Chronic Hepatitis C Infection
Conditions
Keywords
Hepatitis C Virus, Hepatitis C Genotype 1, Hepatitis C Genotype 4, Pediatric
Brief summary
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.
Detailed description
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.
Interventions
DRUGRibavirin solution
Oral solution
DRUGDasabuvir mini tablet
Film-coated tablet for oral use
Film-coated tablet for oral use
DRUGDasabuvir
Film-coated tablet for oral use
DRUGRibavirin
Film-coated tablet for oral use
DRUGOmbitasvir mini tablet
Film-coated tablet for oral use
DRUGParitaprevir mini tablet
Film-coated tablet for oral use
DRUGRitonavir mini tablet
Film-coated tablet for oral use
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Positive anti-hepatitis C virus antibody (HCV Ab) and HCV ribonucleic acid (RNA) ≥ 1000 IU/mL at the time of screening 2. HCV genotype 1 for enrollment into Part 1 of the study and genotype 1 or 4 for enrollment into Part 2 3. 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
Exclusion criteria
1. Female participant who is pregnant, breastfeeding or is considering becoming pregnant 2. 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. 3. Positive test result for Hepatitis B surface antigen (HbsAg) or anti-human immunodeficiency virus antibody (HIV Ab) test 4. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12) | 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. |
| Part 1: Maximum Plasma Concentration (Cmax) of Ritonavir (RTV) | 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) | 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) | 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 Ombitasvir (OBV) | 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) | 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) | 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) | 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) | 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) | 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 Dasabuvir (DSV) | 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 Against Time [Area Under the Curve (AUC)] of Dasabuvir (DSV) | 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) | At Weeks 2 and 8 | Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | SVR24 is defined as hepatitis C virus ribonucleic acid (HCV RNA) \< lower limit of quantification (LLOQ) 24 weeks after the last actual dose of study drug. |
| 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 | Alanine aminotransferase (ALT) normalization during treatment is defined as ALT ≤ the upper limit of normal (ULN) at the final treatment visit for participants with ALT \> ULN at baseline. |
| 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) | 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. |
Countries
Belgium, Germany, Puerto Rico, Spain, United States
Participant flow
Pre-assignment details
Safety population: all participants who received at least one dose of study drug in Part 1 or Part 2
Participants by arm
| Arm | Count |
|---|---|
| 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. | 12 |
| 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. | 26 |
| 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. | 12 |
| 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. | 14 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 3 | 1 | 3 |
| Overall Study | Other, not specified | 0 | 0 | 1 | 0 |
| Overall Study | Withdrew consent | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Adult Tablet, 12-17 yr, Part 1 | Adult Tablet, 12-17 yr, Part 2 | Mini Tablet, 9-11 yr, Part 1 | Mini Tablet, 3-8 yr, Part 1 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 15.4 years STANDARD_DEVIATION 1.73 | 15.0 years STANDARD_DEVIATION 1.68 | 9.8 years STANDARD_DEVIATION 0.83 | 4.8 years STANDARD_DEVIATION 1.67 | 11.9 years STANDARD_DEVIATION 4.54 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 3 Participants | 0 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Multi race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 23 Participants | 10 Participants | 10 Participants | 49 Participants |
| Sex: Female, Male Female | 9 Participants | 16 Participants | 6 Participants | 11 Participants | 42 Participants |
| Sex: Female, Male Male | 3 Participants | 10 Participants | 6 Participants | 3 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 26 | 0 / 38 | 0 / 12 | 0 / 14 | 0 / 26 | 0 / 64 |
| other Total, other adverse events | 11 / 12 | 17 / 26 | 28 / 38 | 12 / 12 | 9 / 14 | 21 / 26 | 49 / 64 |
| serious Total, serious adverse events | 0 / 12 | 0 / 26 | 0 / 38 | 1 / 12 | 0 / 14 | 1 / 26 | 1 / 64 |
Outcome results
Primary
Part 1: Concentration of Drug in Blood Plasma Against Time [Area Under the Curve (AUC)] of Dasabuvir (DSV)
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.
