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    Clinical Trial Results:
    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

    Summary
    EudraCT number
    		 2016-002446-23
    Trial protocol
    		 GB   BE   Outside EU/EEA   IT  
    Global end of trial date
    26 Feb 2020

    Results information
    Results version number
    		 v1
    This version publication date
    09 Sep 2020
    First version publication date
    09 Sep 2020
    Other versions
    		 v2

    Trial information

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    Trial identification
    Sponsor protocol code
    GS-US-342-1143
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03022981
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Gilead Sciences
    Sponsor organisation address
    333 Lakeside Drive, Foster City, CA, United States, 94404
    Public contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Scientific contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001646-PIP01-14
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Feb 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    19 Nov 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Feb 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the Pharmacokinetics (PK) Lead-in Phase was 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 was to evaluate the safety and tolerability of SOF/VEL for 12 weeks in pediatric participants with chronic HCV.
    Protection of trial subjects
    The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    26 Jan 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 172
    Country: Number of subjects enrolled
    Italy: 24
    Country: Number of subjects enrolled
    United Kingdom: 15
    Country: Number of subjects enrolled
    Belgium: 5
    Worldwide total number of subjects
    216
    EEA total number of subjects
    44
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    114
    Adolescents (12-17 years)
    102
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    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 final on-study visit occurred on 26 February 2020.

    Pre-assignment
    Screening details
    		 221 participants were screened.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 12 to < 18 Years Old
    Arm description
    		 PK Lead-in Phase: Sofosbuvir/Velpatasvir (SOF/VEL) fixed-dose combination (FDC) 400/100 mg tablets or 2 * 200/50 mg tablets once daily for 7 days. Participants who completed the PK lead-in phase and other additional participants were enrolled into the treatment phase with no interruption of study drug administration until the appropriateness of the dose had been confirmed by PK and safety results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 400/100 mg tablets or 2 * 200/50 mg tablets once daily for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    SOF/VEL FDC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet, Granules
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets or oral granules administered once daily.

    Arm title
    		 6 to < 12 Years Old
    Arm description
    		 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 and other additional participants were enrolled into the treatment phase with no interruption of study drug administration until the appropriateness of the dose had been confirmed by PK and safety results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    SOF/VEL FDC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Granules, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets or oral granules administered once daily.

    Arm title
    		 3 to < 6 Years Old
    Arm description
    		 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 150/37.5 mg FDC oral granules once daily for 7 days for participants who weighed < 17 kg. Participants who completed the PK lead-in phase and other additional participants were enrolled into the treatment phase with no interruption of study drug administration until the appropriateness of the dose had been confirmed by PK and safety 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 150/37.5 mg FDC oral granules once daily for 12 weeks for participants who weighed < 17 kg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    SOF/VEL FDC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Granules, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets or oral granules administered once daily.

    Number of subjects in period 1
    		12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Started
    102
    73
    41
    Completed
    96
    69
    35
    Not completed
    6
    4
    6
         Adverse Event
    -
    1
    -
         Withdrew Assent By Parent/Guardian
    -
    -
    1
         Investigator's Discretion
    -
    1
    2
         Non-Compliance With Study Drug
    -
    -
    2
         Lost to follow-up
    6
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    12 to < 18 Years Old
    Reporting group description
    		 PK Lead-in Phase: Sofosbuvir/Velpatasvir (SOF/VEL) fixed-dose combination (FDC) 400/100 mg tablets or 2 * 200/50 mg tablets once daily for 7 days. Participants who completed the PK lead-in phase and other additional participants were enrolled into the treatment phase with no interruption of study drug administration until the appropriateness of the dose had been confirmed by PK and safety results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 400/100 mg tablets or 2 * 200/50 mg tablets once daily for 12 weeks.

    Reporting group title
    6 to < 12 Years Old
    Reporting group description
    		 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 and other additional participants were enrolled into the treatment phase with no interruption of study drug administration until the appropriateness of the dose had been confirmed by PK and safety results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.

    Reporting group title
    3 to < 6 Years Old
    Reporting group description
    		 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 150/37.5 mg FDC oral granules once daily for 7 days for participants who weighed < 17 kg. Participants who completed the PK lead-in phase and other additional participants were enrolled into the treatment phase with no interruption of study drug administration until the appropriateness of the dose had been confirmed by PK and safety 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 150/37.5 mg FDC oral granules once daily for 12 weeks for participants who weighed < 17 kg.

    Reporting group values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old Total
    Number of subjects
    		 102 73 41 216
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 15 ( 1.9 ) 8 ( 1.6 ) 4 ( 0.8 ) -
    Gender categorical
    Units: Subjects
        Female
    		 52 38 24 114
        Male
    		 50 35 17 102
    Race
    Here, Not Permitted = local requirements did not permit collection of race or ethnicity information.
    Units: Subjects
        White
    		 74 66 32 172
        Black or African American
    		 9 4 3 16
        Asian
    		 11 1 0 12
        Other
    		 5 2 5 12
        American Indian or Alaska Native
    		 2 0 0 2
        Not Permitted
    		 1 0 1 2
        Native Hawaiian or Pacific Islander
    		 0 0 0 0
    Ethnicity
    Here, Not Permitted = local requirements did not permit collection of race or ethnicity information.
    Units: Subjects
        Hispanic or Latino
    		 14 7 4 25
        Not Hispanic or Latino
    		 83 64 36 183
        Not Permitted
    		 5 2 1 8

    End points

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    End points reporting groups
    Reporting group title
    12 to < 18 Years Old
    Reporting group description
    		 PK Lead-in Phase: Sofosbuvir/Velpatasvir (SOF/VEL) fixed-dose combination (FDC) 400/100 mg tablets or 2 * 200/50 mg tablets once daily for 7 days. Participants who completed the PK lead-in phase and other additional participants were enrolled into the treatment phase with no interruption of study drug administration until the appropriateness of the dose had been confirmed by PK and safety results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 400/100 mg tablets or 2 * 200/50 mg tablets once daily for 12 weeks.

