Study to Investigate the Safety and Efficacy of Sofosbuvir/Velpatasvir in Adolescents and Children With Chronic HCV Infection

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03022981
• Collaborator: (none)
• Enrollment: 216
• Locations: 27
• Arms: 3
• Actual Duration (Months): 37
• Patients Per Site: 8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will have 2 parts: Pharmacokinetics (PK) Lead-in Phase and the Treatment Phase.

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

The primary objective of the Treatment Phase is to evaluate the safety and tolerability of SOF/VEL for 12 weeks in pediatric participants with chronic HCV.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 216 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label, Multicenter, Multi-cohort Study to Investigate the Safety and Efficacy of Sofosbuvir/Velpatasvir in Adolescents and Children With Chronic HCV Infection
• Actual Study Start Date: Jan 26, 2017
• Actual Primary Completion Date: Nov 19, 2019
• Actual Study Completion Date: Feb 26, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 12 to < 18 Years Old PK Lead-in Phase: Sofosbuvir/Velpatasvir (SOF/VEL) 400/100 mg once daily for 7 days. Participants who complete the PK lead-in phase, continue into the treatment phase with no interruption of study drug administration and additional participants will be enrolled into the treatment phase once the appropriateness of the dose is confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL 400/100 mg once daily for 12 weeks.	Drug: SOF/VEL; SOF/VEL fixed-dose combination (FDC) 400/100 mg tablets or SOF/VEL FDC 200/50 mg tablets (based on swallowability assessment); Other Names: Epclusa® GS-7977/GS-5816
Experimental: 6 to < 12 Years Old PK Lead-in Phase: SOF/VEL 200/50 mg once daily for 7 days. Participants who complete the PK lead-in phase, continue into the treatment phase with no interruption of study drug administration and additional participants will be enrolled into the treatment phase once the appropriateness of the dose is confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL 200/50 mg once daily for 12 weeks.	Drug: SOF/VEL; SOF/VEL fixed-dose combination (FDC) 400/100 mg tablets or SOF/VEL FDC 200/50 mg tablets (based on swallowability assessment); Other Names: Epclusa® GS-7977/GS-5816
Experimental: 3 to < 6 Years Old PK Lead-in Phase: SOF/VEL 200/50 mg once daily for 7 days for participants who weigh ≥ 17 kg. SOF/VEL 150/37.5 mg once daily for 7 days for participants who weigh < 17 kg. Participants who complete the PK lead-in phase, continue into the treatment phase with no interruption of study drug administration and additional participants will be enrolled into the treatment phase once the appropriateness of the dose is confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL 200/50 mg once daily for 12 weeks for participants who weigh ≥ 17 kg. SOF/VEL 150/37.5 mg once daily for 12 weeks for participants who weigh < 17 kg.	Drug: SOF/VEL; SOF/VEL FDC 200/50 mg oral granules; Other Names: Epclusa® GS-7977/GS-5816

Outcome Measures

Primary Outcome Measures

1. PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Velpatasvir (VEL) [Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose]

   AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).

2. PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Sofosbuvir (SOF) [Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose]

   AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).

3. PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of GS-331007 (Metabolite of SOF) [Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose]

   AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

4. Treatment Phase: Percentage of Participants Who Discontinued Study Drug Due to Any Treatment-Emergent Adverse Event (TEAE) [From first dose through last dose of the study drug (Up to 12 weeks) plus 30 days]

   An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or Any AEs leading to premature discontinuation of study drug.

Secondary Outcome Measures

1. PK Lead-in Phase: Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 7 [Baseline; Day 7]

2. PK Lead-in Phase: Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (AE) [First dose date up to Day 7]

   An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

3. Treatment Phase: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) [Posttreatment Week 12]

   SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

4. Treatment Phase: Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) [Posttreatment Week 4]

   SVR4 was defined as HCV RNA < LLOQ (ie, 15 IU/mL) at 4 weeks after stopping study treatment.

5. Treatment Phase: Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) [Posttreatment Week 24]

   SVR 24 was defined as HCV RNA < LLOQ (ie, 15 IU/mL) at 24 weeks after stopping study treatment.

6. Treatment Phase: Percentage of Participants With Virologic Failure [Up to Posttreatment Week 24]

   Virologic failure was defined as: On-treatment virologic failure - Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment); Virologic relapse: Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

7. Treatment Phase: Percentage of Participants With HCV RNA < LLOQ On Treatment [Weeks 1, 4, 8, and 12]

   Percentage of participants with HCV RNA < LLOQ while on treatment by analysis visit.

8. Treatment Phase: Percentage of Participants Who Develop Viral Resistance to SOF and/or VEL During Treatment and After Discontinuation of Treatment [First dose date up to Posttreatment Week 24]

   Drug-resistant substitutions were analyzed as part of the Virology Study. 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 deep sequencing of the HCV nonstructural protein (NS)5A and NS5B genes was performed for all participants at the first time point after virologic failure if the plasma or serum sample was available. Pretreatment full-length NS5A deep sequencing data were obtained at a 15% assay cutoff for the Resistance Analysis Population which covered all NS5A and NS5B nucleoside inhibitor (NI) resistance-associated variants (RAVs).

