Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) Titer
研究概览
简要总结
A phase 2, open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of titrating-dose lonafarnib/ritonavir in patients chronically infected with hepatitis delta virus (HDV)
详细描述
This is a Phase 2 study of 24 weeks of treatment with a dose-titration regimen of lonafarnib/ritonavir in up to 15 patients chronically infected with HDV: lonafarnib starting at 50 mg twice daily (BID) in combination with ritonavir 100 mg BID and escalating lonafarnib as tolerated.
The duration of the study for each patient is approximately 13 months (up to 4 weeks for screening, 24 weeks of treatment, 4 weeks for the primary follow-up visit, and monthly safety follow-up visits for 5 months thereafter). The 6-month follow-up after the last dose of study drug is designed to allow evaluation of the clinical and virologic course after completion of the 24-week Treatment Period.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 18 to 65 years of age, inclusive
- •Chronic HDV infection documented by a positive HDV antibody (Ab) test of at least 6 months duration and detectable HDV ribonucleic acid (RNA) by quantitative polymerase chain reaction (qPCR) at study entry
- •Liver biopsy demonstrating evidence of chronic hepatitis
- •Willingness to practice appropriate contraception
排除标准
- •Previous use of lonafarnib
- •Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)
- •Active jaundice defined by total bilirubin level >2.0 mg/dL and known not to have Gilbert's disease
- •Decompensated liver disease or cirrhosis, history of bleeding esophageal varices, ascites, or hepatic encephalopathy
- •Serum creatinine concentration ≥1.5 times upper limit of normal (ULN)
- •Evidence of another form of viral hepatitis (not including hepatitis B virus or HCV) or another form of liver disease
- •Evidence of hepatocellular carcinoma
- •Use of alfa interferon, either interferon alfa-2a or interferon alfa-2b, or peginterferon alfa-2a within 2 months before the start of screening
- •Concomitant use of any of the following:
- •Medications or foods that are known moderate or strong inducers or inhibitors of CYP3A4 or CYP2C19
- •Drugs known to prolong the PR interval or QT interval of the electrocardiogram
- •Receipt of systemic immunosuppressive therapy within the 3 months before start of screening
- •Statins, due to inhibition of mevalonate synthesis, which reduces protein prenylation
- •Medications contraindicated in the prescribing information for ritonavir
研究组 & 干预措施
lonafarnib/ritonavir
Lonafarnib starting at 50 mg BID in combination with ritonavir 100 mg BID and escalating to lonafarnib 75 mg BID and then 100 mg BID as tolerated. The duration of the study for each patient is 6 months of treatment and 6 months follow-up.
干预措施: lonafarnib (Drug)
lonafarnib/ritonavir
Lonafarnib starting at 50 mg BID in combination with ritonavir 100 mg BID and escalating to lonafarnib 75 mg BID and then 100 mg BID as tolerated. The duration of the study for each patient is 6 months of treatment and 6 months follow-up.
干预措施: Ritonavir (Drug)
结局指标
主要结局
Change From Baseline to Week 24 in Mean Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) Titer
时间窗: Baseline and Week 24 (6 months)
Change from baseline to Week 24 in mean HDV RNA titer following dose escalating from lonafarnib 50 mg BID to 75 mg BID and to 100 mg BID, all boosted with ritonavir 100 mg BID.
次要结局
- Number of Patients With 1 Log Reduction From Baseline by Timepoint(Baseline and Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, or Week 24)