    Reporting group title
    6 to < 12 Years Old
    Reporting group description
    		 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 and other additional participants were enrolled into the treatment phase with no interruption of study drug administration until the appropriateness of the dose had been confirmed by PK and safety results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 200/50 mg tablets or oral granules once daily for 12 weeks.

    Reporting group title
    3 to < 6 Years Old
    Reporting group description
    		 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 150/37.5 mg FDC oral granules once daily for 7 days for participants who weighed < 17 kg. Participants who completed the PK lead-in phase and other additional participants were enrolled into the treatment phase with no interruption of study drug administration until the appropriateness of the dose had been confirmed by PK and safety 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 150/37.5 mg FDC oral granules once daily for 12 weeks for participants who weighed < 17 kg.

    Subject analysis set title
    12 to <18 Years Old
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Treatment Phase: 2 * SOF/VEL 200/50 mg (adult and smaller size tablets based on swallowability assessment) once daily for 12 weeks.

    Subject analysis set title
    6 to <12 Years Old
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Treatment Phase: SOF/VEL FDC 200/50 mg oral granules once daily for 12 weeks.

    Subject analysis set title
    3 to <6 Years Old
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    SOF/VEL FDC 150/37.5 mg oral granules once daily for 12 weeks for participants who weighed < 17 kg.

    Primary: PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Velpatasvir (VEL)

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    End point title
    		 PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Velpatasvir (VEL) [1]
    End point description
    AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval). 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.
    End point type
    Primary
    End point timeframe
    Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical comparison was planned or performed.
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    16
    17
    18
    Units: hours*nanograms per millilitre (h*ng/mL)
        arithmetic mean (standard deviation)
    4479.3 ( 2105.66 )
    3697.5 ( 1653.25 )
    4450.3 ( 3285.75 )
    No statistical analyses for this end point

    Primary: PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Sofosbuvir (SOF)

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    End point title
    		 PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Sofosbuvir (SOF) [2]
    End point description
    AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval). Participants in the Lead-in Phase PK Analysis Set with available data were analyzed.
    End point type
    Primary
    End point timeframe
    Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical comparison was planned or performed.
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    16
    17
    17
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    3020.1 ( 1162.56 )
    1764.5 ( 690.12 )
    3306.2 ( 3499.49 )
    No statistical analyses for this end point

    Primary: PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of GS-331007 (Metabolite of SOF)

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    End point title
    		 PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of GS-331007 (Metabolite of SOF) [3]
    End point description
    AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval). Participants in the Lead-in Phase PK Analysis Set with available data were analyzed.
    End point type
    Primary
    End point timeframe
    Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical comparison was planned or performed.
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    16
    17
    18
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    13852.9 ( 3565.85 )
    9913.8 ( 3071.79 )
    11604.0 ( 2732.57 )
    No statistical analyses for this end point

    Primary: Treatment Phase: Percentage of Participants Who Discontinued Study Drug Due to Any Treatment-Emergent Adverse Event (TEAE)

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    End point title
    		 Treatment Phase: Percentage of Participants Who Discontinued Study Drug Due to Any Treatment-Emergent Adverse Event (TEAE) [4]
    End point 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. 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).
    End point type
    Primary
    End point timeframe
    From first dose through last dose of the study drug (Up to 12 weeks) plus 30 days
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical comparison was planned or performed.
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    102
    73
    41
    Units: percentage of participants
        number (not applicable)
    0.0
    2.7
    2.4
    No statistical analyses for this end point

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

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    End point title
    		 PK Lead-in Phase: Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 7
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline; Day 7
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    17
    20
    19
    Units: log10 international units (IU)/mL
    arithmetic mean (standard deviation)
        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 )
    No statistical analyses for this end point

    Secondary: PK Lead-in Phase: Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse (AE)

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    End point title
    		 PK Lead-in Phase: Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse (AE)
    End point 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. Participants in the Lead-in Phase PK Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First dose date up to Day 7
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    17
    20
    19
    Units: percentage of participants
        number (not applicable)
    0.0
    0.0
    0.0
    No statistical analyses for this end point

    Secondary: Treatment Phase: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)

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    End point title
    		 Treatment Phase: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)
    End point description
    SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment. 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).
    End point type
    Secondary
    End point timeframe
    Posttreatment Week 12
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    102
    73
    41
    Units: percentage of participants
        number (confidence interval 95%)
    95.1 (88.9 to 98.4)
    93.2 (84.7 to 97.7)
    82.9 (67.9 to 92.8)
    No statistical analyses for this end point

    Secondary: Treatment Phase: Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)

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    End point title
    		 Treatment Phase: Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
    End point description
    SVR4 was defined as HCV RNA < LLOQ (ie, 15 IU/mL) at 4 weeks after stopping study treatment. Participants in the Full Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Posttreatment Week 4
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    102
    73
    41
    Units: percentage of participants
        number (confidence interval 95%)
    96.1 (90.3 to 98.9)
    94.5 (86.6 to 98.5)
    82.9 (67.9 to 92.8)
    No statistical analyses for this end point