9. Treatment Phase: Change From Baseline in HCV RNA at Weeks 1, 4, 8, and 12 [Baseline; Weeks 1, 4, 8, and 12]

10. Treatment Phase: Quality of Life (QoL) and Neuropsychiatric Assessments as Measured by PedsQL™ Pediatric QoL Survey [Baseline; Week 12, End of Treatment (EOT), Posttreatment/Follow-up (FU) Week-12 (FU-12), and FU Week-24 (FU-24)]

    To evaluate the effect of treatment with SOF/VEL on general and disease-specific health-related QoL, the PedsQL™ Pediatric QoL Inventory V4.0 Short Form (SF15) was completed at Day 1, end of treatment, early termination (if applicable), and posttreatment Weeks 12 and 24. The SF15 questionnaire represented 4 domains: physical, emotional, social, and school functioning, with the emotional, social, and school functioning domains representing the psychosocial health summary. Neuropsychiatric assessment was conducted using the PedsQL™ Pediatric QoL Inventory V4.0 SF15 psychosocial domain-related scores. Items were calculated and transformed into an overall score with a range of 0 to 100 points, with more points indicating better QoL.

11. Treatment Phase: Change From Baseline in Growth and Development as Measured by Height Percentiles [Baseline; Weeks 1, 4, 8, 12, Follow-up (FU) Week 4 (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.

12. Treatment Phase: Change From Baseline in Growth and Development as Measured by Weight Percentiles [Baseline; Weeks 1, 4, 8, 12, FU-4, FU-12, and FU-24]

    An age- and sex-specific percentile was derived for each weight, height, and BMI measurement according to the SAS program available on the CDC website using the year 2000 growth charts.

13. Treatment Phase: Changes in Growth and Development as Measured by Tanner Stage Assessment From Baseline [Baseline; EOT, FU-12 and FU-24]

    Tanner Pubertal Staging was 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 were 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 the 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, testes and penis, 3: Enlargement of penis, 4: Penis size enlargement, 5: Genitalia adult in size and shape).

14. Treatment Phase: Growth and Development as Measured by Parental Height [Day 1]

    Mid-parental height was calculated as the average of the biological father's and mother's heights. For boys, the sex-adjusted mid-parental height was calculated by adding 2.5 inches or 6.5 cm to the mean of the parents' heights. For girls, 2.5 inches or 6.5 cm was subtracted from the mean of the parents' heights.

15. Treatment Phase: Change From Baseline in Growth and Development as Measured by Bone Age [Baseline; FU-24]

    Bone age was determined based on x-ray of the left wrist, hand, and fingers. Baseline value is the last available value on or prior to first dose date of study drug.

16. Treatment Phase: Swallowability of SOF/VEL as Assessed by the Participant's Ability to Swallow SOF/VEL Placebo Tablets at Baseline [Baseline]

    A SOF/VEL FDC swallowability assessment was performed using placebo tablets at baseline.

17. Treatment Phase: Number of Participants With Acceptability of SOF/VEL as Measured by a Questionnaire to Assess Acceptability, Including Palatability at Day 1 [Day 1]

    Acceptability was assessed by numeric response marked on line between numbers 0 - 100. Higher scores indicate better acceptability and/or palatability.

18. Treatment Phase: Number of Participants With Acceptability of SOF/VEL as Measured by a Questionnaire to Assess Acceptability, Including Palatability at Week 12 [Week 12]

    Acceptability was assessed by numeric response marked on line between numbers 0 - 100. Higher scores indicate better acceptability and/or palatability.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Chronic HCV-infected, treatment-naive and treatment-experienced adolescent and pediatric individuals aged 3 to < 18 as determined at Day 1.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
2	University of California, San Francisco	San Francisco	California	United States	94158
3	Children's Hospital of Colorado	Aurora	Colorado	United States	80045
4	Children's National Medical Center	Washington	District of Columbia	United States	20010
5	University of Florida Shands Medical	Gainesville	Florida	United States	32610
6	Florida Gastroenterology Care for Children	Orlando	Florida	United States	32803
7	Emory Children's Center	Atlanta	Georgia	United States	30322
8	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
9	Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky	United States	40202
10	Johns Hopkins University (JHU) - The Johns Hopkins Hospital (JHH)	Baltimore	Maryland	United States	21287
11	Boston Children's Hospital	Boston	Massachusetts	United States	02115
12	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
13	Children's Hospital & Medical Center	Omaha	Nebraska	United States	68198-5331
14	Mount Sinai Medical Center	New York	New York	United States	10029
15	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
16	Nationwide Children's Hospital- The Ohio State University (OSU)	Columbus	Ohio	United States	43205
17	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
18	Monroe Carell Jr. Children's Hospital at Vanderbilt	Nashville	Tennessee	United States	37232
19	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
20	Baylor College of Medicine	Houston	Texas	United States	77030
21	Seattle Children's Hospital	Seattle	Washington	United States	98105
22	Cliniques Universitaires Saint Luc	Brussels		Belgium	1200
23	Azienda Ospedaliero-Universitaria di Bologna - Policlinico S. Orsola - Malpighi	Bologna		Italy	40138
24	Azienda Ospedaliera Universitaria Meyer	Firenze		Italy	50139
25	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo		Italy	71013
26	The Leeds Teaching Hospitals NHS Trust	Leeds	England	United Kingdom	LS1 3EX
27	King's College Hospital NHS Trust	London	England	United Kingdom	SE5 9RS

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol - Jun 15, 2018
• Statistical Analysis Plan - Apr 20, 2020

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT03022981
• Other Study ID Numbers: GS-US-342-1143; 2016-002446-23
• First Posted: Jan 18, 2017
• Last Update Posted: Oct 8, 2020
• Last Verified: Oct 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
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis C; Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Velpatasvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at 28 study sites in Belgium, Italy, the United Kingdom, and the United States. The first participant was screened on 26 January 2017. The last study visit occurred on 26 February 2020.
Pre-assignment Detail	221 participants were screened.

