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

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03820258
• Collaborator: (none)
• Enrollment: 21
• Locations: 10
• Arms: 6
• Actual Duration (Months): 12.7
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the steady-state pharmacokinetics (PK) and confirm the age-appropriate dose of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose combination (FDC) in pediatric participants with chronic hepatitis C virus (HCV) infection.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Virus Infection	Drug: SOF/VEL/VOX	Phase 2

Detailed Description

Participants will receive placebo to match SOF/VEL/VOX FDC to assess ability to swallow tablets at screening up to Day 1.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label, Multicenter, Multi-cohort Study to Investigate the Pharmacokinetics, Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir Fixed Dose Combination in Adolescents and Children With Chronic HCV Infection
• Actual Study Start Date: Jan 28, 2019
• Actual Primary Completion Date: Dec 4, 2019
• Actual Study Completion Date: Feb 19, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: Cohort 1 (12 to < 18 years old), 8 Weeks Direct-acting antiviral (DAA)-naive participants without cirrhosis in Cohort 1 (12 to < 18 years old) will receive SOF/VEL/VOX FDC 400/100/100 mg for 8 weeks.	Drug: SOF/VEL/VOX; Administered once daily with food.; Other Names: Vosevi ®
Experimental: Experimental: Cohort 1 (12 to < 18 years old), 12 Weeks DAA-naive participants with cirrhosis or DAA-experienced participants with or without cirrhosis in Cohort 1 (12 to < 18 years old) will receive SOF/VEL/VOX FDC 400/100/100 mg for 12 weeks.	Drug: SOF/VEL/VOX; Administered once daily with food.; Other Names: Vosevi ®
Experimental: Experimental: Cohort 2 (6 to < 12 years old), 8 Weeks DAA-naive participants without cirrhosis in Cohort 2 (6 to < 12 years old) will receive SOF/VEL/VOX FDC for 8 weeks.	Drug: SOF/VEL/VOX; Administered once daily with food.; Other Names: Vosevi ®
Experimental: Experimental: Cohort 2 (6 to < 12 years old), 12 Weeks DAA-naive participants with cirrhosis or DAA-experienced participants with or without cirrhosis in Cohort 2 (6 to < 12 years old) will receive SOF/VEL/VOX FDC for 12 weeks.	Drug: SOF/VEL/VOX; Administered once daily with food.; Other Names: Vosevi ®
Experimental: Experimental: Cohort 3 (3 to < 6 years old), 8 Weeks DAA-naive participants without cirrhosis in Cohort 3 (6 to < 12 years old) will receive SOF/VEL/VOX FDC for 8 weeks.	Drug: SOF/VEL/VOX; Administered once daily with food.; Other Names: Vosevi ®
Experimental: Experimental: Cohort 3 (3 to < 6 years old), 12 Weeks DAA-naive participants with cirrhosis or DAA-experienced participants with or without cirrhosis in Cohort 3 (3 to < 6 years old) will receive SOF/VEL/VOX FDC for 12 weeks.	Drug: SOF/VEL/VOX; Administered once daily with food.; Other Names: Vosevi ®

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetic (PK) Parameter: AUCtau of SOF, GS-331007 (Metabolite of SOF), VEL, and VOX [Sparse PK Sample (all participants): At Weeks 1 and 8 at any time, Weeks 2 and 4 (predose and between 15 minutes and 4 hours postdose). Intensive PK Sample [PK Substudy (N=14)]: Week 2 or Week 4 (0 (predose), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose)]

   AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). For participants with separate consent to participate in the optional intensive PK substudy, intensive serial PK blood samples were collected at Week 2 or Week 4. Sparse PK samples were collected from all participants at Weeks 1, 2, 4, and end of treatment/Week 8. Plasma concentration data from all PK samples (intensive and sparse) were combined and used to generate PK parameters of SOF, GS-331007, VEL, and VOX for all participants using a population PK modeling approach.

Secondary Outcome Measures

1. Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event [First dose date up to the last dose date (maximum: 8 Weeks) plus 30 days]

   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.

2. Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [Posttreatment Week 12]

   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.