    Secondary: Treatment Phase: Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)

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    End point title
    		 Treatment Phase: Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)
    End point description
    SVR 24 was defined as HCV RNA < LLOQ (ie, 15 IU/mL) at 24 weeks after stopping study treatment. Participants in the Full Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Posttreatment Week 24
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    102
    73
    41
    Units: percentage of participants
        number (confidence interval 95%)
    95.1 (88.9 to 98.4)
    93.2 (84.7 to 97.7)
    82.9 (67.9 to 92.8)
    No statistical analyses for this end point

    Secondary: Treatment Phase: Percentage of Participants With Virologic Failure

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    End point title
    		 Treatment Phase: Percentage of Participants With Virologic Failure
    End point 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. Participants in the Full Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Up to Posttreatment Week 24
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    102
    73
    41
    Units: percentage of participants
        number (not applicable)
    1.0
    1.4
    0.0
    No statistical analyses for this end point

    Secondary: Treatment Phase: Percentage of Participants With HCV RNA < LLOQ On Treatment

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    End point title
    		 Treatment Phase: Percentage of Participants With HCV RNA < LLOQ On Treatment
    End point description
    Percentage of participants with HCV RNA < LLOQ while on treatment by analysis visit. Participants in the Full Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 4, 8, and 12
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    102
    73
    41
    Units: percentage of participants
    number (confidence interval 95%)
        Week 1
    44.1 (34.3 to 54.3)
    39.7 (28.5 to 51.9)
    36.8 (21.8 to 54.0)
        Week 4
    96.1 (90.3 to 98.9)
    94.4 (86.2 to 98.4)
    91.4 (76.9 to 98.2)
        Week 8
    100.0 (96.4 to 100.0)
    98.6 (92.3 to 100.0)
    100.0 (89.7 to 100.0)
        Week 12
    100.0 (96.4 to 100.0)
    98.6 (92.3 to 100.0)
    100.0 (89.7 to 100.0)
    No statistical analyses for this end point

    Secondary: Treatment Phase: Percentage of Participants Who Develop Viral Resistance to SOF and/or VEL During Treatment and After Discontinuation of Treatment

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    End point title
    		 Treatment Phase: Percentage of Participants Who Develop Viral Resistance to SOF and/or VEL During Treatment and After Discontinuation of Treatment
    End point 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).
    End point type
    Secondary
    End point timeframe
    First dose date up to Posttreatment Week 24
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    98
    68
    33
    Units: percentage of participants
    number (not applicable)
        Pretreatment NS5A NI RAVs
    16.3
    10.2
    18.1
        Pretreatment NS5B NI RAVs
    5.1
    0.0
    3.0
    No statistical analyses for this end point

    Secondary: Treatment Phase: Change From Baseline in HCV RNA at Weeks 1, 4, 8, and 12

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    End point title
    		 Treatment Phase: Change From Baseline in HCV RNA at Weeks 1, 4, 8, and 12
    End point description
    Participants in the Full Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline; Weeks 1, 4, 8, and 12
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    102
    73
    41
    Units: log10 IU/mL
    arithmetic mean (standard deviation)
        Baseline
    6.06 ( 0.585 )
    5.87 ( 0.686 )
    5.86 ( 1.057 )
        Change from Baseline at Week 1 (N = 102, 71, 36)
    -4.46 ( 0.661 )
    -4.28 ( 0.632 )
    -4.06 ( 0.914 )
        Change from Baseline at Week 4 (N = 102, 71, 34)
    -4.89 ( 0.578 )
    -4.64 ( 0.860 )
    -4.49 ( 1.040 )
        Change from Baseline at Week 8 (N = 101, 70, 34)
    -4.91 ( 0.588 )
    -4.69 ( 0.678 )
    -4.56 ( 1.066 )
        Change from Baseline at Week 12 (N = 101, 69, 34)
    -4.91 ( 0.588 )
    -4.70 ( 0.683 )
    -4.56 ( 1.066 )
    No statistical analyses for this end point

    Secondary: Treatment Phase: Quality of Life (QoL) and Neuropsychiatric Assessments as Measured by PedsQL™ Pediatric QoL Survey

