Study to Investigate Pharmacokinetics, Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) Fixed Dose Combination (FDC) in Adolescents and Children With Chronic Hepatitis C Virus (HCV) Infection

Treatment-emergent Adverse Events (TEAE) were defined as events that met 1 or both of the following criteria as any AEs with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of study drug. It also includes the AEs that leads to premature discontinuation of study drug.

SVR was defined as hepatitis C virus (HCV RNA) < Lower limit of quantification (LLOQ) (ie, < 15 IU/mL) 12 weeks after discontinuation of the study drug.

SVR was defined as HCV RNA < LLOQ (ie, < 15 IU/mL) 4 weeks after discontinuation of the study drug.

SVR was defined as HCV RNA < LLOQ (ie, < 15 IU/mL) 24 weeks after discontinuation of the study drug.

Overall Virologic Failure comprises of on-treatment virologic failure and relapse. On-treatment virologic failure (breakthrough, rebound, and nonresponse) and relapse were defined as follows: Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), Rebound (confirmed > 1 log10IU/mL increase in HCV RNA from nadir while on treatment), or Nonresponse (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) and Relapse (confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on treatment visit).

Percentage of participants with HCV RNA < LLOQ (15 IU/mL) while on treatment by analysis visit.

Plasma samples were collected and stored for potential HCV sequencing. Impact on the treatment outcomes of SVR12 and SVR24 were observed during the study. Baseline nonstructural protein (NS)3, NS5A, and NS5B deep sequencing analysis was performed for all participants. Sequencing for the HCV NS5A and NS5B regions was performed for all enrolled participants at baseline and for participants with virologic failure.

Plasma samples were collected and stored for potential HCV sequencing. Impact on the treatment outcomes of SVR12 and SVR24 were observed during the study. Baseline nonstructural protein (NS)3, NS5A, and NS5B deep sequencing analysis was performed for all participants. Sequencing for the HCV NS5A and NS5B regions was performed for all enrolled participants at baseline and for participants with virologic failure.

ALT normalization was defined as ALT > upper limit of normal (ULN) at baseline and ALT ≤ ULN at each visit.

An age- and sex-specific percentile was derived for each weight, height, and body mass index (BMI) measurement according to the statistical analysis system (SAS) program available on the Centers for Disease Control and Prevention (CDC) website using the year 2000 growth charts.

An age- and sex-specific percentile was derived for each weight, height, and body mass index (BMI) measurement according to the statistical analysis system (SAS) program available on the Centers for Disease Control and Prevention (CDC) website using the year 2000 growth charts.

Tanner Pubertal Staging were assessed for pubic hair growth and genitalia development (males) and for pubic hair growth and breast development (females) in stages 1 to 5. Tanner stages will be used to evaluate the onset and progression of pubertal changes from stage 1 (pre-pubertal) to stage 5 (adult). If a participant had reached Tanner stage 5, no further Tanner pubertal stage assessments were to be completed.Pubic hair growth: Tanner stages (1: No hair, 2: Downy hair, 3: More coarse and curly hair, 4: Adult-like hair quality; 5: Hair extends to medial surface of the thighs); Breast development: Tanner stages (1: No glandular tissue, 2: Breast bud forms,3: More elevated, outside areola, 4: Increased breast size,5: Final adult-size breasts); Genitalia development: Tanner stages (1: Testes, scrotum, and penis about same size, 2: Enlargement of scrotum and testes, Penis (10.5-12.5); 3: Enlargement of penis (11.5-14); 4: Penis size (13.5-15); 5: Genitalia adult in size and shape).

For radiographic bone age assessment, a single x-ray of the left wrist, hand, and fingers was performed and assessed by changes from baseline through end of treatment period.

Fasting blood samples for baseline values for bone age biomarkers CTX and change from baseline were recorded.

Fasting blood samples for baseline values for bone age biomarkers P1NP and change from baseline were recorded.

Swallowability for SOF/VEL/VOX FDC placebo to match (PTM) tablets was summarized based on the participants present in each swallowability category of Able to Swallow or Unable to Swallow a placebo tablet on one occasion during screening until Day 1.

A questionnaire was administered to participants to assess acceptability, including palatability, of the formulation. Acceptability and palatability were assessed by questions about how the study drug tasted, how easy it was to swallow the study drug, and also at the end of treatment about how it was to take the study drug and, as they all received a single tablet daily, how they felt about the number of tablets they had to swallow.

A questionnaire was administered to the parent/legal guardian of participants to assess acceptability, including palatability, of the formulation. Acceptability and palatability were assessed by questions about how the study drug tasted, how easy it was to swallow the study drug, about how it was to take the study drug and, as they all received a single tablet daily, how they felt about the number of tablets they had to swallow.

Neuropsychiatric safety assessment was done using the Pediatric Quality of Life (PedsQL™ 4.0 SF15). The PedsQL™ 4.0 SF15 Questionnaires was completed by all participants. It is a comprehensive and widely used patient-reported outcome survey designed to measure health-related quality of life in healthy children and adolescents. It is presented for each of the 4 domains of the SF-15 (physical functioning, emotional functioning, social functioning, and school functioning), the psychosocial health summary (emotional, social, and school functioning domains), physical health summary and the Total Score. Total scores as well as each of the subscale scores are transformed on a scale from 0 to 100. Higher scores in each case indicate better health-related quality of life (HRQOL). A positive change from end of treatment period indicates improvement.

Neuropsychiatric safety assessment was done using the Pediatric Quality of Life (PedsQL™ 4.0 SF15). The PedsQL™ 4.0 SF15 Questionnaires was completed by the parent/ legal guardian of the participants. It is a comprehensive and widely used patient-reported outcome survey designed to measure health-related quality of life in healthy children and adolescents. It is presented for each of the 4 domains of the SF-15 (physical functioning, emotional functioning, social functioning, and school functioning), the psychosocial health summary (emotional, social, and school functioning domains), physical health summary and the Total Score. Total scores as well as each of the subscale scores are transformed on a scale from 0 to 100. Higher scores in each case indicate better HRQOL. A positive change from end of treatment period indicates improvement.

Neuropsychiatric safety assessment was done using the Pediatric Quality of Life (PedsQL™ 4.0 SF15). The PedsQL™ 4.0 SF15 Questionnaires was completed by all the participants. It is a comprehensive and widely used patient-reported outcome survey designed to measure health-related quality of life in healthy children and adolescents. It was presented for each of the 4 domains of the SF-15 (physical functioning, emotional functioning, social functioning, and school functioning), the psychosocial health summary (emotional, social, and school functioning domains), physical health summary and the Total Score. Total scores as well as each of the subscale scores are transformed on a scale from 0 to 100. Higher scores in each case indicate better HRQOL. A positive change from baseline indicates improvement.

Neuropsychiatric safety assessment was done using the Pediatric Quality of Life (PedsQL™ 4.0 SF15). The PedsQL™ 4.0 SF15 Questionnaires was completed by the parent/ legal guardian of the participants. It is a comprehensive and widely used patient-reported outcome survey designed to measure health-related quality of life in healthy children and adolescents. It is presented for each of the 4 domains of the SF-15 (physical functioning, emotional functioning, social functioning, and school functioning), the psychosocial health summary (emotional, social, and school functioning domains), physical health summary and the Total Score. Total scores as well as each of the subscale scores are transformed on a scale from 0 to 100. Higher scores in each case indicate better HRQOL. A positive change from baseline indicates improvement.