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Pharmacokinetic (PK) Lead-in Phase: Sofosbuvir/Velpatasvir (SOF/VEL) fixed-dose combination (FDC) 400/100 mg tablets once daily for 7 days. Participants who completed the PK lead-in phase, continued into the treatment phase with no interruption of study drug administration and additional participants were enrolled into the treatment phase once the appropriateness of the dose was confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 7 days. Participants who completed the PK lead-in phase, continued into the treatment phase with no interruption of study drug administration and additional participants were enrolled into the treatment phase once the appropriateness of the dose was confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 7 days for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 7 days for participants who weighed < 17 kg. Participants who completed the PK lead-in phase, continued into the treatment phase with no interruption of study drug administration and additional participants were enrolled into the treatment phase once the appropriateness of the dose was confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Period Title: Overall Study
STARTED	102	73	41
Participated in PK Lead-in (PKL) Phase	17	20	19
COMPLETED	96	69	35
NOT COMPLETED	6	4	6

Baseline Characteristics

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old	Total
Arm/Group Description	PK Lead-in Phase: Sofosbuvir/Velpatasvir (SOF/VEL) fixed-dose combination (FDC) 400/100 mg tablets once daily for 7 days. Participants who completed the PK lead-in phase, continued into the treatment phase with no interruption of study drug administration and additional participants were enrolled into the treatment phase once the appropriateness of the dose was confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 7 days. Participants who completed the PK lead-in phase, continued into the treatment phase with no interruption of study drug administration and additional participants were enrolled into the treatment phase once the appropriateness of the dose was confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 7 days for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 7 days for participants who weighed < 17 kg. Participants who completed the PK lead-in phase, continued into the treatment phase with no interruption of study drug administration and additional participants were enrolled into the treatment phase once the appropriateness of the dose was confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.	Total of all reporting groups
Overall Participants	102	73	41	216
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15 (1.9)	8 (1.6)	4 (0.8)	10 (4.5)
Sex: Female, Male (Count of Participants)
Female	52 51%	38 52.1%	24 58.5%	114 52.8%
Male	50 49%	35 47.9%	17 41.5%	102 47.2%
Race/Ethnicity, Customized (Count of Participants)
White	74 72.5%	66 90.4%	32 78%	172 79.6%
Black or African American	9 8.8%	4 5.5%	3 7.3%	16 7.4%
Asian	11 10.8%	1 1.4%	0 0%	12 5.6%
Other	5 4.9%	2 2.7%	5 12.2%	12 5.6%
American Indian or Alaska Native	2 2%	0 0%	0 0%	2 0.9%
Not Permitted	1 1%	0 0%	1 2.4%	2 0.9%
Native Hawaiian or Pacific Islander	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	14 13.7%	7 9.6%	4 9.8%	25 11.6%
Not Hispanic or Latino	83 81.4%	64 87.7%	36 87.8%	183 84.7%
Not Permitted	5 4.9%	2 2.7%	1 2.4%	8 3.7%
Region of Enrollment (Count of Participants)
United States	77 75.5%	57 78.1%	38 92.7%	172 79.6%
Italy	17 16.7%	5 6.8%	2 4.9%	24 11.1%
United Kingdom	5 4.9%	9 12.3%	1 2.4%	15 6.9%
Belgium	3 2.9%	2 2.7%	0 0%	5 2.3%

Outcome Measures

1. Primary Outcome

Title	PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Velpatasvir (VEL)
Description	AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
Time Frame	Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose

Outcome Measure Data

Analysis Population Description

The Lead-in Phase Pharmacokinetic (PK) Analysis Set included all PK lead-in phase participants with available data who received at least 1 dose of study drug and whom at least one non-missing PK concentration data value is available from the PK Lead-in Phase intensive sampling.

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	PK Lead-in Phase: Sofosbuvir/Velpatasvir (SOF/VEL) fixed-dose combination (FDC) 400/100 mg tablets once daily for 7 days.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 7 days.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 7 days for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 7 days for participants who weighed < 17 kg.
Measure Participants	16	17	18
Mean (Standard Deviation) [hours*nanograms per milliliter (h*ng/mL)]	4479.3 (2105.66)	3697.5 (1653.25)	4450.3 (3285.75)

2. Primary Outcome

Title	PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Sofosbuvir (SOF)
Description	AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
Time Frame	Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose

Outcome Measure Data

Analysis Population Description

Participants in the Lead-in Phase PK Analysis Set with available data were analyzed.

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	Cohort 3 (3 to < 6 Years Old)
Arm/Group Description	PK Lead-in Phase: SOF/VEL FDC 400/100 mg tablets once daily for 7 days.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 7 days.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 7 days for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 7 days for participants who weighed < 17 kg.
Measure Participants	16	17	17
Mean (Standard Deviation) [h*ng/mL]	3020.1 (1162.56)	1764.5 (690.12)	3306.2 (3499.49)

3. Primary Outcome

Title	PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of GS-331007 (Metabolite of SOF)
Description	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame	Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose

Outcome Measure Data

Analysis Population Description

Participants in the Lead-in Phase PK Analysis Set with available data were analyzed.