3. Percentage of Participants With HCV RNA < LLOQ 4 Weeks After Discontinuation of Therapy (SVR4) [Posttreatment Week 4]

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

4. Percentage of Participants With HCV RNA < LLOQ 24 Weeks After Discontinuation of Therapy (SVR24) [Posttreatment Week 24]

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

5. Percentage of Participants With Overall Virologic Failure [Up to Posttreatment Week 24]

   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).

6. Percentage of Participants With HCV RNA < LLOQ on Treatment [Weeks 1, 2, 4, and 8]

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

7. Percentage of Participants Who Developed Viral Resistance to SOF, VEL, and/or VOX During Treatment [Up to End of Treatment (Week 8)]

   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.

8. Percentage of Participants Who Developed Viral Resistance to SOF, VEL, and/or VOX When Treatment is Discontinued [Up to Posttreatment Week 24]

   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.

9. Change in HCV RNA From Day 1 Through End of Treatment [Baseline (Day 1); Weeks 1, 2 ,4, and 8]

10. Percentage of Participants With Alanine Aminotransferase (ALT) Normalization [Baseline (Day 1); Week 1, 2, 4, 8, and Posttreatment/Follow-up Week 4 (FU-4)]

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

11. Change From Baseline in Height Percentiles as a Measurement of Growth and Development [Baseline (Day 1); Weeks 1, 2, 4, 8, FU-4, Posttreatment/Follow-up Week 12 (FU-12), and Posttreatment/Follow-up Week 24 (FU-24)]

    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.

12. Change From Baseline in Weight Percentiles as a Measurement of Growth and Development [Baseline (Day 1); Weeks 1, 2, 4, 8, FU-4, FU-12, and FU-24]

    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.

13. Number of Participants by Tanner Stage Assessment as a Measurement of Growth and Development [Baseline (Day 1); Weeks 8, FU-12, and FU-24]

    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).

14. Change From Baseline in Radiographic Bone Age Assessment as a Measurement of Growth and Development [Baseline (Day 1); Week 8]

    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.

15. Change From Baseline in C-Type Collagen Sequence (CTX) Bone Turn-Over Biochemical Marker as a Measurement of Growth and Development [Baseline (Day 1); FU-24]

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

16. Change From Baseline in Procollagen Type 1 N-Terminal Propeptide (P1NP) Bone Turn-Over Biochemical Marker as a Measurement of Growth and Development [Baseline (Day 1); FU-24]

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

17. Percentage of Participants in Each Swallowability Category of Able to Swallow or Unable to Swallow SOF/VEL/VOX 400/100/100 mg Size Tablets [Baseline (Day 1)]

    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.

18. Percentage of Participants With Acceptability Questionnaire Responses as Assessed by the Study Participant [Baseline (Day 1); Week 8]

    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.

19. Percentage of Participants With Acceptability Questionnaire Responses as Assessed by the Parent/Legal Guardian [Week 8]

    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.

20. Neuropsychiatric Assessments Based on Questionnaire as Completed by Participant [Weeks 8, FU-12, and FU-24]

    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.

21. Neuropsychiatric Assessments Based on Questionnaire as Completed by Parent/Legal Guardian [Weeks 8, FU-12, and FU-24]

    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.

22. Change From Baseline in Neuropsychiatric Assessments as Completed by Participant [Baseline (Day 1); Weeks 8, FU-12, and FU-24]

    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.

23. Change From Baseline in Neuropsychiatric Assessments as Completed by Parent/Legal Guardian [Baseline (Day 1); Weeks 8, FU-12, and FU-24]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Consent of parent or legal guardian required

• Chronic HCV infection

• Screening laboratory values within defined thresholds

• Individuals must have a determination of prior treatment status:

• DAA-naive is defined as either:

• Treatment naive with no prior exposure to any interferon (IFN), ribavirin (RBV), or approved or experimental HCV-specific DAA

• Treatment experienced with an IFN-based regimen and no prior exposure to an approved or experimental HCV-specific DAA

