A Phase 3 Evaluation of Daclatasvir in Combination With Peginterferon Lambda-1a and Ribavirin (RBV) or Telaprevir in Combination With Peginterferon Alfa-2a and RBV in Patients With Chronic Hepatitis C Genotype 1b Who Are Treatment naïve or Prior Relapsers to Alfa/RBV Therapy (the STRUCTURE Study)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 444
- 试验地点
- 9
- 主要终点
- Proportion of subjects with Sustained Virologic Response at post-treatment follow-up Week 12 (SVR12)
研究概览
简要总结
The purpose of this study is to determine if treatment with Pegylated Interferon Lambda-1a, given in combination with Ribavirin and Daclatasvir for 24 weeks, is as safe and effective as the standard treatment with Pegylated Interferon Alfa-2a + Ribavirin + Telaprevir in subjects who are infected with Chronic Hepatitis C virus genotype 1b and have never received any prior anti-HCV treatment, or who have relapsed after an initial, successful treatment with Pegylated Interferon Alfa + Ribavirin
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
- •Patients chronically infected with HCV Genotype-1b
- •Naïve to prior treatment or documented evidence of relapse after completion of the prescribed duration of treatment (duration may be 24 or 48 weeks, to be determined based upon local guidelines)
- •HCV RNA viral load ≥100,000 IU/mL at screening
- •Patients with compensated cirrhosis are permitted
排除标准
- •Infection with Hepatitis C virus (HCV) other than Genotype-1b
- •Positive Hepatitis B surface antigen (HBsAg) or Human immunodeficiency virus (HIV)-1/HIV-2 antibody test at screening
- •Evidence of chronic liver disease caused by diseases other than chronic HCV infection
- •Current evidence of or history of variceal bleeding, hepatic encephalopathy, or ascites requiring diuretics or paracentesis or evidence of any of these findings on physical examination performed at screening
- •Current or known history of cancer (except adequately treated in situ carcinoma of the cervix, or basal or squamous cell carcinoma of the skin) within 5 years prior to screening
- •Current evidence or known history of decompensated cirrhosis based on radiologic criteria or biopsy results and clinical criteria
- •Laboratory values:
- •Hemoglobin <12.0 g/dL (males) or <11.0 g/dL (females)
- •Platelets <90,000/mm3
- •Total serum bilirubin ≥2 mg/dL (unless due to Gilbert's disease)
研究组 & 干预措施
Peginterferon Lambda-1a + Ribavirin + Daclatasvir
Peginterferon Lambda-1a 180 µg solution for subcutaneous injection, once a week for 24 Weeks
Ribavirin 200 mg tablets [1000-1200 mg total daily dose: subjects should take either 400 mg (2 tablets for subjects < 75 kg) or 600 mg (3 tablets for subjects ≥ 75 kg) in the morning with food and 600 mg (3 tablets) in the evening with food] by mouth, twice daily, for 24 weeks
Daclatasvir 60 mg tablets by mouth, once a day for 12 weeks
干预措施: Peginterferon Lambda-1a (Biological)
Peginterferon Lambda-1a + Ribavirin + Daclatasvir
Peginterferon Lambda-1a 180 µg solution for subcutaneous injection, once a week for 24 Weeks
Ribavirin 200 mg tablets [1000-1200 mg total daily dose: subjects should take either 400 mg (2 tablets for subjects < 75 kg) or 600 mg (3 tablets for subjects ≥ 75 kg) in the morning with food and 600 mg (3 tablets) in the evening with food] by mouth, twice daily, for 24 weeks
Daclatasvir 60 mg tablets by mouth, once a day for 12 weeks
干预措施: Ribavirin (Drug)
Peginterferon Lambda-1a + Ribavirin + Daclatasvir
Peginterferon Lambda-1a 180 µg solution for subcutaneous injection, once a week for 24 Weeks
Ribavirin 200 mg tablets [1000-1200 mg total daily dose: subjects should take either 400 mg (2 tablets for subjects < 75 kg) or 600 mg (3 tablets for subjects ≥ 75 kg) in the morning with food and 600 mg (3 tablets) in the evening with food] by mouth, twice daily, for 24 weeks
Daclatasvir 60 mg tablets by mouth, once a day for 12 weeks
干预措施: Daclatasvir (Drug)