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	PK Lead-in Phase: SOF/VEL FDC 400/100 mg tablets once daily for 7 days.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 7 days.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 7 days for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 7 days for participants who weighed < 17 kg.
Measure Participants	16	17	18
Mean (Standard Deviation) [h*ng/mL]	13852.9 (3565.85)	9913.8 (3071.79)	11604.0 (2732.57)

4. Primary Outcome

Title	Treatment Phase: Percentage of Participants Who Discontinued Study Drug Due to Any Treatment-Emergent Adverse Event (TEAE)
Description	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or Any AEs leading to premature discontinuation of study drug.
Time Frame	From first dose through last dose of the study drug (Up to 12 weeks) plus 30 days

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who were enrolled into the study and received at least 1 dose of study drug (SOF/VEL FDC).

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	102	73	41
Number [percentage of participants]	0.0 0%	2.7 3.7%	2.4 5.9%

5. Secondary Outcome

Title	PK Lead-in Phase: Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 7
Time Frame	Baseline; Day 7

Outcome Measure Data

Analysis Population Description

Participants in the Lead-in Phase PK Analysis Set with available data were analyzed.

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	PK Lead-in Phase: SOF/VEL FDC 400/100 mg tablets once daily for 7 days.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 7 days.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 7 days for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 7 days for participants who weighed < 17 kg.
Measure Participants	17	20	19
Baseline	6.09 (0.569)	5.84 (0.656)	5.77 (1.275)
Change from Baseline at Day 7	-4.48 (0.656)	-4.20 (0.642)	-3.94 (1.082)

6. Secondary Outcome

Title	PK Lead-in Phase: Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (AE)
Description	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame	First dose date up to Day 7

Outcome Measure Data

Analysis Population Description

Participants in the Lead-in Phase PK Analysis Set were analyzed.

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	PK Lead-in Phase: SOF/VEL FDC 400/100 mg tablets once daily for 7 days.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 7 days.	PK Lead-in Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 7 days for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 7 days for participants who weighed < 17 kg.
Measure Participants	17	20	19
Number [percentage of participants]	0.0 0%	0.0 0%	0.0 0%

7. Secondary Outcome

Title	Treatment Phase: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)
Description	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

The Full Analysis Set included all participants who were enrolled into the study and received at least 1 dose of study drug (SOF/VEL FDC).

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	102	73	41
Number (95% Confidence Interval) [percentage of participants]	95.1 93.2%	93.2 127.7%	82.9 202.2%

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	102	73	41
Number (95% Confidence Interval) [percentage of participants]	96.1 94.2%	94.5 129.5%	82.9 202.2%

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	102	73	41
Number (95% Confidence Interval) [percentage of participants]	95.1 93.2%	93.2 127.7%	82.9 202.2%

10. Secondary Outcome

Title	Treatment Phase: Percentage of Participants With Virologic Failure
Description	Virologic failure was defined as: On-treatment virologic failure - Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment); Virologic 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	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	102	73	41
Number [percentage of participants]	1.0 1%	1.4 1.9%	0.0 0%

11. Secondary Outcome

Title	Treatment Phase: Percentage of Participants With HCV RNA < LLOQ On Treatment
Description	Percentage of participants with HCV RNA < LLOQ while on treatment by analysis visit.
Time Frame	Weeks 1, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	102	73	41
Week 1	44.1 43.2%	39.7 54.4%	36.8 89.8%
Week 4	96.1 94.2%	94.4 129.3%	91.4 222.9%
Week 8	100.0 98%	98.6 135.1%	100.0 243.9%
Week 12	100.0 98%	98.6 135.1%	100.0 243.9%

12. Secondary Outcome

Title	Treatment Phase: Percentage of Participants Who Develop Viral Resistance to SOF and/or VEL During Treatment and After Discontinuation of Treatment
Description	Drug-resistant substitutions were analyzed as part of the Virology Study. 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 deep sequencing of the HCV nonstructural protein (NS)5A and NS5B genes was performed for all participants at the first time point after virologic failure if the plasma or serum sample was available. Pretreatment full-length NS5A deep sequencing data were obtained at a 15% assay cutoff for the Resistance Analysis Population which covered all NS5A and NS5B nucleoside inhibitor (NI) resistance-associated variants (RAVs).
Time Frame	First dose date up to Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

The Resistance Analysis Population with all adolescent or pediatric participants in the Safety Analysis Set with a virologic outcome with available data were analyzed.

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	98	68	33
Pretreatment NS5A NI RAVs	16.3 16%	10.2 14%	18.1 44.1%
Pretreatment NS5B NI RAVs	5.1 5%	0.0 0%	3.0 7.3%

13. Secondary Outcome

Title	Treatment Phase: Change From Baseline in HCV RNA at Weeks 1, 4, 8, and 12
Time Frame	Baseline; Weeks 1, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	102	73	41
Baseline	6.06 (0.585)	5.87 (0.686)	5.86 (1.057)
Change from Baseline at Week 1	-4.46 (0.661)	-4.28 (0.632)	-4.06 (0.914)
Change from Baseline at Week 4	-4.89 (0.578)	-4.64 (0.860)	-4.49 (1.040)
Change from Baseline at Week 8	-4.91 (0.588)	-4.69 (0.678)	-4.56 (1.066)
Change from Baseline at Week 12	-4.91 (0.588)	-4.70 (0.683)	-4.56 (1.066)