• DAA-experienced is defined as prior exposure to a regimen including any DAA (eg, non-structural protein (NS)3/4A protease inhibitor, NS5A inhibitor, or NS5B nucleotide/nucleoside inhibitor)

Key Exclusion Criteria:

• History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol

• Co-infection with human immunodeficiency virus (HIV), acute hepatitis A virus (HAV) or hepatitis B virus (HBV)

• Clinical hepatic decompensation (eg, clinical ascites, encephalopathy, and/or variceal hemorrhage)

• Pregnant or nursing females

• Known hypersensitivity to study medication

• Use of any prohibited concomitant medications as within 28 days of the Day 1 visit

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SOS-intraSOC Epatologia	Firenze		Italy	50139
2	US Infettivologia Pediatrica-Polo Universitario	Milano		Italy	20157
3	Servizio di Epatologia e Nutrizione Pediatrica	Milan		Italy	20122
4	UOS Epatologia Pediatrica	Napoli		Italy	80131
5	UOSD Epatologia	San Giovanni Rotondo		Italy	71013
6	Wojewodzki Szpital	Bydgoszcz		Poland	85-030
7	Med Polonia	Poznan		Poland	60-693
8	Uniwersytecki Szpital Kliniczny im.	Wroclaw		Poland	50-368
9	Birmingham Women's and Children's NHS Foundation Trust	Birmingham		United Kingdom	B4 6NH
10	Kings Healthcare NHS Trust Hospital	London		United Kingdom	SE5 9RS

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Statistical Analysis Plan - Apr 10, 2020
• Study Protocol - Mar 27, 2019

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT03820258
• Other Study ID Numbers: GS-US-367-1175; 2018-000480-87
• First Posted: Jan 29, 2019
• Last Update Posted: Oct 23, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in Europe. The first participant was screened on 28 January 2019. The last study visit occurred on 19 February 2020.
Pre-assignment Detail	The study was terminated because EMA granted Gilead a waiver for SOF/VEL/VOX in children less than 12 years old. Cohorts 2 and 3 were not enrolled. As per the protocol, participants could have received 8 or 12 weeks of treatment, depending on their prior treatment and disease status, however all participants received treatment for 8 weeks.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Period Title: Overall Study
STARTED	21
COMPLETED	21
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Overall Participants	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14 (1.2)
Sex: Female, Male (Count of Participants)
Female	13 61.9%
Male	8 38.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 9.5%
Not Hispanic or Latino	19 90.5%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	16 76.2%
Black or African American	1 4.8%
Asian	2 9.5%
Other	2 9.5%
American Indian or Alaska Native	0 0%
Native Hawaiian or Pacific Islander	0 0%
Region of Enrollment (Count of Participants)
Italy	13 61.9%
Poland	4 19%
United Kingdom	4 19%
Cirrhosis (Count of Participants)
Yes	0 0%
No	21 100%
Baseline HCV Ribonucleic acid (RNA) (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	5.9 (0.70)
Baseline Alanine aminotransferase (ALT) Category (Count of Participants)
≤ 1.5 x (Upper Limit of Normal) ULN	16 76.2%
> 1.5 x ULN	5 23.8%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetic (PK) Parameter: AUCtau of SOF, GS-331007 (Metabolite of SOF), VEL, and VOX
Description	AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). For participants with separate consent to participate in the optional intensive PK substudy, intensive serial PK blood samples were collected at Week 2 or Week 4. Sparse PK samples were collected from all participants at Weeks 1, 2, 4, and end of treatment/Week 8. Plasma concentration data from all PK samples (intensive and sparse) were combined and used to generate PK parameters of SOF, GS-331007, VEL, and VOX for all participants using a population PK modeling approach.
Time Frame	Sparse PK Sample (all participants): At Weeks 1 and 8 at any time, Weeks 2 and 4 (predose and between 15 minutes and 4 hours postdose). Intensive PK Sample [PK Substudy (N=14)]: Week 2 or Week 4 (0 (predose), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose)

