Open-Label, Multiple-Dose, Dose Escalation Study to Evaluate the Pharmacodynamics, Pharmacokinetics, and Safety of Coadministration of BMS-650032, BMS-790052, and BMS-791325 When Administered for 24 or 12 Weeks in Treatment-Naïve Subjects Infected With Hepatitis C Virus Genotype 1
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 320
- 试验地点
- 28
- 主要终点
- Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12)
研究概览
简要总结
The purpose of this study is to estimate the rate of sustained virologic response (SVR) SVR12, where SVR12 is defined as HCV RNA < LOQ (detectable or undetectable) 12 weeks post-treatment in Genotype 1 & Genotype 4 treatment naive patients, and Genotype (GT1) infected patients who are prior null responders to pegIFN/ribavirin
详细描述
IND numbers: 79,599; 101,943
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
- •Men and women, ages ≥18 years of age
- •Subjects who are naive to HCV treatment, defined as no previous exposure to an Interferon (IFN), Ribavirin (RBV); or any HCV-specific direct acting antiviral or experimental therapy or subjects who are null responders to previous pegylated Interferon alfa (pegIFNα) plus Ribavirin (RBV) treatment
- •Subjects should have chronic hepatitis C (CHC) as documented by:
- •Positive for anti-HCV antibody, HCV RNA, or a positive HCV genotype test at least 6 months prior to screening, and positive for HCV RNA and Anti-HCV antibody at the time of screening, or
- •Positive for anti-HCV antibody and HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed prior to enrollment with evidence of CHC disease, such as the presence of fibrosis)
- •HCV genotype 1a, 1b or 4 only
- •HCV RNA viral load of ≥10,000 IU/mL at screening
- •Have one of the following:
- •Documented Fibrotest score of ≤0.72 and aspartate transferase (transminase) to platelet ratio index (APRI) ≤2; OR
- •Documented liver biopsy within 36 months preceding Day 1 showing absence of cirrhosis OR
- •Documented Fibroscan® ultrasound (where approved) within 12 months of screening showing absence of cirrhosis
- •Body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive
- •Subjects with compensated Child-Pugh A cirrhosis as documented by history of cirrhosis with any prior liver biopsy or Fibroscan® ultrasound (where approved) within 12 months prior to screening
排除标准
- •Evidence of a medical condition associated with chronic liver disease other than HCV (such as but not limited to: hemochromatosis, autoimmune hepatitis,metabolic liver disease, alcoholic liver disease, toxin exposures)
- •History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis
- •Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment
- •Documented or suspected hepatocellular carcinoma (HCC)
- •Positive for hepatitis B surface antigen (HBsAg)
- •Positive for Human Immunodeficiency Virus-1 (HIV-1) and/or Human Immunodeficiency Virus-2 (HIV-2) antibodies
- •Alanine transferase (transminase) (ALT) >5x upper limit of normal (ULN)
- •Total Bilirubin ≥2 mg/dL
研究组 & 干预措施
Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks
BMS-790052 60 mg tablet by mouth once daily for 24 Weeks
BMS 791325 75 mg table by mouth twice daily for 24 Weeks
干预措施: BMS-650032 (Drug)
Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks
BMS-790052 60 mg tablet by mouth once daily for 24 Weeks
BMS 791325 75 mg table by mouth twice daily for 24 Weeks
干预措施: BMS-790052 (Drug)
Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks
BMS-790052 60 mg tablet by mouth once daily for 24 Weeks
BMS 791325 75 mg table by mouth twice daily for 24 Weeks
干预措施: BMS-791325 (Drug)
Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 60 mg tablet by mouth once daily for 12 Weeks
BMS 791325 75 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-650032 (Drug)
Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 60 mg tablet by mouth once daily for 12 Weeks
BMS 791325 75 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-790052 (Drug)
Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 60 mg tablet by mouth once daily for 12 Weeks
BMS 791325 75 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-791325 (Drug)
Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)
* Contingent upon review of safety data from all available treated subjects from Groups 1 and 2
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks
BMS-790052 60 mg tablet by mouth once daily for 24 Weeks
BMS 791325 150 mg table by mouth twice daily for 24 Weeks
干预措施: BMS-650032 (Drug)
Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)
* Contingent upon review of safety data from all available treated subjects from Groups 1 and 2
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks
BMS-790052 60 mg tablet by mouth once daily for 24 Weeks
BMS 791325 150 mg table by mouth twice daily for 24 Weeks
干预措施: BMS-790052 (Drug)
Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)
* Contingent upon review of safety data from all available treated subjects from Groups 1 and 2
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks
BMS-790052 60 mg tablet by mouth once daily for 24 Weeks
BMS 791325 150 mg table by mouth twice daily for 24 Weeks
干预措施: BMS-791325 (Drug)
Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)