14. Secondary Outcome

Title	Treatment Phase: Quality of Life (QoL) and Neuropsychiatric Assessments as Measured by PedsQL™ Pediatric QoL Survey
Description	To evaluate the effect of treatment with SOF/VEL on general and disease-specific health-related QoL, the PedsQL™ Pediatric QoL Inventory V4.0 Short Form (SF15) was completed at Day 1, end of treatment, early termination (if applicable), and posttreatment Weeks 12 and 24. The SF15 questionnaire represented 4 domains: physical, emotional, social, and school functioning, with the emotional, social, and school functioning domains representing the psychosocial health summary. Neuropsychiatric assessment was conducted using the PedsQL™ Pediatric QoL Inventory V4.0 SF15 psychosocial domain-related scores. Items were calculated and transformed into an overall score with a range of 0 to 100 points, with more points indicating better QoL.
Time Frame	Baseline; Week 12, End of Treatment (EOT), Posttreatment/Follow-up (FU) Week-12 (FU-12), and FU Week-24 (FU-24)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	102	73	41
Parents Reports, Total Score at Baseline	80.0 (17.71)	79.7 (15.58)	86.5 (12.43)
Parents Reports, Total Score at Week 12	82.4 (18.13)	82.8 (14.26)	87.3 (11.31)
Parents Reports, Total Score at EOT	82.4 (18.13)	82.2 (14.95)	87.0 (11.65)
Parents Reports, Total Score at Follow Up-12	81.7 (17.39)	81.5 (15.34)	87.7 (14.11)
Parents Reports, Total Score at Follow Up-24	80.8 (18.65)	79.7 (15.30)	88.3 (9.79)
Participants Reports, Total Score at Baseline	79.9 (15.22)	77.9 (13.33)	82.2 (12.47)
Participants Reports, Total Score at Week 12	80.9 (16.38)	80.0 (14.21)	83.3 (11.62)
Participants Reports, Total Score at EOT	80.9 (16.38)	79.7 (14.13)	83.3 (11.62)
Participants Reports, Total Score at Follow Up-12	82.5 (15.41)	81.1 (13.32)	80.5 (14.18)
Participants Reports, Total Score at Follow Up-24	81.4 (16.34)	81.7 (15.43)	82.1 (12.56)

15. Secondary Outcome

Title	Treatment Phase: Change From Baseline in Growth and Development as Measured by Height Percentiles
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; Weeks 1, 4, 8, 12, Follow-up (FU) Week 4 (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	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	102	73	41
Baseline	44.5	41.9	39.3
Change From Baseline at Week 1	0.0	0.1	0.5
Change From Baseline at Week 4	0.0	0.2	1.4
Change From Baseline at Week 8	0.0	-0.1	0.3
Change From Baseline at Week 12	-0.1	0.2	0.2
Change From Baseline at FU-4	0.0	0.2	1.2
Change From Baseline at FU-12	-0.2	0.1	0.6
Change From Baseline at FU-24	-0.6	-0.2	0.3

16. Secondary Outcome

Title	Treatment Phase: Change From Baseline in Growth and Development as Measured by Weight Percentiles
Description	An age- and sex-specific percentile was derived for each weight, height, and BMI measurement according to the SAS program available on the CDC website using the year 2000 growth charts.
Time Frame	Baseline; Weeks 1, 4, 8, 12, 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	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	102	73	41
Baseline	67.2	45.9	64.6
Change From Baseline at Week 1	0.0	0.1	-0.5
Change From Baseline at Week 4	0.0	0.2	0.3
Change From Baseline at Week 8	0.0	0.1	0.2
Change From Baseline at Week 12	0.2	0.5	-1.7
Change From Baseline at FU-4	0.1	0.0	-0.8
Change From Baseline at FU-12	0.0	0.5	-0.8
Change From Baseline at FU-24	0.1	1.4	-1.3

17. Secondary Outcome

Title	Treatment Phase: Changes in Growth and Development as Measured by Tanner Stage Assessment From Baseline
Description	Tanner Pubertal Staging was 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 were 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 the 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, testes and penis, 3: Enlargement of penis, 4: Penis size enlargement, 5: Genitalia adult in size and shape).
Time Frame	Baseline; EOT, FU-12 and FU-24

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed. Overall Number of Participants Analyzed for each arm is the total of male plus female participants.

