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Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With Chronic HCV-Infection

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT02249182
Collaborator
(none)
226
Enrollment
31
Locations
3
Arms
45.6
Actual Duration (Months)
7.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of the PK Lead-in Phase of the study is to evaluate the steady state pharmacokinetics (PK) and confirm the dose of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) in hepatitis C virus (HCV)-infected pediatric participants. The PK Lead-in Phase will also evaluate the safety, tolerability, and antiviral activity of 10 days of dosing of LDV/SOF FDC in HCV-infected pediatric participants.

The Treatment Phase will be initiated by age cohort after confirmation of age-appropriate LDV/SOF FDC dosage levels. Participants from the PK Lead-in Phase will immediately rollover into the Treatment Phase with no interruption of study drug administration. The primary objective of the Treatment Phase is to evaluate the antiviral efficacy, safety, and tolerability of LDV/SOF FDC +/- ribavirin (RBV) for 12 or 24 weeks in pediatric participants with HCV.

During screening, participants will receive placebo to match LDV/SOF FDC to assess ability to swallow tablets.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
226 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 Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With Chronic HCV-Infection
Actual Study Start Date :
Nov 5, 2014
Actual Primary Completion Date :
Jun 15, 2018
Actual Study Completion Date :
Aug 24, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: 12 to < 18 Years Old

Participants between 12 to < 18 years of age weighing ≥ 45 kg will receive LDV/SOF FDC (90/400 mg tablet or 4 x 22.5 mg/100 mg tablets or 8 x 11.25/50 mg granules based on swallowability assessment during screening). Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment. United Kingdom: HCV genotypes (GT) 1, 4, 5, or 6 treatment-naive (TN) with or without cirrhosis = LDV/SOF 12 weeks HCV GT 1, 4, 5, or 6 treatment-experienced (TE) without cirrhosis = LDV/SOF 12 weeks HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks United States/Australia/New Zealand: HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks

Drug: LDV/SOF
LDV/SOF FDC administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977

    • Drug: RBV
    Ribavirin (RBV) oral solution or capsules will be administered orally in a divided daily dose based on weight
    Other Names:
  • REBETOL®

    		•
    Experimental: 6 to < 12 Years Old

    Participants between 6 to < 12 years of age weighing ≥ 17 kg and < 45 kg will receive LDV/SOF FDC (45/200 mg as 2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules based on swallowability assessment during screening). Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment. United Kingdom: HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks United States/Australia/New Zealand: HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks

    Drug: LDV/SOF
    LDV/SOF FDC administered orally once daily
    Other Names:
  • Harvoni®
  • GS-5885/GS-7977

    • Drug: RBV
    Ribavirin (RBV) oral solution or capsules will be administered orally in a divided daily dose based on weight
    Other Names:
  • REBETOL®

    		•
    Experimental: 3 to < 6 Years Old

    Participants between 3 to < 6 years of age weighing ≥ 17 kg will receive LDV/SOF FDC (45/200 mg granules as 4 x 11.25/50 mg packets) and participants weighing < 17 kg will receive LDV/SOF FDC (33.75/150 mg oral granules as 3 x 11.25/50 mg packets). Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment. United Kingdom: HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks United States/Australia/New Zealand: HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks

    Drug: LDV/SOF
    LDV/SOF FDC administered orally once daily
    Other Names:
  • Harvoni®
  • GS-5885/GS-7977

    • Drug: RBV
    Ribavirin (RBV) oral solution or capsules will be administered orally in a divided daily dose based on weight
    Other Names:
  • REBETOL®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF), LDV, and SOF [Cohorts 1 and 2 (6 to < 18 years of age): predose, 0.5, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10; Cohort 3 (3 to < 6 years of age): predose, 0.5, 2, 4, 8, and 12 hours postdose on Day 10]

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

    2. Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase or the Treatment Phase [Up to 24 weeks]

    Secondary Outcome Measures

    1. For Participants in the PK Lead-in Phase, Change From Baseline in HCV RNA [Baseline; Weeks 1, 2, 4, 8, and 12]

    2. Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase [Up to Day 10]

    3. For the Treatment Phase, Percentage of Participants With Sustained Virologic Response (SVR) at 4 Weeks After Discontinuation of Therapy (SVR4) [Posttreatment Week 4]

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

    4. For the Treatment Phase, Percentage of Participants With SVR at 12 Weeks After Discontinuation of Therapy (SVR12) [Posttreatment Week 12]

      SVR12 was defined as HCV RNA < LLOQ at 12 weeks after stopping study treatment.

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

      SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.