Time frame: At Week 2
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 - 29 kg Body Weight | Part 1: Concentration of Drug in Blood Plasma Against Time [Area Under the Curve (AUC)] of Dasabuvir (DSV) | 3960 ng•h/mL | Geometric Coefficient of Variation 44 |
| 30 - 44 kg Body Weight | Part 1: Concentration of Drug in Blood Plasma Against Time [Area Under the Curve (AUC)] of Dasabuvir (DSV) | 5960 ng•h/mL | Geometric Coefficient of Variation 47 |
| ≥ 45 kg Body Weight | Part 1: Concentration of Drug in Blood Plasma Against Time [Area Under the Curve (AUC)] of Dasabuvir (DSV) | 4630 ng•h/mL | Geometric Coefficient of Variation 49 |
Primary
Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ombitasvir (OBV)
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.
Time frame: At Week 2
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 - 29 kg Body Weight | Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ombitasvir (OBV) | 1270 ng•h/mL | Geometric Coefficient of Variation 26 |
| 30 - 44 kg Body Weight | Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ombitasvir (OBV) | 1490 ng•h/mL | Geometric Coefficient of Variation 12 |
| ≥ 45 kg Body Weight | Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ombitasvir (OBV) | 1060 ng•h/mL | Geometric Coefficient of Variation 43 |
Primary
Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Paritaprevir (PTV)
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.
Time frame: At Week 2
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 - 29 kg Body Weight | Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Paritaprevir (PTV) | 2180 ng•h/mL | Geometric Coefficient of Variation 136 |
| 30 - 44 kg Body Weight | Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Paritaprevir (PTV) | 8640 ng•h/mL | Geometric Coefficient of Variation 90 |
| ≥ 45 kg Body Weight | Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Paritaprevir (PTV) | 5770 ng•h/mL | Geometric Coefficient of Variation 152 |
Primary
Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ritonavir (RTV)
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.
Time frame: At Week 2
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 - 29 kg Body Weight | Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ritonavir (RTV) | 6570 ng•h/mL | Geometric Coefficient of Variation 60 |
| 30 - 44 kg Body Weight | Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ritonavir (RTV) | 14100 ng•h/mL | Geometric Coefficient of Variation 49 |
| ≥ 45 kg Body Weight | Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ritonavir (RTV) | 8900 ng•h/mL | Geometric Coefficient of Variation 37 |
Primary
Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV)
Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
Time frame: At Weeks 2 and 8
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 15 - 29 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV) | Week 2 | 110 ng/mL | Geometric Coefficient of Variation 57 |
| 15 - 29 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV) | Week 8 | 168 ng/mL | Geometric Coefficient of Variation 82 |
| 30 - 44 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV) | Week 2 | 215 ng/mL | Geometric Coefficient of Variation 54 |
| 30 - 44 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV) | Week 8 | 264 ng/mL | Geometric Coefficient of Variation 65 |
| ≥ 45 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV) | Week 2 | 165 ng/mL | Geometric Coefficient of Variation 56 |
| ≥ 45 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV) | Week 8 | 191 ng/mL | Geometric Coefficient of Variation 60 |
Primary
Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV)
Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
Time frame: At Weeks 2 and 8
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 15 - 29 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV) | Week 2 | 24.7 ng/mL | Geometric Coefficient of Variation 32 |
| 15 - 29 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV) | Week 8 | 29.6 ng/mL | Geometric Coefficient of Variation 78 |
| 30 - 44 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV) | Week 8 | 30.4 ng/mL | Geometric Coefficient of Variation 24 |
| 30 - 44 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV) | Week 2 | 28.2 ng/mL | Geometric Coefficient of Variation 16 |