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    End point title
    		 Treatment Phase: Quality of Life (QoL) and Neuropsychiatric Assessments as Measured by PedsQL™ Pediatric QoL Survey
    End point 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 (baseline/BL), end of treatment (EOT), early termination (if applicable), and posttreatment Weeks (Wk) 12 (follow up-12/FU-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. Participants in the Full Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 12, End of Treatment (EOT), Posttreatment/Follow-up (FU) Week-12 (FU-12), and FU Week-24 (FU-24)
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    102
    73
    41
    Units: score on a scale
    arithmetic mean (standard deviation)
        Parent Reports, Total Score at BL (N=98,73,41)
    80.0 ( 17.71 )
    79.7 ( 15.58 )
    86.5 ( 12.43 )
        Parent Reports, Total Score at Wk 12(N=97,68,32)
    82.4 ( 18.13 )
    82.8 ( 14.26 )
    87.3 ( 11.31 )
        Parent Reports, Total Score at EOT (N=97,70,34)
    82.4 ( 18.13 )
    82.2 ( 14.95 )
    87.0 ( 11.65 )
        Parent Reports, Total Score at FU-12 (N=94,68,35)
    81.7 ( 17.39 )
    81.5 ( 15.34 )
    87.7 ( 14.11 )
        Parent Reports, Total Score at FU-24 (N=94,69,35)
    80.8 ( 18.65 )
    79.7 ( 15.30 )
    88.3 ( 9.79 )
        Part. Reports,Total Score at BL(N=100,73,18)
    79.9 ( 15.22 )
    77.9 ( 13.33 )
    82.2 ( 12.47 )
        Part. Reports,Total Score at Wk 12(N=101,68,21)
    80.9 ( 16.38 )
    80.0 ( 14.21 )
    83.3 ( 11.62 )
        Part. Reports,Total Score at EOT(N=101,70,21)
    80.9 ( 16.38 )
    79.7 ( 14.13 )
    83.3 ( 11.62 )
        Part. Reports,Total Score at FU-12(N=98,68,23)
    82.5 ( 15.41 )
    81.1 ( 13.32 )
    80.5 ( 14.18 )
        Part. Reports,Total Score at FU-24(N=98,69,25)
    81.4 ( 16.34 )
    81.7 ( 15.43 )
    82.1 ( 12.56 )
    No statistical analyses for this end point

    Secondary: Treatment Phase: Change From Baseline in Growth and Development as Measured by Height Percentiles

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    End point title
    		 Treatment Phase: Change From Baseline in Growth and Development as Measured by Height Percentiles
    End point 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. Participants in the Safety Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline; Weeks 1, 4, 8, 12, Follow-up (FU) Week 4 (FU-4), FU-12, and FU-24
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    102
    73
    41
    Units: cm
    median (inter-quartile range (Q1-Q3))
        Baseline
    44.5 (16.2 to 74.1)
    41.9 (20.5 to 65.2)
    39.3 (13.9 to 70.1)
        Change from Baseline at Week 1 (N = 102, 73, 36)
    0.0 (-0.4 to 0.9)
    0.1 (-0.7 to 2.4)
    0.5 (-1.1 to 3.4)
        Change from Baseline at Week 4 (N = 101, 71, 34)
    0.0 (-0.7 to 1.7)
    0.2 (-1.9 to 1.9)
    1.4 (-0.3 to 3.7)
        Change from Baseline at Week 8 (N = 101, 69, 34)
    0.0 (-1.2 to 1.5)
    -0.1 (-2.2 to 2.2)
    0.3 (-2.1 to 3.6)
        Change from Baseline at Week 12 (N = 100, 65, 28)
    -0.1 (-1.4 to 1.0)
    0.2 (-2.6 to 2.8)
    0.2 (-2.0 to 5.1)
        Change from Baseline at FU-4 (N = 99, 70, 34)
    0.0 (-2.0 to 1.3)
    0.2 (-2.3 to 2.5)
    1.2 (-0.7 to 5.6)
        Change from Baseline at FU-12 (N = 98, 68, 35)
    -0.2 (-2.4 to 1.4)
    0.1 (-1.7 to 2.6)
    0.6 (-3.1 to 4.6)
        Change from Baseline at FU-24 (N = 91, 67, 33)
    -0.6 (-2.6 to 1.9)
    -0.2 (-3.1 to 3.5)
    0.3 (-2.1 to 6.0)
    No statistical analyses for this end point

    Secondary: Treatment Phase: Change From Baseline in Growth and Development as Measured by Weight Percentiles

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    End point title
    		 Treatment Phase: Change From Baseline in Growth and Development as Measured by Weight Percentiles
    End point 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. Participants in the Safety Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline; Weeks 1, 4, 8, 12, FU-4, FU-12, and FU-24
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    102
    73
    41
    Units: kg
    median (inter-quartile range (Q1-Q3))
        Baseline
    67.2 (31.5 to 84.1)
    45.9 (23.3 to 78.6)
    64.6 (38.0 to 86.7)
        Change from Baseline at Week 1 (N = 102, 73, 36)
    0.0 (-0.4 to 0.9)
    0.1 (-0.6 to 1.2)
    -0.5 (-2.7 to 0.7)
        Change from Baseline at Week 4 (N = 102, 71, 34)
    0.0 (-0.9 to 1.8)
    0.2 (-1.4 to 1.5)
    0.3 (-1.2 to 2.0)
        Change from Baseline at Week 8 (N = 101, 69, 34)
    0.0 (-1.3 to 2.1)
    0.1 (-1.6 to 2.5)
    0.2 (-3.7 to 2.5)
        Change from Baseline at Week 12 (N = 100, 65, 28)
    0.2 (-1.0 to 2.9)
    0.5 (-1.7 to 2.5)
    -1.7 (-4.7 to 0.6)
        Change from Baseline at FU-4 (N = 99, 70, 34)
    0.1 (-3.0 to 3.1)
    0.0 (-2.3 to 2.6)
    -0.8 (-4.9 to 2.4)
        Change from Baseline at FU-12 (N = 98, 68, 35)
    0.0 (-2.5 to 4.7)
    0.5 (-2.2 to 4.9)
    -0.8 (-6.6 to 2.2)
        Change from Baseline at FU-24 (N = 91, 67, 33)
    0.1 (-2.6 to 4.1)
    1.4 (-1.2 to 5.7)
    -1.3 (-3.5 to 2.9)
    No statistical analyses for this end point

    Secondary: Treatment Phase: Changes in Growth and Development as Measured by Tanner Stage Assessment From Baseline

