An Open-Label, Multicenter Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Ombitasvir (OBV), Paritaprevir (PTV), Ritonavir (RTV) With or Without Dasabuvir (DSV) and With or Without Ribavirin (RBV) in Pediatric Subjects With Genotype 1 or 4 Chronic Hepatitis C Virus (HCV) Infection (ZIRCON)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 试验地点
- 21
- 主要终点
- Part 1: Maximum Plasma Concentration (Cmax) of Dasabuvir (DSV)
研究概览
简要总结
This was a Phase 2/3, open-label, multicenter study to evaluate the pharmacokinetics (PK), efficacy, and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/RTV) with or without dasabuvir (DSV) and with or without ribavirin (RBV) in Hepatitis C virus (HCV) genotype 1 or 4 (GT1 or GT4)-infected pediatric participants of ≥ 3 to 17 years of age.
详细描述
The study population for Part 1, the PK study, included GT1-infected participants who were noncirrhotic and treatment-naïve (TN). Part 2, the safety and efficacy study, included GT1 or GT4-infected participants who were TN or interferon ([IFN] or Pegylated-interferon alfa-2a or 2b [pegIFN] with or without RBV) treatment-experienced (TE) without cirrhosis or with compensated cirrhosis. In Part 1 and Part 2, the treatment regimen and duration were dependent on HCV GT, GT1 subtype, and cirrhosis status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Positive anti-hepatitis C virus antibody (HCV Ab) and HCV ribonucleic acid (RNA) ≥ 1000 IU/mL at the time of screening
- •HCV genotype 1 for enrollment into Part 1 of the study and genotype 1 or 4 for enrollment into Part 2
- •Parent or legal guardian with the willingness and ability to provide written informed consent and participant willing and able to give assent, as appropriate for age and country
排除标准
- •Female participant who is pregnant, breastfeeding or is considering becoming pregnant
- •Use of known strong inducers and inhibitors (e.g., gemfibrozil) of cytochrome P450 2C8 (CYP2C8) in participants receiving dasabuvir, or strong or moderate inducers of CYP3A, within 2 weeks or 10 half-lives, whichever is longer, of the respective medication/supplement prior to study drug administration.
- •Positive test result for Hepatitis B surface antigen (HbsAg) or anti-human immunodeficiency virus antibody (HIV Ab) test
- •Current enrollment in another interventional clinical study, previous enrollment in this study, prior or current use of any investigational or commercially available anti-HCV agents other than interferons or ribavirin or receipt of any investigational product within 6 weeks prior to study drug administration
研究组 & 干预措施
Adult tablet, 12-17 yr, Part 1
Participants with HCV GT1b without cirrhosis received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75 mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label.
干预措施: Ombitasvir/paritaprevir/ritonavir (Drug)
Adult tablet, 12-17 yr, Part 1
Participants with HCV GT1b without cirrhosis received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75 mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label.
干预措施: Dasabuvir (Drug)
Adult tablet, 12-17 yr, Part 1
Participants with HCV GT1b without cirrhosis received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75 mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label.
干预措施: Ribavirin (Drug)
Adult tablet, 12-17 yr, Part 2
Participants with HCV GT1b received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT1a with compensated cirrhosis received 24-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT4 received 12-week treatment with the OBV/PTV/RTV formulation and ribavirin 200 mg tablets were administered orally per local label.
干预措施: Ombitasvir/paritaprevir/ritonavir (Drug)
Adult tablet, 12-17 yr, Part 2
Participants with HCV GT1b received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT1a with compensated cirrhosis received 24-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT4 received 12-week treatment with the OBV/PTV/RTV formulation and ribavirin 200 mg tablets were administered orally per local label.
干预措施: Dasabuvir (Drug)
Adult tablet, 12-17 yr, Part 2
Participants with HCV GT1b received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT1a with compensated cirrhosis received 24-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT4 received 12-week treatment with the OBV/PTV/RTV formulation and ribavirin 200 mg tablets were administered orally per local label.