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Analysis Set included all enrolled adolescent participants who received at least 1 dose of study drug and for whom at least 1 nonmissing PK concentration value was available from all types of PK sampling.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
SOF	2474.8 (1247.28)
GS- 331007 (metabolite of SOF)	14890.2 (3126.35)
VEL	6773.0 (2367.30)
VOX	2205.8 (1403.45)

2. Secondary Outcome

Title	Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event
Description	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.
Time Frame	First dose date up to the last dose date (maximum: 8 Weeks) plus 30 days

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included participants who received at least 1 dose of study drug.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Number [percentage of participants]	0 0%

3. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Description	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.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

The Full Analysis Set included all adolescent participants 12 to < 18 years old who were enrolled into the study and took at least 1 dose of study drug (SOF/VEL/VOX FDC).

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Number (95% Confidence Interval) [percentage of participants]	100.0 476.2%

4. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ 4 Weeks After Discontinuation of Therapy (SVR4)
Description	SVR was defined as HCV RNA < LLOQ (ie, < 15 IU/mL) 4 weeks after discontinuation of the study drug.
Time Frame	Posttreatment Week 4

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Number (95% Confidence Interval) [percentage of participants]	100.0 476.2%

5. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ 24 Weeks After Discontinuation of Therapy (SVR24)
Description	SVR was defined as HCV RNA < LLOQ (ie, < 15 IU/mL) 24 weeks after discontinuation of the study drug.
Time Frame	Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Number (95% Confidence Interval) [percentage of participants]	100.0 476.2%

6. Secondary Outcome

Title	Percentage of Participants With Overall Virologic Failure
Description	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).
Time Frame	Up to Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Number [percentage of participants]	0 0%

7. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ on Treatment
Description	Percentage of participants with HCV RNA < LLOQ (15 IU/mL) while on treatment by analysis visit.
Time Frame	Weeks 1, 2, 4, and 8

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Week 1	52.4 249.5%
Week 2	81.0 385.7%
Week 4	90.5 431%
Week 8	100.0 476.2%

8. Secondary Outcome

Title	Percentage of Participants Who Developed Viral Resistance to SOF, VEL, and/or VOX During Treatment
Description	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.
Time Frame	Up to End of Treatment (Week 8)

Outcome Measure Data

Analysis Population Description

Resistance Analysis Population was defined as all participants in the Safety Analysis Set with a virologic outcome. No on-treatment virologic breakthrough or relapse was observed. Therefore, no participants qualified for resistance testing.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Number [percentage of participants]	0 0%

9. Secondary Outcome

Title	Percentage of Participants Who Developed Viral Resistance to SOF, VEL, and/or VOX When Treatment is Discontinued
Description	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.
Time Frame	Up to Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Resistance Analysis Population was defined as all participants in the Safety Analysis Set with a virologic outcome. No on-treatment virologic breakthrough or relapse was observed through posttreatment Week 12 or posttreatment Week 24.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Number [percentage of participants]	0 0%

10. Secondary Outcome

Title	Change in HCV RNA From Day 1 Through End of Treatment
Time Frame	Baseline (Day 1); Weeks 1, 2 ,4, and 8

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Change at Week 1	-4.55 (0.525)
Change at Week 2	-4.65 (0.621)
Change at Week 4	-4.71 (0.661)
Change at Week 8	-4.77 (0.698)

11. Secondary Outcome

Title	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization
Description	ALT normalization was defined as ALT > upper limit of normal (ULN) at baseline and ALT ≤ ULN at each visit.
Time Frame	Baseline (Day 1); Week 1, 2, 4, 8, and Posttreatment/Follow-up Week 4 (FU-4)

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed. It includes participants with ALT >ULN at Baseline.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	5
Week 1	50.0 238.1%
Week 2	75.0 357.1%
Week 4	100.0 476.2%
Week 8	100.0 476.2%
FU-4	100.0 476.2%

12. Secondary Outcome

Title	Change From Baseline in Height Percentiles as a Measurement of Growth and Development
Description	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.
Time Frame	Baseline (Day 1); Weeks 1, 2, 4, 8, FU-4, Posttreatment/Follow-up Week 12 (FU-12), and Posttreatment/Follow-up Week 24 (FU-24)

