A Prospective, Randomized, Open-label Study Evaluating the Viral Kinetics and Pharmacokinetics of Pegasys® Plus Copegus® and PEG-Intron® Plus Rebetol® in Interferon-naïve Patients With Chronic Hepatitis C.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 385
- 主要终点
- Change From Baseline in Viral Load (log10 Reduction) at Week 12
研究概览
简要总结
This study will examine the viral kinetics and pharmacokinetics of Pegasys plus ribavirin and PEG-Intron plus ribavirin in interferon-naive patients with CHC. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
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
- None
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
- •adult patients at least 18 years of age
- •CHC infection, genotype 1
- •use of 2 forms of contraception during study in both men and women
排除标准
- •previous systemic therapy with anti-viral, anti-neoplastic, or immunomodulatory agents
- •medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposure)
- •decompensated liver disease
- •women who are pregnant or breastfeeding
研究组 & 干预措施
Peginterferon Alfa-2a + Ribavirin
Participants received Peginterferon alfa-2a (40 kD) [Pegasys] at a dosage of 180 microgram (μg), subcutaneously (SC), once a week plus Ribavirin [Copegus] 1000 or 1200 milligram (mg)/day), orally, [according to body weight, lesser than or greater than/equal to (< or >/=) 75 kilogram (kg), respectively] twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (< or >/=75 kg body weight, respectively twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
干预措施: Ribavirin (Drug)
Peginterferon Alfa-2a + Ribavirin
Participants received Peginterferon alfa-2a (40 kD) [Pegasys] at a dosage of 180 microgram (μg), subcutaneously (SC), once a week plus Ribavirin [Copegus] 1000 or 1200 milligram (mg)/day), orally, [according to body weight, lesser than or greater than/equal to (< or >/=) 75 kilogram (kg), respectively] twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (< or >/=75 kg body weight, respectively twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
干预措施: Peginterferon alfa-2a [Pegasys] (Drug)
Peginterferon Alfa-2b + Ribavirin
Participants received Peginterferon alfa-2b (12 kD) [PEG-Intron] at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin [Rebetol] 1000 or 1200 mg/day orally (< or >/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (< or >/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
干预措施: Peginterferon alfa-2b (PEG-Intron) (Drug)
Peginterferon Alfa-2b + Ribavirin
Participants received Peginterferon alfa-2b (12 kD) [PEG-Intron] at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin [Rebetol] 1000 or 1200 mg/day orally (< or >/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (< or >/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
干预措施: Ribavirin (Drug)
结局指标
主要结局
Change From Baseline in Viral Load (log10 Reduction) at Week 12
时间窗: From Baseline to Week 12
The viral load was determined quantitatively and qualitatively by Hepatitis C virus (HCV)-polymerase chain reaction (PCR). HCV RNA was measured qualitatively using the Roche amplicor PCR assay (lower limit of detection 60 international units per milliliter (U/mL), changed from 50 IU/mL with amendment B) and quantitatively using the Roche amplicor HCV monitor® test v2.0 (lower limit of quantification 600 IU/mL). Log transformations were performed for HCV RNA, and the analyses were done on a log10 scale. The average value of the difference between viral load levels in the serum from baseline to Week 12, expressed in terms of a logarithmic scale with base 10, are presented.
次要结局
- Weekly Viral Load Assessed at Drug Trough(Baseline, up to Week 12)
- Weekly Viral Absolute Area Under the HCV RNA Curve Estimated in the Frequent-sampling Cohort for Weeks 1 and 8(Week 1 and Week 8)
- Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit(From Week 1 to Week 12)
- Percentage of Participants With Each of the Identified HCV Quasispecies at Baseline and Weeks 1, 4, 8, and 12(Baseline, Weeks 1, 4,8, and 12)
- Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit(From Week 1 to Week 12)
- Number of Participants With Marked Hematologic Abnormalities(Baseline, up to Week 12)
- Mean Trough Interferon Concentrations at Each Week(From Week 1 to Week 12)
- Weekly AUC for IFN Concentrations for Pegasys and PEG-Intron Estimated by Population Pharmacokinetic Modeling(Up to Week 8)
- Mean Change From Baseline in Viral Load (log10 Reduction) at Week 4 and Week 8(Baseline, Week 4 and Week 8)
- The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week(From Week -1 to Week 12)
- Cumulative Viral Absolute Area Under the HCV RNA Curve Minus Baseline Averaged Over the 12-week Period(Up to Week 12)
- Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12(Baseline, Week 1 to Week 12)
- Number of Participants With Marked Biochemical Test Abnormalities(Baseline, up to Week 12)
- Number of Participants With Marked Abnormalities in Thyroid Function Tests(Baseline, up to Week 12)
- Area Under the Curve for Interferon in the Frequent-Sampling Cohort(Week 1 and Week 8)
- Number of Participants With Adverse Events and Serious Adverse Events(Up to Week 12)