    6. For the Treatment Phase, Percentage of Participants Experiencing Viral Breakthrough [Up to 24 weeks]

      Viral breakthrough was defined as having confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment.

    7. For the Treatment Phase, Percentage of Participants Experiencing Viral Relapse [Up to Posttreatment Week 24]

      Viral relapse was defined as having confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

    8. For the Treatment Phase, Change From Baseline in HCV RNA [Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)]

    9. For the Treatment Phase, Percentage of Participants With HCV RNA < LLOQ While On Treatment [Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)]

    10. For the Treatment Phase, Percentage of Participants With Alanine Aminotransferase (ALT) Normalization [Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Week 4]

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

    11. For the Treatment Phase, Change From Baseline in Height [Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Weeks 4, 12, and 24]

    12. For the Treatment Phase, Change From Baseline in Weight [Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Weeks 4, 12, and 24]

    13. For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Pubic Hair [Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24]

      Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.

    14. For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Genitalia Development [Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24]

      Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.

    15. For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Pubic Hair [Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24]

      Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.

    16. For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Breast Development [Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24]

      Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.

    17. Acceptability of LDV/SOF Tablets as Measured by the Percentage of Participants Able/Unable to Swallow Placebo Tablet at Day 1 [Day 1]

      Participants who were able/unable to swallow placebo tablets were assessed. Participants 12 to < 18 years old were first asked to perform the swallowability assessment using the 90/400 mg placebo tablet. If they were unable to swallow this, they were then asked to perform the swallowability assessment with 22.5/100 mg placebo tablets. Participants 6 to < 12 years old were to be assessed with the 22.5/100 mg placebo tablets. However, 8 participants were mistakenly assessed using the 90/400 mg placebo tablet.

    18. Acceptability of LDV/SOF Granules as Measured by Palatability at Day 1 [Day 1]

      Participants who were dosed with granules were asked if they tasted the study drug. If they tasted it, then they were asked to provide a number from 0 to 100 to rate the taste of the study drug, with higher scores indicating better taste. Data was then summarized as percentage of participants choosing the following palatability categories: 1) Did not taste the study drug, 2) Tasted drug with score > 60 to 100, 3) Tasted drug with score 40 to 60, and 4) Tasted drug with score of 0 to < 40.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    3 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Consent of parent or legal guardian required

    • Chronic HCV infection

    • Screening laboratory values within defined thresholds

    Key Exclusion Criteria:

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

    • Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus

    • Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage)

    • Pregnant or nursing females

    • Known hypersensitivity to study medication

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

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States
    2 Los Angeles California United States
    3 San Francisco California United States
    4 Aurora Colorado United States
    5 Washington District of Columbia United States
    6 Atlanta Georgia United States
    7 Indianapolis Indiana United States
    8 Louisville Kentucky United States
    9 Baltimore Maryland United States
    10 Boston Massachusetts United States
    11 Saint Louis Missouri United States
    12 Omaha Nebraska United States
    13 New York New York United States
    14 Chapel Hill North Carolina United States
    15 Cincinnati Ohio United States
    16 Columbus Ohio United States
    17 Philadelphia Pennsylvania United States
    18 Nashville Tennessee United States
    19 Dallas Texas United States
    20 Fort Worth Texas United States
    21 San Antonio Texas United States
    22 Seattle Washington United States
    23 Morgantown West Virginia United States
    24 Newcastle New South Wales Australia
    25 Westmead New South Wales Australia
    26 Parkville Victoria Australia
    27 Auckland New Zealand
    28 Birmingham England United Kingdom
    29 Leeds England United Kingdom
    30 London England United Kingdom
    31 Glasgow Scotland United Kingdom

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02249182
    Other Study ID Numbers:
    • GS-US-337-1116
    • 2014-003578-17
    First Posted:
    Sep 25, 2014
    Last Update Posted:
    Mar 2, 2020
    Last Verified:
    Mar 1, 2019
    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
    Ribavirin
    Sofosbuvir
    Ledipasvir, sofosbuvir drug combination
    Ledipasvir

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in the United States, United Kingdom, Australia, and New Zealand. The first participant was screened on 05 November 2014. The last study visit occurred on 24 August 2018.
    Pre-assignment Detail 240 participants were screened.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with hepatitis C virus (HCV) genotype 1 treatment-naive (TN) with or without cirrhosis or treatment-experienced (TE) without cirrhosis received ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants participating in the PK Lead-in Phase immediately rolled over into the Treatment Phase without interruption to study drug administration. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants participating in the PK Lead-in Phase immediately rolled over into the Treatment Phase without interruption to study drug administration. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin (RBV) capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks. Participants participating in the PK Lead-in Phase immediately rolled over into the Treatment Phase without interruption to study drug administration.
    Period Title: PK Lead-In Phase
    STARTED 10 12 0 0 17
    COMPLETED 10 12 0 0 17
    NOT COMPLETED 0 0 0 0 0
    Period Title: PK Lead-In Phase
    STARTED 100 89 1 2 34
    COMPLETED 96 89 1 2 34
    NOT COMPLETED 4 0 0 0 0