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	102	73	41
Pubic Hair (Male): Baseline, Stage 1	4 3.9%	31 42.5%	17 41.5%
Pubic Hair (Male): Baseline, Stage 2	3 2.9%	2 2.7%	0 0%
Pubic Hair (Male): Baseline, Stage 3	10 9.8%	1 1.4%	0 0%
Pubic Hair (Male): Baseline, Stage 4	14 13.7%	0 0%	0 0%
Pubic Hair (Male): Baseline, Stage 5	19 18.6%	0 0%	0 0%
Pubic Hair (Male): EOT, Stage 1	2 2%	28 38.4%	13 31.7%
Pubic Hair (Male): EOT, Stage 2	4 3.9%	3 4.1%	0 0%
Pubic Hair (Male): EOT, Stage 3	7 6.9%	1 1.4%	0 0%
Pubic Hair (Male): EOT, Stage 4	13 12.7%	0 0%	0 0%
Pubic Hair (Male): EOT, Stage 5	24 23.5%	0 0%	0 0%
Pubic Hair (Male): FU-12, Stage 1	1 1%	26 35.6%	14 34.1%
Pubic Hair (Male): FU-12, Stage 2	5 4.9%	3 4.1%	0 0%
Pubic Hair (Male): FU-12, Stage 3	6 5.9%	1 1.4%	0 0%
Pubic Hair (Male): FU-12, Stage 4	10 9.8%	0 0%	0 0%
Pubic Hair (Male): FU-12, Stage 5	25 24.5%	0 0%	0 0%
Pubic Hair (Male): FU-24, Stage 1	1 1%	29 39.7%	14 34.1%
Pubic Hair (Male): FU-24, Stage 2	4 3.9%	2 2.7%	0 0%
Pubic Hair (Male): FU-24, Stage 3	2 2%	1 1.4%	0 0%
Pubic Hair (Male): FU-24, Stage 4	13 12.7%	0 0%	0 0%
Pubic Hair (Male): FU-24, Stage 5	25 24.5%	0 0%	0 0%
Genitalia (Male): Baseline, Stage 1	4 3.9%	31 42.5%	17 41.5%
Genitalia (Male): Baseline, Stage 2	3 2.9%	2 2.7%	0 0%
Genitalia (Male): Baseline, Stage 3	8 7.8%	1 1.4%	0 0%
Genitalia (Male): Baseline, Stage 4	16 15.7%	0 0%	0 0%
Genitalia (Male): Baseline, Stage 5	19 18.6%	0 0%	0 0%
Genitalia (Male): EOT, Stage 1	2 2%	28 38.4%	13 31.7%
Genitalia (Male): EOT, Stage 2	3 2.9%	3 4.1%	0 0%
Genitalia (Male): EOT, Stage 3	7 6.9%	1 1.4%	0 0%
Genitalia (Male): EOT, Stage 4	15 14.7%	0 0%	0 0%
Genitalia (Male): EOT, Stage 5	23 22.5%	0 0%	0 0%
Genitalia (Male): FU-12, Stage 1	1 1%	26 35.6%	14 34.1%
Genitalia (Male): FU-12, Stage 2	4 3.9%	3 4.1%	0 0%
Genitalia (Male): FU-12, Stage 3	7 6.9%	1 1.4%	0 0%
Genitalia (Male): FU-12, Stage 4	11 10.8%	0 0%	0 0%
Genitalia (Male): FU-12, Stage 5	24 23.5%	0 0%	0 0%
Genitalia (Male): FU-24, Stage 1	1 1%	27 37%	14 34.1%
Genitalia (Male): FU-24, Stage 2	2 2%	4 5.5%	0 0%
Genitalia (Male): FU-24, Stage 3	4 3.9%	1 1.4%	0 0%
Genitalia (Male): FU-24, Stage 4	13 12.7%	0 0%	0 0%
Genitalia (Male): FU-24, Stage 5	25 24.5%	0 0%	0 0%
Pubic Hair (Female): Baseline, Stage 1	2 2%	31 42.5%	24 58.5%
Pubic Hair (Female): Baseline, Stage 2	3 2.9%	5 6.8%	0 0%
Pubic Hair (Female): Baseline, Stage 3	9 8.8%	2 2.7%	0 0%
Pubic Hair (Female): Baseline, Stage 4	16 15.7%	0 0%	0 0%
Pubic Hair (Female): Baseline, Stage 5	22 21.6%	0 0%	0 0%
Pubic Hair (Female): EOT, Stage 1	2 2%	29 39.7%	21 51.2%
Pubic Hair (Female): EOT, Stage 2	2 2%	5 6.8%	0 0%
Pubic Hair (Female): EOT, Stage 3	6 5.9%	2 2.7%	0 0%
Pubic Hair (Female): EOT, Stage 4	10 9.8%	1 1.4%	0 0%
Pubic Hair (Female): EOT, Stage 5	30 29.4%	0 0%	0 0%
Pubic Hair (Female): FU-12, Stage 1	2 2%	24 32.9%	21 51.2%
Pubic Hair (Female): FU-12, Stage 2	1 1%	7 9.6%	0 0%
Pubic Hair (Female): FU-12, Stage 3	8 7.8%	3 4.1%	0 0%
Pubic Hair (Female): FU-12, Stage 4	8 7.8%	1 1.4%	0 0%
Pubic Hair (Female): FU-12, Stage 5	32 31.4%	0 0%	0 0%
Pubic Hair (Female): FU-24, Stage 1	2 2%	24 32.9%	20 48.8%
Pubic Hair (Female): FU-24, Stage 2	0 0%	6 8.2%	1 2.4%
Pubic Hair (Female): FU-24, Stage 3	8 7.8%	1 1.4%	0 0%
Pubic Hair (Female): FU-24, Stage 4	9 8.8%	4 5.5%	0 0%
Pubic Hair (Female): FU-24, Stage 5	31 30.4%	0 0%	0 0%
Breasts (Female): Baseline, Stage 1	1 1%	29 39.7%	24 58.5%
Breasts (Female): Baseline, Stage 2	5 4.9%	6 8.2%	0 0%
Breasts (Female): Baseline, Stage 3	6 5.9%	3 4.1%	0 0%
Breasts (Female): Baseline, Stage 4	17 16.7%	0 0%	0 0%
Breasts (Female): Baseline, Stage 5	23 22.5%	0 0%	0 0%
Breasts (Female): EOT, Stage 1	1 1%	25 34.2%	21 51.2%
Breasts (Female): EOT, Stage 2	2 2%	9 12.3%	0 0%
Breasts (Female): EOT, Stage 3	6 5.9%	2 2.7%	0 0%
Breasts (Female): EOT, Stage 4	14 13.7%	1 1.4%	0 0%
Breasts (Female): EOT, Stage 5	27 26.5%	0 0%	0 0%
Breasts (Female): FU-12, Stage 1	1 1%	20 27.4%	21 51.2%
Breasts (Female): FU-12, Stage 2	2 2%	11 15.1%	0 0%
Breasts (Female): FU-12, Stage 3	5 4.9%	2 2.7%	0 0%
Breasts (Female): FU-12, Stage 4	15 14.7%	2 2.7%	0 0%
Breasts (Female): FU-12, Stage 5	28 27.5%	0 0%	0 0%
Breasts (Female): FU-24, Stage 1	1 1%	20 27.4%	20 48.8%
Breasts (Female): FU-24, Stage 2	0 0%	10 13.7%	1 2.4%
Breasts (Female): FU-24, Stage 3	6 5.9%	3 4.1%	0 0%
Breasts (Female): FU-24, Stage 4	13 12.7%	2 2.7%	0 0%
Breasts (Female): FU-24, Stage 5	30 29.4%	0 0%	0 0%