| ≥ 45 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV) | Week 8 | 20.9 ng/mL | Geometric Coefficient of Variation 58 |
| ≥ 45 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV) | Week 2 | 21.8 ng/mL | Geometric Coefficient of Variation 39 |
Primary
Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV)
Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
Time frame: At Weeks 2 and 8
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 15 - 29 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV) | Week 2 | 9.86 ng/mL | Geometric Coefficient of Variation 113 |
| 15 - 29 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV) | Week 8 | 17.3 ng/mL | Geometric Coefficient of Variation 136 |
| 30 - 44 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV) | Week 2 | 16.1 ng/mL | Geometric Coefficient of Variation 112 |
| 30 - 44 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV) | Week 8 | 18.4 ng/mL | Geometric Coefficient of Variation 89 |
| ≥ 45 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV) | Week 2 | 18.0 ng/mL | Geometric Coefficient of Variation 78 |
| ≥ 45 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV) | Week 8 | 23.5 ng/mL | Geometric Coefficient of Variation 86 |
Primary
Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV)
Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
Time frame: At Weeks 2 and 8
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 15 - 29 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV) | Week 8 | 91.8 ng/mL | Geometric Coefficient of Variation 268 |
| 15 - 29 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV) | Week 2 | 16.1 ng/mL | Geometric Coefficient of Variation 72 |
| 30 - 44 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV) | Week 8 | 38.1 ng/mL | Geometric Coefficient of Variation 112 |
| 30 - 44 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV) | Week 2 | 32.1 ng/mL | Geometric Coefficient of Variation 63 |
| ≥ 45 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV) | Week 8 | 58.2 ng/mL | Geometric Coefficient of Variation 138 |
| ≥ 45 kg Body Weight | Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV) | Week 2 | 29.8 ng/mL | Geometric Coefficient of Variation 54 |
Primary
Part 1: Maximum Plasma Concentration (Cmax) of Dasabuvir (DSV)
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.
Time frame: At Week 2
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 - 29 kg Body Weight | Part 1: Maximum Plasma Concentration (Cmax) of Dasabuvir (DSV) | 579 ng/mL | Geometric Coefficient of Variation 44 |
| 30 - 44 kg Body Weight | Part 1: Maximum Plasma Concentration (Cmax) of Dasabuvir (DSV) | 830 ng/mL | Geometric Coefficient of Variation 45 |
| ≥ 45 kg Body Weight | Part 1: Maximum Plasma Concentration (Cmax) of Dasabuvir (DSV) | 671 ng/mL | Geometric Coefficient of Variation 48 |
Primary
Part 1: Maximum Plasma Concentration (Cmax) of Ombitasvir (OBV)
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.
Time frame: At Week 2
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 - 29 kg Body Weight | Part 1: Maximum Plasma Concentration (Cmax) of Ombitasvir (OBV) | 99.6 ng/mL | Geometric Coefficient of Variation 27 |
| 30 - 44 kg Body Weight | Part 1: Maximum Plasma Concentration (Cmax) of Ombitasvir (OBV) | 116 ng/mL | Geometric Coefficient of Variation 14 |
| ≥ 45 kg Body Weight | Part 1: Maximum Plasma Concentration (Cmax) of Ombitasvir (OBV) | 83.7 ng/mL | Geometric Coefficient of Variation 39 |
Primary
Part 1: Maximum Plasma Concentration (Cmax) of Paritaprevir (PTV)
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.
Time frame: At Week 2
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 - 29 kg Body Weight | Part 1: Maximum Plasma Concentration (Cmax) of Paritaprevir (PTV) | 294 ng/mL | Geometric Coefficient of Variation 152 |
| 30 - 44 kg Body Weight | Part 1: Maximum Plasma Concentration (Cmax) of Paritaprevir (PTV) | 1540 ng/mL | Geometric Coefficient of Variation 71 |
| ≥ 45 kg Body Weight | Part 1: Maximum Plasma Concentration (Cmax) of Paritaprevir (PTV) | 870 ng/mL | Geometric Coefficient of Variation 125 |
Primary
Part 1: Maximum Plasma Concentration (Cmax) of Ritonavir (RTV)
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.