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Baseline	47.9
Change at Week 8	0.0
Change at FU-12	0.0
Change at FU-24	-0.2

13. Secondary Outcome

Title	Change From Baseline in Weight Percentiles as a Measurement of Growth and Development
Description	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.
Time Frame	Baseline (Day 1); Weeks 1, 2, 4, 8, FU-4, FU-12, and FU-24

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Baseline	54.0
Change at Week 8	-2.5
Change at FU-12	-2.7
Change at FU-24	-1.6

14. Secondary Outcome

Title	Number of Participants by Tanner Stage Assessment as a Measurement of Growth and Development
Description	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).
Time Frame	Baseline (Day 1); Weeks 8, FU-12, and FU-24

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Stage 1	1 4.8%
Stage 2	1 4.8%
Stage 3	0 0%
Stage 4	4 19%
Stage 5	2 9.5%
Stage 1	0 0%
Stage 2	2 9.5%
Stage 3	0 0%
Stage 4	4 19%
Stage 5	2 9.5%
Stage 1	0 0%
Stage 2	2 9.5%
Stage 3	0 0%
Stage 4	3 14.3%
Stage 5	3 14.3%
Stage 1	0 0%
Stage 2	1 4.8%
Stage 3	1 4.8%
Stage 4	2 9.5%
Stage 5	4 19%
Stage 1	1 4.8%
Stage 2	1 4.8%
Stage 3	0 0%
Stage 4	4 19%
Stage 5	2 9.5%
Stage 1	0 0%
Stage 2	2 9.5%
Stage 3	0 0%
Stage 4	4 19%
Stage 5	2 9.5%
Stage 1	0 0%
Stage 2	2 9.5%
Stage 3	0 0%
Stage 4	3 14.3%
Stage 5	3 14.3%
Stage 1	0 0%
Stage 2	1 4.8%
Stage 3	1 4.8%
Stage 4	2 9.5%
Stage 5	4 19%
Stage 1	0 0%
Stage 2	2 9.5%
Stage 3	2 9.5%
Stage 4	5 23.8%
Stage 5	4 19%
Stage 1	0 0%
Stage 2	2 9.5%
Stage 3	1 4.8%
Stage 4	5 23.8%
Stage 5	5 23.8%
Stage 1	0 0%
Stage 2	2 9.5%
Stage 3	1 4.8%
Stage 4	5 23.8%
Stage 5	5 23.8%
Stage 1	0 0%
Stage 2	1 4.8%
Stage 3	2 9.5%
Stage 4	4 19%
Stage 5	6 28.6%
Stage 1	0 0%
Stage 2	2 9.5%
Stage 3	2 9.5%
Stage 4	4 19%
Stage 5	5 23.8%
Stage 1	0 0%
Stage 2	2 9.5%
Stage 3	1 4.8%
Stage 4	5 23.8%
Stage 5	5 23.8%
Stage 1	0 0%
Stage 2	2 9.5%
Stage 3	1 4.8%
Stage 4	5 23.8%
Stage 5	5 23.8%
Stage 1	0 0%
Stage 2	1 4.8%
Stage 3	2 9.5%
Stage 4	4 19%
Stage 5	6 28.6%

15. Secondary Outcome

Title	Change From Baseline in Radiographic Bone Age Assessment as a Measurement of Growth and Development
Description	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.
Time Frame	Baseline (Day 1); Week 8

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Baseline	14.5
Change at Week 8	0.0

16. Secondary Outcome

Title	Change From Baseline in C-Type Collagen Sequence (CTX) Bone Turn-Over Biochemical Marker as a Measurement of Growth and Development
Description	Fasting blood samples for baseline values for bone age biomarkers CTX and change from baseline were recorded.
Time Frame	Baseline (Day 1); FU-24

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Baseline	1.35
Change at FU-24	-0.22

17. Secondary Outcome

Title	Change From Baseline in Procollagen Type 1 N-Terminal Propeptide (P1NP) Bone Turn-Over Biochemical Marker as a Measurement of Growth and Development
Description	Fasting blood samples for baseline values for bone age biomarkers P1NP and change from baseline were recorded.
Time Frame	Baseline (Day 1); FU-24

