A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Safety And Efficacy Of Filibuvir Plus Pegylated Interferon Alfa-2a And Ribavirin In Treatment-Naive, HCV Genotype 1 Infected Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 288
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Sustained Viral Response (SVR) at Week 72
研究概览
简要总结
The primary objective for this study is to determine if the addition of filibuvir to a standard regimen of peginterferon/ribavirin (pegIFN/RBV) significantly increases the proportion of subjects who achieve a sustained viral response (SVR) compared to peginterferon/ribavirin (pegIFN/RBV) therapy alone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects at least 18 years of age.
- •HCV seropositive.
- •HCV RNA >10,000 IU/mL at screening.
- •HCV Genotype
- •Subjects infected with a non-genotype 1 strain or mixed genotypes are not eligible.
- •Treatment naïve (no prior treatment with IFN alfa +/ RBV regimens or investigational anti-HCV agents).
- •Liver biopsy within two years (24 months) of Screening with non-cirrhotic fibrosis classification. For those subjects with liver biopsy outside of the time window or for those subjects with no history of liver biopsy, a biopsy must be performed prior to randomization.
- •Ultrasound within 6 months of Screening for 1) those subjects with bridging fibrosis or 2) those subjects with AFP >50 and <100 ng/mL with no evidence of hepatocellular carcinoma. For those subjects with an ultrasound conducted outside the 6-month time window, an ultrasound must be performed prior to randomization.
排除标准
- •Co-infection with either HIV or HBV.
- •Evidence of severe or decompensated liver disease.
- •Subjects with liver disease unrelated to HCV infection.
- •Pre-existing medical condition that makes the subject unsuitable for treatment with pegIFN/RBV therapy per product labeling.
- •Laboratory abnormality at Screening that makes the subject unsuitable for treatment with pegIFN/RBV therapy per product labeling.
- •Abnormal ECG suggestive of clinically significant cardiac disease or QTc>450msec.
- •History of organ transplant.
- •Contraindicated medications being taken by the subject at the time of randomization that must be continued during the study period, including potent CYP3A4 inhibitors, sensitive CYP3A4 substrates, CYP3A4 substrates with narrow therapeutic range and CYP3A4 inducers.
- •Active alcohol or substance abuse sufficient, in the Investigator's judgment, to prevent adherence to study medication and/or follow up.
- •Pregnant or nursing females.
- •Males whose female partner is pregnant.
研究组 & 干预措施
Arm A
Filibuvir 300 mg BID + pegIFN/RBV x 24 weeks (subjects with undetectable HCV RNA at week 4)
- or - Filibuvir 300 mg BID + pegIFN/RBV x 24 weeks followed by pegIFN/RBV x 24 weeks (subjects with detectable HCV RNA at week 4)
干预措施: Filibuvir (Drug)
Arm B
Filibuvir 600 mg BID + pegIFN/RBV x 24 weeks (subjects with undetectable HCV RNA at week 4)
- or - Filibuvir 600 mg BID + pegIFN/RBV x 24 weeks followed by pegIFN/RBV x 24 weeks (subjects with detectable HCV RNA at week 4)
干预措施: Filibuvir (Drug)
Arm C
Placebo + pegIFN/RBV x 24 weeks followed by pegIFN/RBV x 24 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Viral Response (SVR) at Week 72
时间窗: Week 72
For participants who received filibuvir, had undetectable HCV RNA from Week 4 through 24 and discontinued therapy at Week 24, SVR was defined as undetectable plasma HCV RNA levels (\<15 IU/mL) at both Week 24 (End of Treatment \[EOT\]) and Week 72, regardless of the HCV RNA levels between Week 24 and 72. For participants who received filibuvir, had detectable HCV RNA at Week 4 or later and discontinued therapy at Week 48 or who received placebo, SVR was defined as undetectable plasma HCV RNA levels (\<15 IU/mL) at both Week 48 (EOT) and Week 72, regardless of the HCV RNA levels between Week 48 and 72.
次要结局
- Percentage of Participants With Sustained Viral Response at 24 Weeks Following Completion of Therapy (SVR24)(24 weeks after completion of therapy (Week 48 or 72))
- Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4, 12 and 24(Baseline, Week 4, 12, 24)
- Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4, 12, 24 and 48(Week 4, 12, 24, 48)
- Percentage of Participants With Sustained Viral Response at 12 Weeks Following Completion of Therapy (SVR12)(12 weeks after completion of therapy (Week 36 or 60))
- Percentage of Participants With Breakthrough Viremia(Baseline up to Week 48)
- Percentage of Participants With Relapsed Response(Week 24 or Week 48 up to Week 72)
- Number of Adverse Events (AEs) by Severity (All Causality)(Baseline up to Week 72)
- Plasma Concentration of Filibuvir, Pegylated Interferon and Ribavirin(Week 0 (pre-dose), Week 2, 4, 8, 12, 16, 20, 24, 48 (only for those participants who received treatment till Week 48) post-dose)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Relationship to Study Drug (Any Therapy)(Baseline up to Week 72)
- Number of Participants Who Discontinued Study Due to Adverse Events (AEs)(Baseline up to Week 72)
- Number of Participants With Dose Reduction or Temporary Discontinuation Due to Adverse Events (AEs)(Baseline up to Week 72)
- Number of Participants With Laboratory Test Abnormalities by Severity(Baseline up to Week 72)