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    End point title
    		 Treatment Phase: Changes in Growth and Development as Measured by Tanner Stage Assessment From Baseline
    End point 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). Safety Analysis Set.
    End point type
    Secondary
    End point timeframe
    Up to Posttreatment Week 24
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    102
    73
    41
    Units: participants
        Pubic Hair (Male): Baseline, Stage 1 (N=50,35,17)
    4
    31
    17
        Pubic Hair (Male): Baseline, Stage 2 (N=50,35,17)
    3
    2
    0
        Pubic Hair (Male): Baseline, Stage 3 (N=50,35,17)
    10
    1
    0
        Pubic Hair (Male): Baseline, Stage 4 (N=50,35,17)
    14
    0
    0
        Pubic Hair (Male): Baseline, Stage 5 (N=50,35,17)
    19
    0
    0
        Pubic Hair (Male): EOT, Stage 1 (N=50,32,13)
    2
    28
    13
        Pubic Hair (Male): EOT, Stage 2 (N=50,32,13)
    4
    3
    0
        Pubic Hair (Male): EOT, Stage 3 (N=50,32,13)
    7
    1
    0
        Pubic Hair (Male): EOT, Stage 4 (N=50,32,13)
    13
    0
    0
        Pubic Hair (Male): EOT, Stage 5 (N=50,32,13)
    24
    0
    0
        Pubic Hair (Male): FU-12, Stage 1 (N=47,30,14)
    1
    27
    14
        Pubic Hair (Male): FU-12, Stage 2 (N=47,30,14)
    5
    3
    0
        Pubic Hair (Male): FU-12, Stage 3 (N=47,30,14)
    6
    1
    0
        Pubic Hair (Male): FU-12, Stage 4 (N=47,30,14)
    10
    0
    0
        Pubic Hair (Male): FU-12, Stage 5 (N=47,30,14)
    25
    0
    0
        Pubic Hair (Male): FU-24, Stage 1 (N=45,32,14)
    1
    30
    14
        Pubic Hair (Male): FU-24, Stage 2 (N=45,32,14)
    4
    2
    0
        Pubic Hair (Male): FU-24, Stage 3 (N=45,32,14)
    2
    1
    0
        Pubic Hair (Male): FU-24, Stage 4 (N=45,32,14)
    13
    0
    0
        Pubic Hair (Male): FU-24, Stage 5 (N=45,32,14)
    25
    0
    0
        Genitalia (Male): Baseline, Stage 1 (N=50,35,17)
    4
    31
    17
        Genitalia (Male): Baseline, Stage 2 (N=50,35,17)
    3
    2
    0
        Genitalia (Male): Baseline, Stage 3 (N=50,35,17)
    8
    1
    0
        Genitalia (Male): Baseline, Stage 4 (N=50,35,17)
    16
    0
    0
        Genitalia (Male): Baseline, Stage 5 (N=50,35,17)
    19
    0
    0
        Genitalia (Male): EOT, Stage 1 (N=50,32,13)
    2
    28
    13
        Genitalia (Male): EOT, Stage 2 (N=50,32,13)
    3
    3
    0
        Genitalia (Male): EOT, Stage 3 (N=50,32,13)
    7
    1
    0
        Genitalia (Male): EOT, Stage 4 (N=50,32,13)
    15
    0
    0
        Genitalia (Male): EOT, Stage 5 (N=50,32,13)
    23
    0
    0
        Genitalia (Male): FU-12, Stage 1 (N=47,30,14)
    1
    27
    14
        Genitalia (Male): FU-12, Stage 2 (N=47,30,14)
    4
    3
    0
        Genitalia (Male): FU-12, Stage 3 (N=47,30,14)
    7
    1
    0
        Genitalia (Male): FU-12, Stage 4 (N=47,30,14)
    11
    0
    0
        Genitalia (Male): FU-12, Stage 5 (N=47,30,14)
    24
    0
    0
        Genitalia (Male): FU-24, Stage 1 (N=45,32,14)
    1
    28
    14
        Genitalia (Male): FU-24, Stage 2 (N=45,32,14)
    2
    4
    0
        Genitalia (Male): FU-24, Stage 3 (N=45,32,14)
    4
    1
    0
        Genitalia (Male): FU-24, Stage 4 (N=45,32,14)
    13
    0
    0
        Genitalia (Male): FU-24, Stage 5 (N=45,32,14)
    25
    0
    0
        Pubic Hair (Female): Baseline, Stage 1(N=52,38,24)
    2
    31
    24
        Pubic Hair (Female): Baseline, Stage 2(N=52,38,24)
    3
    5
    0
        Pubic Hair (Female): Baseline, Stage 3(N=52,38,24)
    9
    2
    0
        Pubic Hair (Female): Baseline, Stage 4(N=52,38,24)
    16
    0
    0
        Pubic Hair (Female): Baseline, Stage 5(N=52,38,24)
    22
    0
    0
        Pubic Hair (Female): EOT, Stage 1 (N=50,37,21)
    2
    29
    21
        Pubic Hair (Female): EOT, Stage 2 (N=50,37,21)
    2
    5
    0
        Pubic Hair (Female): EOT, Stage 3 (N=50,37,21)
    6
    2
    0
        Pubic Hair (Female): EOT, Stage 4 (N=50,37,21)
    10
    1
    0
        Pubic Hair (Female): EOT, Stage 5 (N=50,37,21)
    30
    0
    0
        Pubic Hair (Female): FU-12, Stage 1 (N=51,35,21)
    2
    24
    21
        Pubic Hair (Female): FU-12, Stage 2 (N=51,35,21)
    1
    7
    0
        Pubic Hair (Female): FU-12, Stage 3 (N=51,35,21)
    8
    3
    0
        Pubic Hair (Female): FU-12, Stage 4 (N=51,35,21)
    8
    1
    0
        Pubic Hair (Female): FU-12, Stage 5 (N=51,35,21)
    32
    0
    0
        Pubic Hair (Female): FU-24, Stage 1 (N=50,35,21)
    2
    24
    20
        Pubic Hair (Female): FU-24, Stage 2 (N=50,35,21)
    0
    6
    1
        Pubic Hair (Female): FU-24, Stage 3 (N=50,35,21)
    8
    1
    0
        Pubic Hair (Female): FU-24, Stage 4 (N=50,35,21)
    9
    4
    0
        Pubic Hair (Female): FU-24, Stage 5 (N=50,35,21)
    31
    0
    0
        Breasts (Female): Baseline, Stage 1 (N=52,38,24)
    1
    29
    24
        Breasts (Female): Baseline, Stage 2 (N=52,38,24)
    5
    6
    0
        Breasts (Female): Baseline, Stage 3 (N=52,38,24)
    6
    3
    0
        Breasts (Female): Baseline, Stage 4 (N=52,38,24)
    17
    0
    0
        Breasts (Female): Baseline, Stage 5 (N=52,38,24)
    23
    0
    0
        Breasts (Female): EOT, Stage 1 (N=50,37,21)
    1
    25
    21
        Breasts (Female): EOT, Stage 2 (N=50,37,21)
    2
    9
    0
        Breasts (Female): EOT, Stage 3 (N=50,37,21)
    6
    2
    0
        Breasts (Female): EOT, Stage 4 (N=50,37,21)
    14
    1
    0
        Breasts (Female): EOT, Stage 5 (N=50,37,21)
    27
    0
    0
        Breasts (Female): FU-12, Stage 1 (N=51,35,21)
    1
    20
    21
        Breasts (Female): FU-12, Stage 2 (N=51,35,21)
    2
    11
    0
        Breasts (Female): FU-12, Stage 3 (N=51,35,21)
    5
    2
    0
        Breasts (Female): FU-12, Stage 4 (N=51,35,21)
    15
    2
    0
        Breasts (Female): FU-12, Stage 5 (N=51,35,21)
    28
    0
    0
        Breasts (Female): FU-24, Stage 1 (N=50,35,21)
    1
    20
    20
        Breasts (Female): FU-24, Stage 2 (N=50,35,21)
    0
    10
    1
        Breasts (Female): FU-24, Stage 3 (N=50,35,21)
    6
    3
    0
        Breasts (Female): FU-24, Stage 4 (N=50,35,21)
    13
    2
    0
        Breasts (Female): FU-24, Stage 5 (N=50,35,21)
    30
    0
    0
    No statistical analyses for this end point