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	20
Baseline	383.25
Change at FU-24	-101.50

18. Secondary Outcome

Title	Percentage of Participants in Each Swallowability Category of Able to Swallow or Unable to Swallow SOF/VEL/VOX 400/100/100 mg Size Tablets
Description	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.
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Able to Swallow PTM Tablet	100.0 476.2%
Unable to Swallow PTM Tablet	0 0%

19. Secondary Outcome

Title	Percentage of Participants With Acceptability Questionnaire Responses as Assessed by the Study Participant
Description	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.
Time Frame	Baseline (Day 1); Week 8

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Did Not Taste Study Drug; Day 1	23.8 113.3%
Taste (Very Bad); Day 1	9.5 45.2%
Taste (Bad); Day 1	9.5 45.2%
Taste (Maybe Bad/ Maybe Good); Day 1	38.1 181.4%
Taste (Good); Day 1	19.0 90.5%
Taste (Very Good); Day 1	0 0%
Swallow (Very Hard); Day 1	9.5 45.2%
Swallow (Hard); Day 1	9.5 45.2%
Swallow (Maybe Hard/ Maybe Easy); Day 1	9.5 45.2%
Swallow (Easy); Day 1	23.8 113.3%
Swallow (Very Easy); Day 1	47.6 226.7%
Did Not Taste Study Drug; Week 8	25.0 119%
Taste (Very Bad); Week 8	0 0%
Taste (Bad); Week 8	25.0 119%
Taste (Maybe Bad/ Maybe Good); Week 8	40.0 190.5%
Taste (Good); Week 8	5.0 23.8%
Taste (Very Good); Week 8	5.0 23.8%
Swallow (Very Hard); Week 8	0 0%
Swallow (Hard); Week 8	5.0 23.8%
Swallow (Maybe Hard/ Maybe Easy); Week 8	20.0 95.2%
Swallow (Easy); Week 8	25.0 119%
Swallow (Very Easy); Week 8	50.0 238.1%
Take (Very Hard); Week 8	0 0%
Take (Hard); Week 8	0 0%
Take (Maybe Hard/Maybe Easy); Week 8	25.0 119%
Take (Easy); Week 8	50.0 238.1%
Take (Very Easy); Week 8	25.0 119%
Number of Tablets(Very Hard); Week 8	0 0%
Number of Tablets(Hard); Week 8	0 0%
Number of Tablets( Maybe Hard/ Maybe Easy); Week 8	45.0 214.3%
Number of Tablets(Easy); Week 8	25.0 119%
Number of Tablets(Very Easy); Week 8	30.0 142.9%

20. Secondary Outcome

Title	Percentage of Participants With Acceptability Questionnaire Responses as Assessed by the Parent/Legal Guardian
Description	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.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Did Not Taste Study Drug	61.9 294.8%
Taste (Very Bad)	0 0%
Taste (Bad)	23.8 113.3%
Taste (Maybe Bad/ Maybe Good)	9.5 45.2%
Taste (Good)	4.8 22.9%
Taste (Very Good)	0 0%
Swallow (Very Hard)	4.8 22.9%
Swallow (Hard)	9.5 45.2%
Swallow (Maybe Hard/ Maybe Easy)	14.3 68.1%
Swallow (Easy)	33.3 158.6%
Swallow (Very Easy)	38.1 181.4%
Take (Very Hard)	0 0%
Take (Hard)	9.5 45.2%
Take (Maybe Hard/ Maybe Easy)	19.0 90.5%
Take (Easy)	47.6 226.7%
Take (Very Easy)	23.8 113.3%
Number of Tablets (Very Hard)	0 0%
Number of Tablets (Hard)	4.8 22.9%
Number of Tablets (Maybe Hard/Maybe Easy)	28.6 136.2%
Number of Tablets (Easy)	47.6 226.7%
Number of Tablets (Very Easy)	19.0 90.5%

