NCT01519960已完成3 期
A Phase IIIb Parallel Group, Open Label Study of Pegylated Interferon Alfa-2a Monotherapy (PEG-IFN, Ro 25-8310) Compared to Untreated Control in Children With HBeAg Positive Chronic Hepatitis B
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 165
- 试验地点
- 39
- 主要终点
- Percentage of Participants With HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B
研究概览
简要总结
This parallel group, open label study will evaluate the safety and efficacy of Pegasys (peginterferon alfa-2a) versus untreated control in children (age 3 years to <18 years at baseline) with HBeAg positive chronic hepatitis B. Children without advanced fibrosis and without cirrhosis will be randomized 2:1 to treatment Group A, receiving Pegasys 45-180 mcg subcutaneously weekly for 48 weeks, or to the untreated control Group B. Children with advanced fibrosis will be assigned to treatment group C and receive 48 weeks of treatment with Pegasys. Children in the untreated control Group B who have not experienced seroconversion 48 weeks after randomization may enter the Switch Arm to receive 48 weeks of Pegasys treatment. This offer will be available for 1 year following 48 weeks from randomization. Anticipated time on study treatment is 48 weeks. All subjects will be followed up for 5 years after the end of treatment (A,C,Switch)/principal observation (B) period.
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
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients, 3 years to <18 years of age at baseline
- •Positive HBsAg for more than 6 months
- •Positive HBeAg and detectable HBV DNA at screening
- •A liver biopsy obtained within the past 2 years prior to baseline (and more than 6 months after the end of previous therapy for hepatitis B) to confirm the presence of advanced fibrosis or exclude cirrhosis
- •Compensated liver disease (Child-Pugh Class A)
- •Elevated serum alanine transferase (ALT)
- •Normal thyroid gland function at screening
排除标准
- •Subjects with cirrhosis
- •Subjects must not have received investigational drugs or licensed treatments with anti-HBV activity within 6 months of baseline. Subjects who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded
- •Known hypersensitivity to peginterferon
- •Positive test results at screening for hepatitis A, hepatitis C, hepatitis D or HIV infection
- •History or evidence of medical condition associated with chronic liver disease other than chronic hepatitis B
- •History or evidence of bleeding from esophageal varices
- •Decompensated liver disease (e.g. ascites, Child-Pugh Class B or C)
- •History of immunologically mediated disease
- •Pregnant or lactating females
研究组 & 干预措施
C Fibrosis non-randomized
Experimental
干预措施: peginterferon alfa-2a [Pegasys] (Drug)
A Pegasys
Experimental
干预措施: peginterferon alfa-2a [Pegasys] (Drug)
Switch
Experimental
干预措施: peginterferon alfa-2a [Pegasys] (Drug)
结局指标
主要结局
Percentage of Participants With HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B
时间窗: FU Week 24 (up to 72 weeks overall)
HBeAg seroconversion was defined as loss of HBeAg and the presence of hepatitis B envelope antibody (anti-HBe). The percentage of participants with HBeAg seroconversion at 24 weeks after EOT/POP was reported. The 95 percent (%) confidence interval (CI) was calculated by the Pearson-Clopper method. Intent-to-Treat (ITT) Population: All randomized participants regardless of treatment received.