    Secondary: Growth and Development as Measured by Parental Height

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    End point title
    		 Growth and Development as Measured by Parental Height
    End point 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. Participants in the Safety Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    53
    39
    23
    Units: cm
        median (inter-quartile range (Q1-Q3))
    170.5 (162.0 to 176.7)
    170.0 (163.7 to 178.6)
    168.7 (163.0 to 174.1)
    No statistical analyses for this end point

    Secondary: Treatment Phase: Change From Baseline in Growth and Development as Measured by Bone Age

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    End point title
    		 Treatment Phase: Change From Baseline in Growth and Development as Measured by Bone Age
    End point 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. Participants in the Full Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline; FU-24
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Number of subjects analysed
    102
    73
    41
    Units: years
    median (inter-quartile range (Q1-Q3))
        Baseline (N = 102, 72, 40)
    15.5 (13.5 to 17.0)
    7.8 (6.8 to 9.0)
    4.8 (4.2 to 5.5)
        Change from Baseline at FU-24 (N = 92, 68, 35)
    0.6 (0.0 to 1.0)
    1.0 (0.0 to 1.2)
    0.5 (0.0 to 1.1)
    No statistical analyses for this end point

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

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    End point title
    		 Treatment Phase: Swallowability of SOF/VEL as Assessed by the Participant's Ability to Swallow SOF/VEL Placebo Tablets at Baseline [5]
    End point description
    A SOF/VEL FDC swallowability assessment was performed using placebo (PBO) tablets at baseline. 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.
    End point type
    Secondary
    End point timeframe
    Baseline
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical comparison was planned or performed.
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old
    Number of subjects analysed
    102
    73
    Units: participants
        SOF/VEL 400/100mg PBO,Able to Swallow(N=102,1)
    92
    1
        SOF/VEL 400/100mg PBO,Not Able to Swallow(N=102,1)
    10
    0
        SOF/VEL 200/50mg PBO,Able to Swallow(N=10,73)
    10
    72
        SOF/VEL 200/50mg PBO,Not Able to Swallow(N=10,73)
    0
    1
    No statistical analyses for this end point