18. Secondary Outcome

Title	Treatment Phase: Growth and Development as Measured by Parental Height
Description	Mid-parental height was calculated as the average of the biological father's and mother's heights. For boys, the sex-adjusted mid-parental height was calculated by adding 2.5 inches or 6.5 cm to the mean of the parents' heights. For girls, 2.5 inches or 6.5 cm was subtracted from the mean of the parents' heights.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	53	39	23
Median (Inter-Quartile Range) [cm]	170.5	170.0	168.7

19. Secondary Outcome

Title	Treatment Phase: Change From Baseline in Growth and Development as Measured by Bone Age
Description	Bone age was determined based on x-ray of the left wrist, hand, and fingers. Baseline value is the last available value on or prior to first dose date of study drug.
Time Frame	Baseline; FU-24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old	3 to < 6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	102	73	41
Baseline	15.5	7.8	4.8
Change From Baseline at FU-24	0.6	1.0	0.5

20. Secondary Outcome

Title	Treatment Phase: Swallowability of SOF/VEL as Assessed by the Participant's Ability to Swallow SOF/VEL Placebo Tablets at Baseline
Description	A SOF/VEL FDC swallowability assessment was performed using placebo tablets at baseline.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed. Swallowability assessment was performed in 12 to <18 years old and 6 to < 12 Years old only.

Arm/Group Title	12 to < 18 Years Old	6 to < 12 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.
Measure Participants	102	73
SOF/VEL 400/100mg Placebo Tablet, Able to Swallow	92 90.2%	1 1.4%
SOF/VEL 400/100mg Placebo, Not Able to Swallow	10 9.8%	0 0%
SOF/VEL 200/50mg Placebo, Able to Swallow	10 9.8%	72 98.6%
SOF/VEL 200/50mg Placebo, Not Able to Swallow	0 0%	1 1.4%

21. Secondary Outcome

Title	Treatment Phase: Number of Participants With Acceptability of SOF/VEL as Measured by a Questionnaire to Assess Acceptability, Including Palatability at Day 1
Description	Acceptability was assessed by numeric response marked on line between numbers 0 - 100. Higher scores indicate better acceptability and/or palatability.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	12 to < 18 Years Old	12 to <18 Years Old	6 to < 12 Years Old	6 to <12 Years Old	3 to < 6 Years Old	3 to <6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: 2 * SOF/VEL 200/50 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg.	SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	91	11	72	1	29	12
Taste, Participants Who Did Not Taste Study Drug	61 59.8%	5 6.8%	42 102.4%	0 0%	8 NaN	5 NaN
Taste, Participants Who Marked > 60 to 100	16 15.7%	3 4.1%	11 26.8%	0 0%	6 NaN	3 NaN
Taste, Participants Who Marked 40 to 60	11 10.8%	1 1.4%	6 14.6%	0 0%	4 NaN	1 NaN
Taste, Participants Who Marked 0 to < 40	3 2.9%	2 2.7%	12 29.3%	1 0.5%	9 NaN	3 NaN
Easy to Take, Participants Who Marked > 60 to 100	82 80.4%	9 12.3%	60 146.3%	0 0%	13 NaN	4 NaN
Easy to Take, Participants Who Marked 40 to 60	5 4.9%	1 1.4%	3 7.3%	0 0%	4 NaN	2 NaN
Easy to Take, Participants Who Marked 0 to < 40	2 2%	1 1.4%	8 19.5%	1 0.5%	10 NaN	6 NaN

22. Secondary Outcome

Title	Treatment Phase: Number of Participants With Acceptability of SOF/VEL as Measured by a Questionnaire to Assess Acceptability, Including Palatability at Week 12
Description	Acceptability was assessed by numeric response marked on line between numbers 0 - 100. Higher scores indicate better acceptability and/or palatability.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	12 to < 18 Years Old	12 to <18 Years Old	6 to < 12 Years Old	6 to <12 Years Old	3 to < 6 Years Old	3 to <6 Years Old
Arm/Group Description	Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: 2 * SOF/VEL 200/50 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg tablets once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks.	Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg.	SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
Measure Participants	91	11	72	1	29	12
Taste, Participants Who Did Not Taste Study Drug	49 48%	2 2.7%	33 80.5%	0 0%	8 NaN	2 NaN
Taste, Participants Who Marked > 60 to 100	24 23.5%	5 6.8%	14 34.1%	0 0%	4 NaN	1 NaN
Taste, Participants Who Marked 40 to 60	10 9.8%	1 1.4%	12 29.3%	1 0.5%	4 NaN	3 NaN
Taste, Participants Who Marked 0 to < 40	7 6.9%	3 4.1%	11 26.8%	0 0%	7 NaN	2 NaN
Easy to Take, Participants Who Marked > 60 to 100	83 81.4%	9 12.3%	65 158.5%	1 0.5%	20 NaN	6 NaN
Easy to Take, Participants Who Marked 40 to 60	3 2.9%	0 0%	5 12.2%	0 0%	1 NaN	1 NaN
Easy to Take, Participants Who Marked 0 to < 40	3 2.9%	2 2.7%	0 0%	0 0%	2 NaN	1 NaN
Feel About Taking Pills, Who Marked > 60 to 100	82 80.4%	8 11%	60 146.3%	NA NaN	NA NaN	NA NaN
Feel About Taking Pills, Who Marked 40 to 60	3 2.9%	1 1.4%	7 17.1%	NA NaN	NA NaN	NA NaN
Feel About Taking Pills, Who Marked 0 to < 40	3 2.9%	2 2.7%	3 7.3%	NA NaN	NA NaN	NA NaN