* Contingent upon review of safety data from all available treated subjects from Groups 1 and 2
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 60 mg tablet by mouth once daily for 12 Weeks
BMS 791325 150 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-650032 (Drug)
Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)
* Contingent upon review of safety data from all available treated subjects from Groups 1 and 2
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 60 mg tablet by mouth once daily for 12 Weeks
BMS 791325 150 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-790052 (Drug)
Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)
* Contingent upon review of safety data from all available treated subjects from Groups 1 and 2
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 60 mg tablet by mouth once daily for 12 Weeks
BMS 791325 150 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-791325 (Drug)
Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 1 treatment-naive subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 75 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-650032 (Drug)
Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 1 treatment-naive subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 75 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-790052 (Drug)
Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 1 treatment-naive subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 75 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-791325 (Drug)
Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 1 treatment-naive subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 150 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-650032 (Drug)
Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 1 treatment-naive subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 150 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-790052 (Drug)
Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 1 treatment-naive subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 150 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-791325 (Drug)
Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 4 treatment-naive subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 75 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-650032 (Drug)
Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 4 treatment-naive subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 75 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-790052 (Drug)
Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 4 treatment-naive subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 75 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-791325 (Drug)
Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 4 treatment-naive subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 150 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-650032 (Drug)
Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 4 treatment-naive subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 150 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-790052 (Drug)
Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 4 treatment-naive subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 150 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-791325 (Drug)
Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 1 treatment-null/non-responder subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 75 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-650032 (Drug)
Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 1 treatment-null/non-responder subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 75 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-790052 (Drug)
Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 1 treatment-null/non-responder subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 75 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-791325 (Drug)
Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 1 treatment-null/non-responder subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 150 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-650032 (Drug)
Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 1 treatment-null/non-responder subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 150 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-790052 (Drug)
Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 1 treatment-null/non-responder subjects
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks
BMS 791325 150 mg table by mouth twice daily for 12 Weeks
干预措施: BMS-791325 (Drug)
Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 1 treatment-null/non-responder subjects
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 24 Weeks
BMS 791325 75 mg table by mouth twice daily for 24 Weeks
干预措施: BMS-650032 (Drug)
Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 1 treatment-null/non-responder subjects
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 24 Weeks
BMS 791325 75 mg table by mouth twice daily for 24 Weeks
干预措施: BMS-790052 (Drug)
Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 1 treatment-null/non-responder subjects
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 24 Weeks