Peginterferon Alfa-2a + Ribavirin + Telaprevir
Peginterferon Alfa-2a 180 µg solution for subcutaneous injection, once a week for 24 to 48 weeks depending on response
Ribavirin 200 mg tablets [1000-1200 mg total daily dose: subjects should take either 400 mg (2 tablets for subjects < 75 kg) or 600 mg (3 tablets for subjects ≥ 75 kg) in the morning with food and 600 mg (3 tablets) in the evening with food] by mouth, twice daily, for 24 to 48 weeks depending on response
Telaprevir 375 mg tablets [2250 mg total daily dose: subjects should take 750 mg (two 375 mg tablets) orally three times a day, approximately 7-9 hours apart) for 12 weeks
干预措施: Peginterferon Alfa-2a (Biological)
Peginterferon Alfa-2a + Ribavirin + Telaprevir
Peginterferon Alfa-2a 180 µg solution for subcutaneous injection, once a week for 24 to 48 weeks depending on response
Ribavirin 200 mg tablets [1000-1200 mg total daily dose: subjects should take either 400 mg (2 tablets for subjects < 75 kg) or 600 mg (3 tablets for subjects ≥ 75 kg) in the morning with food and 600 mg (3 tablets) in the evening with food] by mouth, twice daily, for 24 to 48 weeks depending on response
Telaprevir 375 mg tablets [2250 mg total daily dose: subjects should take 750 mg (two 375 mg tablets) orally three times a day, approximately 7-9 hours apart) for 12 weeks
干预措施: Ribavirin (Drug)
Peginterferon Alfa-2a + Ribavirin + Telaprevir
Peginterferon Alfa-2a 180 µg solution for subcutaneous injection, once a week for 24 to 48 weeks depending on response
Ribavirin 200 mg tablets [1000-1200 mg total daily dose: subjects should take either 400 mg (2 tablets for subjects < 75 kg) or 600 mg (3 tablets for subjects ≥ 75 kg) in the morning with food and 600 mg (3 tablets) in the evening with food] by mouth, twice daily, for 24 to 48 weeks depending on response
Telaprevir 375 mg tablets [2250 mg total daily dose: subjects should take 750 mg (two 375 mg tablets) orally three times a day, approximately 7-9 hours apart) for 12 weeks
干预措施: Telaprevir (Drug)
结局指标
主要结局
Proportion of subjects with Sustained Virologic Response at post-treatment follow-up Week 12 (SVR12)
时间窗: Post treatment follow-up Week 12
次要结局
- Proportion of subjects who achieve SVR12 in treatment-naive subjects(Post treatment follow-up Week 12)
- Proportion of subjects with rash related dermatologic events(Up to 12 weeks of treatment)
- Proportion of subjects with on-treatment interferon (IFN) associated flu like/musculoskeletal symptoms(Up to 48 Weeks)
- Proportion of subjects who achieve SVR24 [Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Lower limit of quantitation (LLOQ)] at post-treatment follow-up Week 24(Post treatment follow-up Week 24)
- Proportion of subjects with treatment emergent laboratory abnormalities by toxicity grade through End of treatment (EOT)(Maximum of 72 weeks)
- Proportion of subjects who achieve SVR12 with a 24-week treatment regimen(Post treatment follow-up Week 12)
- Proportion of subjects with the following on-treatment interferon-associated neuropsychiatric symptoms through EOT(Maximum of 48 weeks)
- Proportion of subjects who develop treatment emergent cytopenic abnormalities(Up to 48 Weeks)
- Proportion of subjects with adverse events (AEs), Serious adverse events (SAEs), dose reductions, and discontinuations due to AEs through end of follow-up(Maximum of 72 weeks)
- Proportion of subjects who achieve Extended rapid virologic response (eRVR) (HCV RNA < LLOQ target not detected at Weeks 4 and 12 of treatment)(Weeks 4 and 12 of treatment)
- Patient Health Questionnaire-9 (PHQ-9) score through end of follow-up(Maximum of 72 weeks)
- Association of Single nucleotide polymorphism (SNPs) in Interleukin 28B (IL28B) (including rs12979860) or equilibrative nucleoside transporter 1 (ENT1) with clinical responses(Post-treatment follow-up Week 12)
- Resistant variants associated with virologic failure through end of follow-up(Maximum of 72 weeks)