Time frame: At Week 2
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 - 29 kg Body Weight | Part 1: Maximum Plasma Concentration (Cmax) of Ritonavir (RTV) | 1090 ng/mL | Geometric Coefficient of Variation 67 |
| 30 - 44 kg Body Weight | Part 1: Maximum Plasma Concentration (Cmax) of Ritonavir (RTV) | 1830 ng/mL | Geometric Coefficient of Variation 42 |
| ≥ 45 kg Body Weight | Part 1: Maximum Plasma Concentration (Cmax) of Ritonavir (RTV) | 1180 ng/mL | Geometric Coefficient of Variation 35 |
Primary
Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12)
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.
Time frame: 12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration)
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 or 2; those with missing data after backwards imputation were treated as nonresponders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 - 29 kg Body Weight | Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12) | 98.4 percentage of participants |
Comparison: According to the Highlights of Prescribing Information of PEGASYS, the SVR24 rate was 47% among 45 treatment-naïve pediatric participants with HCV GT1 in the NV17424 trial. To show that the DAA regimen is superior to this current standard of care by 20%, the lower bound of the 2-sided 95% confidence interval of the SVR12 rate across all participants in the study must be greater than 67%.95% CI: [91.7, 99.7]
Secondary
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
SVR24 is defined as hepatitis C virus ribonucleic acid (HCV RNA) \< lower limit of quantification (LLOQ) 24 weeks after the last actual dose of study drug.
Time frame: 24 weeks after last dose of study drug (Week 36 or 48 depending on treatment duration)
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 or 2; those with missing data after backwards imputation were treated as nonresponders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 - 29 kg Body Weight | 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 | 96.9 percentage of participants |
| 30 - 44 kg Body Weight | 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 | 100 percentage of participants |
| ≥ 45 kg Body Weight | 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 | 100.0 percentage of participants |
| Mini-tablet, 9-11 YR, ≥ 45 kg | 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 | 88.9 percentage of participants |
| Mini-tablet, 3-8 YR, 15 to 29 kg | 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 | 100.0 percentage of participants |
| Mini-tablet Total | 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 | 92.9 percentage of participants |
| Mini-tablet Total | 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 | 92.3 percentage of participants |
Secondary
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
Alanine aminotransferase (ALT) normalization during treatment is defined as ALT ≤ the upper limit of normal (ULN) at the final treatment visit for participants with ALT \> ULN at baseline.
Time frame: 12 or 24 weeks after starting study drug, depending on treatment duration
Population: Intention-to-treat population including participants whose alanine aminotransferase (ALT) levels were \> the upper limit of normal at baseline and who had available on-treatment ALT data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 - 29 kg Body Weight | 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 | 87.5 percentage of participants |
| 30 - 44 kg Body Weight | 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 | 100 percentage of participants |
| ≥ 45 kg Body Weight | 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 | 100 percentage of participants |
| Mini-tablet, 9-11 YR, ≥ 45 kg | 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 | 80.0 percentage of participants |
| Mini-tablet, 3-8 YR, 15 to 29 kg | 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 | 87.5 percentage of participants |
| Mini-tablet Total | 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 | 87.5 percentage of participants |
Secondary
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
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.
Time frame: 12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration)
Population: Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 or 2; those with missing data after backwards imputation were treated as nonresponders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 - 29 kg Body Weight | 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 | 100 percentage of participants |
| 30 - 44 kg Body Weight | 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 | 100 percentage of participants |
| ≥ 45 kg Body Weight | 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 | 100 percentage of participants |
| Mini-tablet, 9-11 YR, ≥ 45 kg | 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 | 100 percentage of participants |
| Mini-tablet, 3-8 YR, 15 to 29 kg | 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 | 92.9 percentage of participants |
| Mini-tablet Total | 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 | 96.2 percentage of participants |