21. Secondary Outcome

Title	Neuropsychiatric Assessments Based on Questionnaire as Completed by Participant
Description	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.
Time Frame	Weeks 8, FU-12, and FU-24

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Physical Functioning; Week 8	88.1 (17.06)
Physical Functioning; Change at FU-12	-0.7 (7.29)
Physical Functioning; Change at FU-24	-0.9 (6.40)
Emotional Functioning; Week 8	78.0 (19.33)
Emotional Functioning; Change at FU-12	-3.0 (21.43)
Emotional Functioning; Change at FU-24	-1.8 (18.56)
Social Functioning; Week 8	95.0 (10.95)
Social Functioning; Change at FU-12	-2.9 (8.67)
Social Functioning; Change at FU-24	-0.4 (6.88)
School Functioning; Week 8	80.2 (22.89)
School Functioning; Change at FU-12	-4.8 (18.37)
School Functioning; Change at FU-24	-3.6 (16.15)
Physical Health; Week 8	88.1 (17.06)
Physical Health ; Change at FU-12	-0.7 (7.29)
Physical Health; Change at FU-24	-0.9 (6.40)
Psychosocial Health; Week 8	83.6 (15.04)
Psychosocial Health; Change at FU-12	-3.6 (12.38)
Psychosocial Health; Change at FU-24	-2.4 (11.51)
Total Score; Week 8	85.1 (14.13)
Total Score; Change at FU-12	-2.6 (9.32)
Total Score; Change at FU-24	-1.9 (8.83)

22. Secondary Outcome

Title	Neuropsychiatric Assessments Based on Questionnaire as Completed by Parent/Legal Guardian
Description	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.
Time Frame	Weeks 8, FU-12, and FU-24

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Physical Functioning; Week 8	87.4 (17.29)
Physical Functioning; Change at FU-12	-2.5 (9.39)
Physical Functioning; Change at FU-24	-1.7 (12.97)
Emotional Functioning; Week 8	78.6 (21.06)
Emotional Functioning; Change at FU-12	-0.3 (22.53)
Emotional Functioning; Change at FU-24	-2.4 (17.95)
Social Functioning; Week 8	87.7 (17.80)
Social Functioning; Change at FU-12	4.2 (18.04)
Social Functioning; Change at FU-24	0.8 (14.41)
School Functioning; Week 8	74.2 (27.63)
School Functioning; Change at FU-12	3.3 (20.84)
School Functioning; Change at FU-24	3.2 (16.77)
Physical Health; Week 8	87.4 (17.29)
Physical Health ; Change at FU-12	-2.5 (9.39)
Physical Health; Change at FU-24	-1.7 (12.97)
Psychosocial Health; Week 8	80.0 (17.46)
Psychosocial Health; Change at FU-12	2.1 (15.82)
Psychosocial Health; Change at FU-24	0.2 (9.61)
Total Score; Week 8	82.5 (16.10)
Total Score; Change at FU-12	0.6 (12.67)
Total Score; Change at FU-24	-0.4 (7.87)

23. Secondary Outcome

Title	Change From Baseline in Neuropsychiatric Assessments as Completed by Participant
Description	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.
Time Frame	Baseline (Day 1); Weeks 8, FU-12, and FU-24

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	21
Physical Functioning; Baseline	90.7 (13.81)
Physical Functioning; Change at Week 8	-2.6 (10.20)
Physical Functioning; Change at FU-12	-3.3 (11.87)
Physical Functioning; Change at FU-24	-3.5 (12.72)
Emotional Functioning; Baseline	73.2 (20.07)
Emotional Functioning; Change at Week 8	4.8 (10.63)
Emotional Functioning; Change at FU-12	1.8 (19.78)
Emotional Functioning; Change at FU-24	3.0 (15.64)
Social Functioning; Baseline	93.3 (12.53)
Social Functioning; Change at Week 8	0.4 (9.16)
Social Functioning; Change at FU-12	-2.0 (10.17)
Social Functioning; Change at FU-24	-0.8 (8.70)
School Functioning; Baseline	75.0 (24.58)
School Functioning; Change at Week 8	5.2 (17.97)
School Functioning; Change at FU-12	0.4 (12.21)
School Functioning; Change at FU-24	1.6 (11.06)
Physical Health; Baseline	90.7 (13.81)
Physical Health; Change at Week 8	-2.6 (10.20)
Physical Health; Change at FU-12	-3.3 (11.87)
Physical Health, Change at FU-24	-3.5 (12.72)
Psychosocial Health; Baseline	79.8 (14.16)
Psychosocial Health; Change at Week 8	3.8 (7.47)
Psychosocial Health; Change at FU-12	0.2 (9.74)
Psychosocial Health; Change at FU-24	1.4 (8.81)
Total Score; Baseline	83.4 (12.40)
Total Score; Change at Week 8	1.7 (5.30)
Total Score; Change at FU-12	-1.0 (8.83)
Total Score; Change at FU-24	-0.2 (8.58)

