Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis C (FOURward Study)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 35
- 试验地点
- 7
- 主要终点
- Percentage of Participants With Sustained Virologic Response 12 (SVR12)
研究概览
简要总结
The purpose of the study is to determine whether the combination of Daclatasvir (DCV), Asunaprevir (ASV), BMS-791325 and Sofosbuvir is effective and safe in treating Hepatitis-C virus.
详细描述
Allocation:
Initial Therapy: Randomized Controlled Trial: Participants are assigned to intervention groups by chance
Rescue Therapy: Nonrandomized Trial: Participants are expressly assigned to intervention groups through a non-random method such as physician choice
Number of Arms:
Initial Therapy: 2 Groups
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and Females ≥18 years of age, inclusive
- •Chronic HCV infection Genotype 1 only
- •Non-cirrhotic
- •Treatment naive subjects with no previous exposure to an Interferon formulation (ie, IFNα, pegIFNα), ribavirin (RBV) or HCV Direct Acting Antiviral (DAA) (protease, polymerase inhibitor, etc.)
排除标准
- •HCV Genotype other than Genotype 1
- •Documented or suspected hepatocellular carcinoma
- •Evidence of decompensated liver disease
- •Contraindication(s) to Peg/RBV therapy
研究组 & 干预措施
Arm 1: DCV/ASV/BMS-791325+Sofosbuvir
Initial Therapy:
Daclatasvir/Asunaprevir/BMS-791325 [30 mg (as the free base)/200 mg/75 mg (as the free base)] film coated Fixed Dose Combination tablet twice daily orally for 4 weeks
Sofosbuvir 400 mg tablet once daily orally for 4 weeks
干预措施: DCV/ASV/BMS-791325 (Drug)
Arm 1: DCV/ASV/BMS-791325+Sofosbuvir
Initial Therapy:
Daclatasvir/Asunaprevir/BMS-791325 [30 mg (as the free base)/200 mg/75 mg (as the free base)] film coated Fixed Dose Combination tablet twice daily orally for 4 weeks
Sofosbuvir 400 mg tablet once daily orally for 4 weeks
干预措施: Sofosbuvir (Drug)
Arm 2: DCV/ASV/BMS-791325 + Sofosbuvir
Initial Therapy
Daclatasvir/Asunaprevir/BMS-791325 [30 mg (as the free base)/200 mg/75 mg (as the free base)] film coated Fixed Dose Combination tablet twice daily orally for 6 weeks
Sofosbuvir 400 mg tablet once daily orally for 6 weeks
干预措施: DCV/ASV/BMS-791325 (Drug)
Arm 2: DCV/ASV/BMS-791325 + Sofosbuvir
Initial Therapy
Daclatasvir/Asunaprevir/BMS-791325 [30 mg (as the free base)/200 mg/75 mg (as the free base)] film coated Fixed Dose Combination tablet twice daily orally for 6 weeks
Sofosbuvir 400 mg tablet once daily orally for 6 weeks
干预措施: Sofosbuvir (Drug)
Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-2a
Daclatasvir/Asunaprevir/BMS-791325 [30 mg (as the free base)/200 mg/75 mg (as the free base)] film coated Fixed Dose Combination tablet twice daily orally for 12 weeks
Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks
With or without Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks
干预措施: DCV/ASV/BMS-791325 (Drug)
Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-2a
Daclatasvir/Asunaprevir/BMS-791325 [30 mg (as the free base)/200 mg/75 mg (as the free base)] film coated Fixed Dose Combination tablet twice daily orally for 12 weeks
Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks
With or without Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks
干预措施: Ribavirin (Drug)
Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-2a
Daclatasvir/Asunaprevir/BMS-791325 [30 mg (as the free base)/200 mg/75 mg (as the free base)] film coated Fixed Dose Combination tablet twice daily orally for 12 weeks
Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks
With or without Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks
干预措施: Peginterferon α-2a (Drug)
Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a
Sofosbuvir 400 mg tablet once daily orally for 12 weeks
Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks
Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks
干预措施: Ribavirin (Drug)
Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a
Sofosbuvir 400 mg tablet once daily orally for 12 weeks
Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks
Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks
干预措施: Sofosbuvir (Drug)
Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a
Sofosbuvir 400 mg tablet once daily orally for 12 weeks
Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks
Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks
干预措施: Peginterferon α-2a (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Virologic Response 12 (SVR12)
时间窗: 12 Weeks after treatment discontinuation (Follow-up Week 12)
SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) \< lower limit of quantitation (LLOQ) target detected (TD) or not detected (TND) at post-treatment follow-up Week 12. Imputed SVR12 was based on Next Value Carried Backwards approach.
Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment
时间窗: From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)
SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect.
Number of Participants With Selected Grade 3/4 Laboratory Abnormalities
时间窗: From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)
Grade 3/4 laboratory abnormalities (hematology, electrolyte, lipase, liver function, metabolic, renal function, urinalysis). The Week 24 data set was used to evaluate the Week-24 on-treatment safety. The cumulative data set was used to evaluate the safety while on treatment. Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death.
次要结局
- Percentage of Participants With End of Treatment Response (EOTR)(End of the treatment)
- Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND(Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24))
- Percentage of Participants Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b(Post-treatment Week 12)
- Percentage of Participants Who Achieved HCV RNA < LLOQ TND(Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2, 4, 12 and 24)
- Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype)(Post-treatment Week 12)