    Baseline Characteristics

    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks Total
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks. Total of all reporting groups
    Overall Participants 100 89 1 2 34 226
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    15
    (1.7)
    9
    (1.6)
    11
    (NA)
    9
    (2.8)
    4
    (0.7)
    11
    (4.1)
    Sex: Female, Male (Count of Participants)
    Female
    63
    63%
    36
    40.4%
    1
    100%
    1
    50%
    24
    70.6%
    125
    55.3%
    Male
    37
    37%
    53
    59.6%
    0
    0%
    1
    50%
    10
    29.4%
    101
    44.7%
    Race/Ethnicity, Customized (Count of Participants)
    White
    91
    91%
    70
    78.7%
    1
    100%
    2
    100%
    27
    79.4%
    191
    84.5%
    Black or African American
    7
    7%
    7
    7.9%
    0
    0%
    0
    0%
    1
    2.9%
    15
    6.6%
    Other
    0
    0%
    5
    5.6%
    0
    0%
    0
    0%
    4
    11.8%
    9
    4%
    Asian
    2
    2%
    5
    5.6%
    0
    0%
    0
    0%
    2
    5.9%
    9
    4%
    Native Hawaiian or Pacific Islander
    0
    0%
    2
    2.2%
    0
    0%
    0
    0%
    0
    0%
    2
    0.9%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    13
    13%
    9
    10.1%
    0
    0%
    0
    0%
    6
    17.6%
    28
    12.4%
    Not Hispanic or Latino
    85
    85%
    75
    84.3%
    1
    100%
    2
    100%
    28
    82.4%
    191
    84.5%
    Not Disclosed
    2
    2%
    5
    5.6%
    0
    0%
    0
    0%
    0
    0%
    7
    3.1%
    Region of Enrollment (Count of Participants)
    New Zealand
    0
    0%
    4
    4.5%
    0
    0%
    0
    0%
    0
    0%
    4
    1.8%
    United States
    91
    91%
    70
    78.7%
    0
    0%
    0
    0%
    29
    85.3%
    190
    84.1%
    United Kingdom
    1
    1%
    9
    10.1%
    0
    0%
    2
    100%
    3
    8.8%
    15
    6.6%
    Australia
    8
    8%
    6
    6.7%
    1
    100%
    0
    0%
    2
    5.9%
    17
    7.5%
    HCV Genotype (Count of Participants)
    Genotype 1
    100
    100%
    87
    97.8%
    1
    100%
    0
    0%
    33
    97.1%
    221
    97.8%
    Genotype 3
    0
    0%
    0
    0%
    0
    0%
    2
    100%
    0
    0%
    2
    0.9%
    Genotype 4
    0
    0%
    2
    2.2%
    0
    0%
    0
    0%
    1
    2.9%
    3
    1.3%
    Cirrhosis Status (Count of Participants)
    Yes
    1
    1%
    1
    1.1%
    1
    100%
    0
    0%
    0
    0%
    3
    1.3%
    No
    43
    43%
    33
    37.1%
    0
    0%
    2
    100%
    14
    41.2%
    92
    40.7%
    Unknown
    56
    56%
    55
    61.8%
    0
    0%
    0
    0%
    20
    58.8%
    131
    58%
    IL28b Status (Count of Participants)
    CC
    24
    24%
    23
    25.8%
    0
    0%
    0
    0%
    10
    29.4%
    57
    25.2%
    CT
    53
    53%
    53
    59.6%
    0
    0%
    2
    100%
    16
    47.1%
    124
    54.9%
    TT
    23
    23%
    12
    13.5%
    1
    100%
    0
    0%
    6
    17.6%
    42
    18.6%
    Missing
    0
    0%
    1
    1.1%
    0
    0%
    0
    0%
    2
    5.9%
    3
    1.3%
    HCV RNA Category (Count of Participants)
    < 800,000 IU/mL
    45
    45%
    37
    41.6%
    0
    0%
    1
    50%
    15
    44.1%
    98
    43.4%
    ≥ 800,000 IU/mL
    55
    55%
    52
    58.4%
    1
    100%
    1
    50%
    19
    55.9%
    128
    56.6%
    Prior Treatment Experience (Count of Participants)
    Treatment-Naive
    80
    80%
    72
    80.9%
    0
    0%
    0
    0%
    34
    100%
    186
    82.3%
    Treatment-Experienced
    20
    20%
    17
    19.1%
    1
    100%
    2
    100%
    0
    0%
    40
    17.7%