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

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    End point title
    		 Treatment Phase: Number of Participants With Acceptability of SOF/VEL as Measured by a Questionnaire to Assess Acceptability, Including Palatability at Day 1
    End point description
    Acceptability was assessed by numeric response marked on line between numbers 0 - 100. Higher scores indicate better acceptability and/or palatability. Participants in the Full Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old 12 to <18 Years Old 6 to <12 Years Old 3 to <6 Years Old
    Number of subjects analysed
    91
    72
    29
    11
    1
    12
    Units: participants
        Taste, Participants Who Did Not Taste Study Drug
    61
    42
    8
    5
    0
    5
        Taste, Participants Who Marked > 60 to 100
    16
    11
    6
    3
    0
    3
        Taste, Participants Who Marked 40 to 60
    11
    6
    4
    1
    0
    1
        Taste, Participants Who Marked 0 to < 40
    3
    12
    9
    2
    1
    3
        Easy to Take, Who Marked > 60 to 100 (N=89,71,27)
    82
    60
    13
    9
    0
    4
        Easy to Take, Who Marked 40 to 60 (N=89,71,27)
    5
    3
    4
    1
    0
    2
        Easy to Take, Who Marked 0 to < 40 (N=89,71,27)
    2
    8
    10
    1
    1
    6
    No statistical analyses for this end point

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

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    End point title
    		 Treatment Phase: Number of Participants With Acceptability of SOF/VEL as Measured by a Questionnaire to Assess Acceptability, Including Palatability at Week 12
    End point description
    Acceptability was assessed by numeric response marked on line between numbers 0 - 100. Higher scores indicate better acceptability and/or palatability. Participants in the Full Analysis Set with available data were analyzed. Here, 99999 = Data not applicable for the oral granules group.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old 12 to <18 Years Old 6 to <12 Years Old 3 to <6 Years Old
    Number of subjects analysed
    91
    72
    29
    11
    1
    12
    Units: participants
        Taste, Who Did Not Taste Study Drug(N=90,70,23)
    49
    33
    8
    2
    0
    2
        Taste, Who Marked > 60 to 100 (N=90,70,23)
    24
    14
    4
    5
    0
    1
        Taste, Who Marked 40 to 60 (N=90,70,23)
    10
    12
    4
    1
    1
    3
        Taste, Who Marked 0 to < 40 (N=90,70,23)
    7
    11
    7
    3
    0
    2
        Easy to Take, Who Marked > 60 to 100 (N=89,70,23)
    83
    65
    20
    9
    1
    6
        Easy to Take, Who Marked 40 to 60 (N=89,70,23)
    3
    5
    1
    0
    0
    1
        Easy to Take, Who Marked 0 to < 40 (N=89,70,23)
    3
    0
    2
    2
    0
    1
        Feels Taking Pills, > 60 to 100 mark (N=88,70,23)
    82
    60
    99999
    8
    99999
    99999
        Feels Taking Pills, 40 to 60 mark (N=88,70,23)
    3
    7
    99999
    1
    99999
    99999
        Feels Taking Pills, 0 to < 40 mark (N=88,70,23)
    3
    3
    99999
    2
    99999
    99999
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    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 additional 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).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    12 to < 18 Years Old
    Reporting group description
    		 PK Lead-in Phase: Sofosbuvir/Velpatasvir (SOF/VEL) fixed-dose combination (FDC) 400/100 mg tablets or oral granules once daily for 7 days. Participants who completed the PK lead-in phase and other additional participants were enrolled into the treatment phase with no interruption of study drug administration until the appropriateness of the dose had been confirmed by PK and safety results from the PK lead-in phase. Treatment Phase: SOF/VEL FDC 400/100 mg tablets or oral granules once daily for 12 weeks.

    Reporting group title
    6 to < 12 Years Old
    Reporting group description
    		 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.

    Reporting group title
    3 to < 6 Years Old
    Reporting group description
    		 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.