次要结局
- Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at 24 Weeks After EOT/POP in Groups A and B(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT/POP in Groups A and B(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Normal ALT at 24 Weeks After EOT/POP in Groups A and B(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B(Week 48)
- Quantitative HBV DNA Level in Groups A and B(Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall))
- Percentage of Participants With HBeAg Seroconversion at EOT in Group C(Week 48)
- Percentage of Participants With >15% Drop in Weight Percentile for Age in Groups A and B(Weeks 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall))
- Quantitative HBsAg Level in Group C(Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With >15% Drop in Height Percentile for Age in Group C(Weeks 30, 36; FU Weeks 4, 12, 24 (up to 72 weeks overall))
- Change From Baseline in Height for Age Z-Score in Groups A and B(Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall))
- Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) <20,000 International Units Per Milliliter (IU/mL) at 24 Weeks After EOT/POP in Groups A and B(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Loss of HBeAg at EOT/POP in Groups A and B(Week 48)
- Change From Baseline in Quantitative HBV DNA Level in Groups A and B(Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall))
- Percentage of Participants With HBsAg Seroconversion at 24 Weeks After EOT in Group C(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With HBV DNA <2,000 IU/mL at EOT in Group C(Week 48)
- Percentage of Participants With HBV DNA Undetectable at EOT in Group C(Week 48)
- Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT in Group C(Week 48)
- Quantitative Serum ALT Level in Group C(Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall))
- Change From Baseline in Liver Stiffness Measure (LSM) in Groups A, B, C(Week 48; FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With HBsAg Seroconversion at EOT/POP in Groups A and B(Week 48)
- Percentage of Participants With Loss of HBsAg at EOT/POP in Groups A and B(Week 48)
- Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With HBsAg Seroconversion at EOT in Group C(Week 48)
- Change From Baseline in Quantitative HBV DNA Level in Group C(Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall))
- Estimated Area Under the Concentration-Time Curve (AUC) by BSA Category(Pre-dose (0 hours) at Baseline and Weeks 4, 8, 12, 24; post-dose (24-48, 72-96, 168 hours) during Weeks 1, 24 (up to 24 weeks overall))
- Percentage of Participants With >15% Drop in Height Percentile for Age in Groups A and B(Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall))
- Quantitative HBsAg Level in Groups A and B(Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall))
- Change From Baseline in Quantitative HBsAg Level in Group C(Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With HBeAg Seroconversion Over Time in Groups A and B(Baseline, FU Years: 1, 2, 3, 4, 5)
- Percentage of Participants With Loss of HBeAg at 24 Weeks After the End of Switch Treatment Period: Switch Group(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With HBeAg Seroconversion at EOT/POP in Groups A and B(Week 48)
- Percentage of Participants With HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B(Week 48)
- Percentage of Participants With HBV DNA Undetectable at EOT/POP in Groups A and B(Week 48)
- Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B(Week 48)
- Quantitative Serum ALT Level in Groups A and B(Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall))
- Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT in Group C(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Loss of HBsAg at 24 Weeks After EOT in Group C(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Normal ALT at 24 Weeks After EOT in Group C(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Loss of HBeAg at EOT in Group C(Week 48)
- Percentage of Participants With Normal ALT at EOT/POP in Groups A and B(Week 48)
- Percentage of Participants With HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B(Week 48)
- Percentage of Participants With HBV DNA Undetectable at 24 Weeks After EOT in Group C(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Loss of HBsAg at EOT in Group C(Week 48)
- Quantitative HBV DNA Level in Group C(Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall))
- Quantitative HBeAg Level in Groups A and B(Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall))
- Quantitative HBeAg Level in Group C(Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Normal ALT at EOT in Group C(Week 48)
- Percentage of Participants With HBV DNA <20,000 IU/mL at EOT in Group C(Week 48)
- Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT in Group C(Week 48)
- Percentage of Participants With HBsAg Seroconversion at 24 Weeks After the End of Switch Treatment Period: Switch Group(FU Week 24 (up to 72 weeks overall))
- Change From Baseline in Weight for Age Z-Score in Groups A and B(Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall))
- Change From Baseline in Height for Age Z-Score in Group C(Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall))
- Change From Baseline in Weight for Age Z-Score in Group C(Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall))
- Percentage of Participants With HBeAg Seroconversion at 24 Weeks After EOT in Group C(FU Week 24 (up to 72 weeks overall))
- Change From Baseline in Quantitative Serum ALT Level in Groups A and B(Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall))
- Change From Baseline in Quantitative HBeAg Level in Groups A and B(Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall))
- Change From Baseline in Quantitative HBsAg Level in Groups A and B(Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall))
- Change From Baseline in Quantitative Serum ALT Level in Group C(Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall))
- Change From Baseline in Quantitative HBeAg Level in Group C(Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Loss of HBsAg at 24 Weeks After the End of Switch Treatment Period: Switch Group(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Normal ALT at 24 Weeks After the End of Switch Treatment Period: Switch Group(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) <20,000 International Units Per Milliliter (IU/mL) at 24 Weeks After the End of Switch Treatment Period: Switch Group(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After the End of Switch Treatment Period: Switch Group(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With HBV DNA Undetectable at 24 Weeks After the End of Switch Treatment Period: Switch Group(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After the End of Switch Treatment Period: Switch Group(FU Week 24 (up to 72 weeks overall))
- Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After the End of Switch Treatment Period: Switch Group(FU Week 24 (up to 72 weeks overall))
研究者
研究点 (39)
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