A Study to Evaluate Treatment of Hepatitis C Virus Infection in Pediatric Subjects

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.

• Ombitasvir/paritaprevir/ritonavir (Drug), also known as Ombitasvir also known as ABT-267, Paritaprevir also known as ABT-450, Ombitsvir/paritaprevir/ritonavir also known as Viekirax: Film-coated tablet for oral use
• Dasabuvir (Drug), also known as Exviera, ABT-333: Film-coated tablet for oral use
• Ribavirin (Drug): Film-coated tablet for oral use
• Ombitasvir mini tablet (Drug), also known as ABT-267: Film-coated tablet for oral use
• Paritaprevir mini tablet (Drug), also known as ABT-450: Film-coated tablet for oral use
• Ritonavir mini tablet (Drug): Film-coated tablet for oral use
• Dasabuvir mini tablet (Drug), also known as Exviera, ABT-333: Film-coated tablet for oral use
• Ribavirin solution (Drug): Oral solution

Primary outcomes

• 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.
• 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.
• 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.

Secondary outcomes

• 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.
• 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.

Sex: All, ages: 3 Years to 17 Years

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

Participant flow

Outcome results

• Part 1: Maximum Plasma Concentration (Cmax) of Ombitasvir (OBV) (Primary), Geometric mean, ng/mL: 15 - 29 kg Body Weight 99.6 +/- 27; 30 - 44 kg Body Weight 116 +/- 14; ≥ 45 kg Body Weight 83.7 +/- 39
• Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ombitasvir (OBV) (Primary), Geometric mean, ng•h/mL: 15 - 29 kg Body Weight 1270 +/- 26; 30 - 44 kg Body Weight 1490 +/- 12; ≥ 45 kg Body Weight 1060 +/- 43
• Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV) (Primary), Geometric mean, ng/mL: 15 - 29 kg Body Weight 24.7 +/- 32; 30 - 44 kg Body Weight 28.2 +/- 16; ≥ 45 kg Body Weight 21.8 +/- 39
• Part 1: Maximum Plasma Concentration (Cmax) of Paritaprevir (PTV) (Primary), Geometric mean, ng/mL: 15 - 29 kg Body Weight 294 +/- 152; 30 - 44 kg Body Weight 1540 +/- 71; ≥ 45 kg Body Weight 870 +/- 125
• Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Paritaprevir (PTV) (Primary), Geometric mean, ng•h/mL: 15 - 29 kg Body Weight 2180 +/- 136; 30 - 44 kg Body Weight 8640 +/- 90; ≥ 45 kg Body Weight 5770 +/- 152
• Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV) (Primary), Geometric mean, ng/mL: 15 - 29 kg Body Weight 9.86 +/- 113; 30 - 44 kg Body Weight 16.1 +/- 112; ≥ 45 kg Body Weight 18.0 +/- 78
• Part 1: Maximum Plasma Concentration (Cmax) of Dasabuvir (DSV) (Primary), Geometric mean, ng/mL: 15 - 29 kg Body Weight 579 +/- 44; 30 - 44 kg Body Weight 830 +/- 45; ≥ 45 kg Body Weight 671 +/- 48
• Part 1: Concentration of Drug in Blood Plasma Against Time [Area Under the Curve (AUC)] of Dasabuvir (DSV) (Primary), Geometric mean, ng•h/mL: 15 - 29 kg Body Weight 3960 +/- 44; 30 - 44 kg Body Weight 5960 +/- 47; ≥ 45 kg Body Weight 4630 +/- 49
• Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV) (Primary), Geometric mean, ng/mL: 15 - 29 kg Body Weight 110 +/- 57; 30 - 44 kg Body Weight 215 +/- 54; ≥ 45 kg Body Weight 165 +/- 56
• Part 1: Maximum Plasma Concentration (Cmax) of Ritonavir (RTV) (Primary), Geometric mean, ng/mL: 15 - 29 kg Body Weight 1090 +/- 67; 30 - 44 kg Body Weight 1830 +/- 42; ≥ 45 kg Body Weight 1180 +/- 35
• Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ritonavir (RTV) (Primary), Geometric mean, ng•h/mL: 15 - 29 kg Body Weight 6570 +/- 60; 30 - 44 kg Body Weight 14100 +/- 49; ≥ 45 kg Body Weight 8900 +/- 37
• Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV) (Primary), Geometric mean, ng/mL: 15 - 29 kg Body Weight 16.1 +/- 72; 30 - 44 kg Body Weight 32.1 +/- 63; ≥ 45 kg Body Weight 29.8 +/- 54
• Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12) (Primary), Number, percentage of participants: All Participants, Total 98.4 (91.7 to 99.7)
• 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 (Secondary), Number, percentage of participants: Adult Tablet, 12-17 YR, ≥ 45 kg 100 (90.8 to 100.0); Mini-tablet, 9-11 YR, 15 to 29 kg 100 (20.7 to 100.0); Mini-tablet, 9-11 YR, 30 to 44 kg 100 (70.1 to 100.0); Mini-tablet, 9-11 YR, ≥ 45 kg 100 (34.2 to 100.0); Mini-tablet, 3-8 YR, 15 to 29 kg 92.9 (68.5 to 98.7); Mini-tablet Total 96.2 (81.1 to 99.3)
• 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 (Secondary), Number, percentage of participants: Participants in Parts 1 and 2 of the Study 96.9 (89.3 to 99.1); Adult Tablet, 12-17 YR, ≥ 45 kg 100 (90.8 to 100.0); Mini-tablet, 9-11 YR, 15 to 29 kg 100.0 (20.7 to 100.0); Mini-tablet, 9-11 YR, 30 to 44 kg 88.9 (56.5 to 98.0); Mini-tablet, 9-11 YR, ≥ 45 kg 100.0 (34.2 to 100.0); Mini-tablet, 3-8 YR, 15 to 29 kg 92.9 (68.5 to 98.7); Mini-tablet Total 92.3 (75.9 to 97.9)
• 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 (Secondary), Number, percentage of participants: Adult Tablet,12-17 YR, ≥ 45 kg, ALT Normalization 87.5 (69.0 to 95.7); Mini-tablet, 9-11 YR, 15 to 29 kg, ALT Normalization 100 (20.7 to 100.0); Mini-tablet, 9-11 YR, 30 to 44 kg, ALT Normalization 100 (56.6 to 100.0); Mini-tablet, 3-8 YR, 15 to 29 kg, ALT Normalization 80.0 (49.0 to 94.3); Mini-tablet Total, ALT Normalization 87.5 (64.0 to 96.5); Participants in Parts 1 and 2 of the Study, ALT Normalization 87.5 (73.9 to 94.5)

Adverse events

Time frame: Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 37 weeks. SAEs and protocol-related nonserious AEs were collected from the time the subject signed consent.

Serious adverse events by term

Other adverse events by term

17 more terms not shown.

• Results publication: Rosenthal P, Narkewicz MR, Yao BB, Jolley CD, Lobritto SJ, Wen J, Molleston JP, Hsu EK, Jonas MM, Zha J, Liu L, Leung DH. Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir Mini-Tabs Plus Ribavirin for Children Aged 3-11 Years with Hepatitis C Genotype 1a. Adv Ther. 2020 Jul;37(7):3299-3310. doi: 10.1007/s12325-020-01389-9. Epub 2020 May 25. PMID 32451952

• Study Protocol (PDF, 2017-08-21)
• Statistical Analysis Plan (PDF, 2018-05-31)

• AbbVie Inc., Study director, AbbVie

NIH grants: 2015