Adverse Events

Time Frame	Adverse Events: From first dose through last dose of the study drug (Up to 12 weeks) plus 30 days; All-Cause Mortality: First dose date up to Posttreatment Week 24
Adverse Event Reporting Description	The Safety Analysis Set included all participants who were enrolled into the study and received at least 1 dose of study drug (SOF/VEL FDC).
Arm/Group Title	12 to < 18 Years Old		6 to < 12 Years Old		3 to < 6 Years Old
Arm/Group Description	PK Lead-in Phase: Sofosbuvir/Velpatasvir (SOF/VEL) fixed-dose combination (FDC) 400/100 mg tablets once daily for 7 days. Participants who completed the PK lead-in phase, continued into the treatment phase with no interruption of study drug administration and additional participants were enrolled into the treatment phase once the appropriateness of the dose was confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL 400/100 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.		PK Lead-in Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 7 days. Participants who completed the PK lead-in phase, continued into the treatment phase with no interruption of study drug administration and additional participants were enrolled into the treatment phase once the appropriateness of the dose was confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.		PK Lead-in Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 7 days for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 7 days for participants who weighed < 17 kg. Participants who completed the PK lead-in phase, continued into the treatment phase with no interruption of study drug administration and additional participants were enrolled into the treatment phase once the appropriateness of the dose was confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks for participants who weighed ≥ 17 kg. SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.
All Cause Mortality
	12 to < 18 Years Old		6 to < 12 Years Old		3 to < 6 Years Old
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/102 (0%)		0/73 (0%)		0/41 (0%)
Serious Adverse Events
	12 to < 18 Years Old		6 to < 12 Years Old		3 to < 6 Years Old
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/102 (2%)		2/73 (2.7%)		0/41 (0%)
Gastrointestinal disorders
Constipation	0/102 (0%)		1/73 (1.4%)		0/41 (0%)
Psychiatric disorders
Bipolar disorder	1/102 (1%)		0/73 (0%)		0/41 (0%)
Hallucination, auditory	0/102 (0%)		1/73 (1.4%)		0/41 (0%)
Suicidal ideation	2/102 (2%)		0/73 (0%)		0/41 (0%)
Suicide attempt	1/102 (1%)		0/73 (0%)		0/41 (0%)
Other (Not Including Serious) Adverse Events
	12 to < 18 Years Old		6 to < 12 Years Old		3 to < 6 Years Old
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/102 (63.7%)		53/73 (72.6%)		26/41 (63.4%)
Gastrointestinal disorders
Abdominal pain	6/102 (5.9%)		9/73 (12.3%)		2/41 (4.9%)
Abdominal pain upper	10/102 (9.8%)		3/73 (4.1%)		2/41 (4.9%)
Diarrhoea	7/102 (6.9%)		6/73 (8.2%)		5/41 (12.2%)
Nausea	17/102 (16.7%)		5/73 (6.8%)		0/41 (0%)
Vomiting	9/102 (8.8%)		12/73 (16.4%)		11/41 (26.8%)
General disorders
Fatigue	22/102 (21.6%)		9/73 (12.3%)		5/41 (12.2%)
Pyrexia	10/102 (9.8%)		8/73 (11%)		6/41 (14.6%)
Infections and infestations
Nasopharyngitis	6/102 (5.9%)		7/73 (9.6%)		1/41 (2.4%)
Upper respiratory tract infection	3/102 (2.9%)		7/73 (9.6%)		2/41 (4.9%)
Injury, poisoning and procedural complications
Product use issue	0/102 (0%)		2/73 (2.7%)		4/41 (9.8%)
Metabolism and nutrition disorders
Decreased appetite	1/102 (1%)		2/73 (2.7%)		3/41 (7.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/102 (1%)		4/73 (5.5%)		0/41 (0%)
Nervous system disorders
Dizziness	9/102 (8.8%)		2/73 (2.7%)		1/41 (2.4%)
Headache	30/102 (29.4%)		11/73 (15.1%)		2/41 (4.9%)
Respiratory, thoracic and mediastinal disorders
Cough	10/102 (9.8%)		11/73 (15.1%)		6/41 (14.6%)
Epistaxis	3/102 (2.9%)		6/73 (8.2%)		2/41 (4.9%)
Nasal congestion	6/102 (5.9%)		4/73 (5.5%)		5/41 (12.2%)
Oropharyngeal pain	9/102 (8.8%)		2/73 (2.7%)		0/41 (0%)
Rhinorrhoea	4/102 (3.9%)		4/73 (5.5%)		6/41 (14.6%)
Skin and subcutaneous tissue disorders
Rash	0/102 (0%)		7/73 (9.6%)		1/41 (2.4%)

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.