干预措施: Ribavirin (Drug)
Mini tablet, 9-11 yr, Part 1
Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.
干预措施: Ombitasvir mini tablet (Drug)
Mini tablet, 9-11 yr, Part 1
Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.
干预措施: Paritaprevir mini tablet (Drug)
Mini tablet, 9-11 yr, Part 1
Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.
干预措施: Ritonavir mini tablet (Drug)
Mini tablet, 9-11 yr, Part 1
Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.
干预措施: Dasabuvir mini tablet (Drug)
Mini tablet, 9-11 yr, Part 1
Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.
干预措施: Ribavirin solution (Drug)
Mini tablet, 3-8 yr, Part 1
Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.
干预措施: Ombitasvir mini tablet (Drug)
Mini tablet, 3-8 yr, Part 1
Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.
干预措施: Paritaprevir mini tablet (Drug)
Mini tablet, 3-8 yr, Part 1
Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.
干预措施: Ritonavir mini tablet (Drug)
Mini tablet, 3-8 yr, Part 1
Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.
干预措施: Dasabuvir mini tablet (Drug)
Mini tablet, 3-8 yr, Part 1
Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.
干预措施: Ribavirin solution (Drug)
结局指标
主要结局
Part 1: Maximum Plasma Concentration (Cmax) of Dasabuvir (DSV)
时间窗: At Week 2
Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Part 1: Maximum Plasma Concentration (Cmax) of Ombitasvir (OBV)
时间窗: At Week 2
Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ombitasvir (OBV)
时间窗: At Week 2
AUC is a measure of how long and how much drug is present in the body after dosing. The amount of ombitasvir present was measured up to 24 hours after dosing.
Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV)
时间窗: At Weeks 2 and 8
Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
Part 1: Maximum Plasma Concentration (Cmax) of Paritaprevir (PTV)
时间窗: At Week 2
Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Paritaprevir (PTV)
时间窗: At Week 2
AUC is a measure of how long and how much drug is present in the body after dosing. The amount of paritaprevir present was measured up to 24 hours after dosing.
Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV)
时间窗: At Weeks 2 and 8
Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
Part 1: Concentration of Drug in Blood Plasma Against Time [Area Under the Curve (AUC)] of Dasabuvir (DSV)
时间窗: At Week 2
AUC is a measure of how long and how much drug is present in the body after dosing. The amount of dasabuvir present was measured up to 12 hours after dosing. For two subjects in the 15-29 kg group, the 24 h concentration was used as the 12 h concentration due to the significant sampling time deviation. For one subject in the 30-44 kg group, the 24 h concentration was used as the 12 h concentration due to the significant sampling time deviation.
Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV)
时间窗: At Weeks 2 and 8
Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
Part 1: Maximum Plasma Concentration (Cmax) of Ritonavir (RTV)
时间窗: At Week 2
Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ritonavir (RTV)
时间窗: At Week 2
AUC is a measure of how long and how much drug is present in the body after dosing. The amount of ritonavir present was measured up to 24 hours after dosing.
Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV)
时间窗: At Weeks 2 and 8
Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12)
时间窗: 12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration)
SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) \< lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
次要结局
- Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12) Summarized by Formulation, Age and Weight Group, and Across All Subjects on the Adult Formulations(12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration))
- Parts 1 & 2: Percentage of Participants With Sustained Virologic Response 24 Weeks After the Last Actual Dose of Study Drug (SVR24), Summarized by Formulation, Age and Weight Group, Across All Subjects, and Across All Subjects on the Adult Formulations(24 weeks after last dose of study drug (Week 36 or 48 depending on treatment duration))
- Parts 1 and 2: Percentage of Participants With Alanine Aminotransferase (ALT) Normalization During Treatment by Formulation, Age and Weight Group, Across All Subjects, and Across All Subjects on the Adult Formulations(12 or 24 weeks after starting study drug, depending on treatment duration)