    Serious adverse events
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 102 (1.96%)
    2 / 73 (2.74%)
    0 / 41 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 73 (1.37%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicidal ideation
         subjects affected / exposed
    2 / 102 (1.96%)
    0 / 73 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bipolar disorder
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 73 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hallucination, auditory
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 73 (1.37%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 73 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 12 to < 18 Years Old 6 to < 12 Years Old 3 to < 6 Years Old
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    65 / 102 (63.73%)
    53 / 73 (72.60%)
    26 / 41 (63.41%)
    Injury, poisoning and procedural complications
    Product use issue
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 73 (2.74%)
    4 / 41 (9.76%)
         occurrences all number
    0
    3
    4
    Nervous system disorders
    Headache
         subjects affected / exposed
    30 / 102 (29.41%)
    11 / 73 (15.07%)
    2 / 41 (4.88%)
         occurrences all number
    49
    17
    2
    Dizziness
         subjects affected / exposed
    9 / 102 (8.82%)
    2 / 73 (2.74%)
    1 / 41 (2.44%)
         occurrences all number
    11
    3
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    22 / 102 (21.57%)
    9 / 73 (12.33%)
    5 / 41 (12.20%)
         occurrences all number
    25
    9
    6
    Pyrexia
         subjects affected / exposed
    10 / 102 (9.80%)
    8 / 73 (10.96%)
    6 / 41 (14.63%)
         occurrences all number
    10
    9
    8
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    9 / 102 (8.82%)
    12 / 73 (16.44%)
    11 / 41 (26.83%)
         occurrences all number
    11
    13
    15
    Nausea
         subjects affected / exposed
    17 / 102 (16.67%)
    5 / 73 (6.85%)
    0 / 41 (0.00%)
         occurrences all number
    18
    5
    0
    Diarrhoea
         subjects affected / exposed
    7 / 102 (6.86%)
    6 / 73 (8.22%)
    5 / 41 (12.20%)
         occurrences all number
    7
    7
    6
    Abdominal pain
         subjects affected / exposed
    6 / 102 (5.88%)
    9 / 73 (12.33%)
    2 / 41 (4.88%)
         occurrences all number
    7
    11
    4
    Abdominal pain upper
         subjects affected / exposed
    10 / 102 (9.80%)
    3 / 73 (4.11%)
    2 / 41 (4.88%)
         occurrences all number
    11
    5
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    10 / 102 (9.80%)
    11 / 73 (15.07%)
    6 / 41 (14.63%)
         occurrences all number
    10
    15
    8
    Nasal congestion
         subjects affected / exposed
    6 / 102 (5.88%)
    4 / 73 (5.48%)
    5 / 41 (12.20%)
         occurrences all number
    8
    5
    5
    Rhinorrhoea
         subjects affected / exposed
    4 / 102 (3.92%)
    4 / 73 (5.48%)
    6 / 41 (14.63%)
         occurrences all number
    4
    4
    7
    Epistaxis
         subjects affected / exposed
    3 / 102 (2.94%)
    6 / 73 (8.22%)
    2 / 41 (4.88%)
         occurrences all number
    3
    9
    2
    Oropharyngeal pain
         subjects affected / exposed
    9 / 102 (8.82%)
    2 / 73 (2.74%)
    0 / 41 (0.00%)
         occurrences all number
    9
    2
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 102 (0.00%)
    7 / 73 (9.59%)
    1 / 41 (2.44%)
         occurrences all number
    0
    7
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 102 (0.98%)
    4 / 73 (5.48%)
    0 / 41 (0.00%)
         occurrences all number
    1
    4
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    6 / 102 (5.88%)
    7 / 73 (9.59%)
    1 / 41 (2.44%)
         occurrences all number
    7
    7
    1
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 102 (2.94%)
    7 / 73 (9.59%)
    2 / 41 (4.88%)
         occurrences all number
    3
    8
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 102 (0.98%)
    2 / 73 (2.74%)
    3 / 41 (7.32%)
         occurrences all number
    1
    2
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Sep 2016
    • Added clarification that all adverse events (AEs) were recorded with a focus on those AEs leading to study drug discontinuation for evaluation of the primary safety endpoint • Updated the SOF/VEL stopping criteria to align with the LDV/SOF and SOF laboratory stopping criteria in adult and pediatric clinical studies • Added eligibility criteria pertaining to liver enzymes and bilirubin to align with the exclusion criteria parameters in SOF/VEL adult clinical studies • Clarified that only the subject was required to complete the acceptability questionnaire at Day 1, but it may be completed by the parent or legal guardian if the subject is unable to read • Clarified that the Day 3 study visit was performed over the phone and the site assessed the subject’s dosing compliance by reviewing the dosing diary remotely with the subject, parent, or legal guardian • Added SOF/VEL Acceptability Questionnaire assessment to the early termination visit • Appendix 3 (Management of Clinical and Laboratory AEs) was removed due to a discrepancy in the protocol stopping rules within the protocol
    01 Dec 2016
    • Added serial hepatitis B virus (HBV) DNA monitoring for any subject with hepatitis B core antibody (HBcAb)-positive status at screening, per a US Food and Drug Administration Drug Safety Communication • Added formulation, packaging, labeling, storage, and handling information for the SOF/VEL 200/50 mg and placebo tablets
    31 Aug 2017
    • Added clinical pharmacology data and safety results from Cohort 1 from the PK lead-in phase supporting the dose for subjects 12 to < 18 years old (Group 1) in the treatment phase and dose determination for Cohort 2 (6 to < 12 years old) in the PK lead-in phase • Added an optional intensive PK substudy for adolescent subjects 12 to < 18 years old enrolled in the treatment phase at Weeks 4 or 8 to support development of the population PK model • Added additional time points to the intensive PK assessment for Cohort 3 (subjects 3 to < 6 years old) to support characterization of PK of all analytes in the youngest age group • Added clarification of the sparse PK sample at Weeks 1, 4, 8, and 12 • Added a second sparse PK sample at Weeks 4 and 8 for all enrolled subjects • Clarified that the non-tablet formulation information would be included in a future protocol amendment once it was available and would be submitted for approval prior to dosing of subjects • Added biomarker testing to align with the Gilead Sciences (Gilead) protocol template • Updated the dosing instructions in the case of vomiting to align with the SOF/VEL label • Updated the background information to include Studies GS-US-342-1553 and GS US 342 1146 since both of these studies were not included in the SOF/VEL investigator’s brochure (IB)
    15 Jun 2018
    • Added clinical pharmacology data from Cohort 2 from the PK lead-in phase supporting the dose for subjects 3 to < 6 years old (Cohort 3) in the PK lead-in phase • Added dosing instructions for subjects 3 to < 6 years old • Added information on the oral granule formulation, including the dose for each age group and dosing instructions • Added subject dosing diary for subjects who were administered oral granules • Clarified dosing instructions for subjects 6 to < 12 years old • Clarified collection of parental height • Clarified requirements for the complete and symptom-directed physical examinations • Updated the disallowed and concomitant medication table to align with the table in the SOF/VEL FDC IB (Edition 5.0; dated 12 December 2017) • Updated the list of PK parameters to align with regulatory commitments • Updated the schedule of assessments for consistency

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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