24. Secondary Outcome

Title	Change From Baseline in Neuropsychiatric Assessments as Completed by Parent/Legal Guardian
Description	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.
Time Frame	Baseline (Day 1); Weeks 8, FU-12, and FU-24

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
Measure Participants	20
Physical Functioning; Baseline	85.3 (22.56)
Physical Functioning; Change at Week 8	3.5 (20.97)
Physical Functioning; Change at FU-12	2.1 (20.90)
Physical Functioning; Change at FU-24	4.0 (19.97)
Emotional Functioning; Baseline	73.4 (18.57)
Emotional Functioning; Change at Week 8	7.8 (18.57)
Emotional Functioning; Change at FU-12	6.6 (14.50)
Emotional Functioning; Change at FU-24	4.7 (12.80)
Social Functioning; Baseline	85.8 (18.36)
Social Functioning; Change at Week 8	1.3 (21.84)
Social Functioning; Change at FU-12	6.1 (18.39)
Social Functioning; Change at FU-24	2.1 (21.27)
School Functioning; Baseline	72.5 (27.59)
School Functioning; Change at Week 8	0.4 (23.64)
School Functioning; Change at FU-12	3.9 (22.80)
School Functioning; Change at FU-24	3.8 (20.50)
Physical Health; Baseline	85.3 (22.56)
Physical Health; Change at Week 8	3.5 (20.97)
Physical Health; Change at FU-12	2.1 (20.90)
Physical Health, Change at FU-24	4.0 (19.97)
Psychosocial Health; Baseline	76.8 (17.34)
Psychosocial Health; Change at Week 8	3.7 (17.39)
Psychosocial Health; Change at FU-12	5.7 (15.31)
Psychosocial Health; Change at FU-24	3.7 (15.52)
Total Score; Baseline	79.7 (15.40)
Total Score; Change at Week 8	3.6 (15.84)
Total Score; Change at FU-12	4.5 (14.37)
Total Score; Change at FU-24	3.8 (14.89)

Adverse Events

Time Frame	First dose date up to the last dose date (maximum: 8 Weeks) plus 30 days
Adverse Event Reporting Description	The Safety Analysis Set included participants received at least 1 dose of study drug.
Arm/Group Title	SOF/VEL/VOX FDC
Arm/Group Description	Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets.
All Cause Mortality
	SOF/VEL/VOX FDC
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Serious Adverse Events
	SOF/VEL/VOX FDC
	Affected / at Risk (%)	# Events
Total	1/21 (4.8%)
Vascular disorders
Hypotension	1/21 (4.8%)
Other (Not Including Serious) Adverse Events
	SOF/VEL/VOX FDC
	Affected / at Risk (%)	# Events
Total	13/21 (61.9%)
Gastrointestinal disorders
Abdominal pain	5/21 (23.8%)
Diarrhoea	3/21 (14.3%)
Nausea	4/21 (19%)
General disorders
Asthenia	2/21 (9.5%)
Fatigue	3/21 (14.3%)
Infections and infestations
Rhinitis	3/21 (14.3%)
Nervous system disorders
Dizziness	2/21 (9.5%)
Headache	5/21 (23.8%)
Respiratory, thoracic and mediastinal disorders
Cough	2/21 (9.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years