BMS 791325 75 mg table by mouth twice daily for 24 Weeks
干预措施: BMS-791325 (Drug)
Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 1 treatment-null/non-responder subjects
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 24 Weeks
BMS 791325 150 mg table by mouth twice daily for 24 Weeks
干预措施: BMS-650032 (Drug)
Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 1 treatment-null/non-responder subjects
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 24 Weeks
BMS 791325 150 mg table by mouth twice daily for 24 Weeks
干预措施: BMS-790052 (Drug)
Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 1 treatment-null/non-responder subjects
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks
BMS-790052 30 mg tablet by mouth twice daily for 24 Weeks
BMS 791325 150 mg table by mouth twice daily for 24 Weeks
干预措施: BMS-791325 (Drug)
Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBV
* Genotype 1 treatment-naive subjects
BMS-650032 200 mg tablets orally twice daily 12 weeks
BMS-790052 30 mg tablets orally twice daily 12 weeks
BMS-791325 75 mg tablets orally twice daily 12 weeks
Ribavirin (RBV) tablets orally weight based dosing daily 12 weeks [if subject is < 75 kg: 1000 mg per day orally (2 x 200 mg tablets in AM and 3 x 200 mg tablets in PM), or if ≥ 75 kg: 1200 mg per day orally (3 x 200 mg tablets in AM and 3 x 200 mg tablets in PM]
干预措施: BMS-650032 (Drug)
Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBV
* Genotype 1 treatment-naive subjects
BMS-650032 200 mg tablets orally twice daily 12 weeks
BMS-790052 30 mg tablets orally twice daily 12 weeks
BMS-791325 75 mg tablets orally twice daily 12 weeks
Ribavirin (RBV) tablets orally weight based dosing daily 12 weeks [if subject is < 75 kg: 1000 mg per day orally (2 x 200 mg tablets in AM and 3 x 200 mg tablets in PM), or if ≥ 75 kg: 1200 mg per day orally (3 x 200 mg tablets in AM and 3 x 200 mg tablets in PM]
干预措施: BMS-790052 (Drug)
Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBV
* Genotype 1 treatment-naive subjects
BMS-650032 200 mg tablets orally twice daily 12 weeks
BMS-790052 30 mg tablets orally twice daily 12 weeks
BMS-791325 75 mg tablets orally twice daily 12 weeks
Ribavirin (RBV) tablets orally weight based dosing daily 12 weeks [if subject is < 75 kg: 1000 mg per day orally (2 x 200 mg tablets in AM and 3 x 200 mg tablets in PM), or if ≥ 75 kg: 1200 mg per day orally (3 x 200 mg tablets in AM and 3 x 200 mg tablets in PM]
干预措施: BMS-791325 (Drug)
Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBV
* Genotype 1 treatment-naive subjects
BMS-650032 200 mg tablets orally twice daily 12 weeks
BMS-790052 30 mg tablets orally twice daily 12 weeks
BMS-791325 75 mg tablets orally twice daily 12 weeks
Ribavirin (RBV) tablets orally weight based dosing daily 12 weeks [if subject is < 75 kg: 1000 mg per day orally (2 x 200 mg tablets in AM and 3 x 200 mg tablets in PM), or if ≥ 75 kg: 1200 mg per day orally (3 x 200 mg tablets in AM and 3 x 200 mg tablets in PM]
干预措施: Ribavirin (Drug)
结局指标
主要结局
Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12)
时间窗: 12 weeks post-treatment
次要结局
- Proportion of subjects with HCV ribonucleic acid (RNA) < limit of quantification (LOQ) (detectable and undetectable)(Weeks 1, 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22 and 24 weeks of therapy; at end of treatment (EOT) (following 12 or 24 weeks of treatment, by Group); and Weeks 4, 12, 24, 36, and 48 weeks post-treatment)
- Proportion of subjects with HCV ribonucleic acid (RNA) undetectable(Weeks 1, 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22 and 24 weeks of therapy; at end of treatment (EOT) (following 12 or 24 weeks of treatment, by Group); and Weeks 4, 12, 24, 36, and 48 weeks post-treatment)
- Proportion of subjects who experience viral breakthrough(Formal analysis at SVR12, Week 48 of follow up period (or upon occurrence))
- Proportion of subjects who experience viral relapse defined as confirmed quantifiable HCV RNA ≥ 25 IU/mL (>LOQ) in a subject with HCV RNA < LOQ or undetectable at End of treatment (EOT)(End of treatment (Maximum up to 24 Weeks))
- Maximum observed plasma concentration (Cmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712(Day 1 and Day 14)
- Observed plasma concentration at 12 hours (C12) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712(Day 1 and Day 14)
- Observed plasma concentration at 24 hours (C24) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712(Day 1 and Day 14)
- Trough observed plasma concentration (Ctrough) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712(Day 1 and Day 14)
- Time of maximum observed plasma concentration (Tmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712(Day 1 and Day 14)
- Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-650032, BMS-790052, BMS 791325, and BMS-794712(Day 1 and Day 14)
- HCV genomic substitutions associated with exposure of BMS-650032, BMS-790052, and BMS-791325(At the time of viral breakthrough or relapse)
- Frequency of deaths, serious adverse events (SAEs), discontinuations due to adverse events (AEs), severity Grade 3/4 AEs, and severity Grade 3/4 laboratory abnormalities(Formal analysis at week 48 of follow up period (or upon occurrence))