    Outcome Measures

    1. Primary Outcome
    Title For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF), LDV, and 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 Cohorts 1 and 2 (6 to < 18 years of age): predose, 0.5, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10; Cohort 3 (3 to < 6 years of age): predose, 0.5, 2, 4, 8, and 12 hours postdose on Day 10

    Outcome Measure Data

    Analysis Population Description
    Intensive PK Analysis Set included all participants in the PK lead-in phase who received at least 1 dose of study drug and for whom at least 1 nonmissing PK concentration value, during the intensive sampling period, was reported by the PK laboratory.
    Arm/Group Title PK Lead-in: 12 to < 18 Years Old - LDV/SOF 12 Weeks PK Lead-in: 6 to < 12 Years Old - LDV/SOF 12 Weeks PK Lead-in: 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age weighing ≥ 45 kg received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age weighing ≥ 17 kg and < 45 kg received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 3 to < 6 years of age received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 10 10 13
    GS-331007 (metabolite of SOF)
    12682.5
    (1732.66)
    8210.3
    (2542.42)
    11688.9
    (3400.79)
    LDV
    10202.4
    (5196.49)
    7288.3
    (4547.33)
    9316.3
    (3280.51)
    SOF
    2175.7
    (578.92)
    1754.4
    (419.18)
    2495.2
    (412.64)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PK Lead-in: 12 to < 18 Years Old - LDV/SOF 12 Weeks
    Comments AUCtau of GS-331007 for the 12 to < 18 Years old group in the PK Lead-in Phase was compared against historical data collected in adult Phase 2/3 studies.
    Type of Statistical Test Equivalence
    Comments Equivalence was determined if the 90% confidence intervals (CI) were within the predefined equivalence boundaries of 50% to 200% for all age groups.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percentage Geometric Mean Ratio
    Estimated Value 105.20
    Confidence Interval (2-Sided) 90%
    90.61 to 122.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PK Lead-in: 6 to < 12 Years Old - LDV/SOF 12 Weeks
    Comments AUCtau of GS-331007 for the 6 to < 12 Years Old group in the PK Lead-in Phase was compared against historical data collected in adult Phase 2/3 studies.
    Type of Statistical Test Equivalence
    Comments Equivalence was determined if the 90% CIs were within the predefined equivalence boundaries of 50% to 200% for all age groups.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percentage Geometric Mean Ratio
    Estimated Value 65.76
    Confidence Interval (2-Sided) 90%
    56.62 to 76.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PK Lead-in: 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Comments AUCtau of GS-331007 for the 3 to < 6 Years Old group in the PK Lead-in Phase was compared against historical data collected in adult Phase 2/3 studies.
    Type of Statistical Test Equivalence
    Comments Equivalence was determined if the 90% CIs were within the predefined equivalence boundaries of 50% to 200% for all age groups.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percentage Geometric Mean Ratio
    Estimated Value 94.08
    Confidence Interval (2-Sided) 90%
    82.51 to 107.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PK Lead-in: 12 to < 18 Years Old - LDV/SOF 12 Weeks
    Comments AUCtau of LDV for the 12 to < 18 Years Old group in the PK Lead-in Phase was compared against historical data collected in adult Phase 2/3 studies.
    Type of Statistical Test Equivalence
    Comments Equivalence was determined if the 90% CIs were within the predefined equivalence boundaries of 50% to 200% for all age groups.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percentage Geometric Mean Ratio
    Estimated Value 127.18
    Confidence Interval (2-Sided) 90%
    94.89 to 170.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PK Lead-in: 6 to < 12 Years Old - LDV/SOF 12 Weeks
    Comments AUCtau of LDV for the 6 to < 12 Years Old group in the PK Lead-in Phase was compared against historical data collected in adult Phase 2/3 studies.
    Type of Statistical Test Equivalence
    Comments Equivalence was determined if the 90% CIs were within the predefined equivalence boundaries of 50% to 200% for all age groups.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percentage Geometric Mean Ratio
    Estimated Value 82.25
    Confidence Interval (2-Sided) 90%
    61.34 to 110.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PK Lead-in: 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Comments AUCtau of LDV for the 3 to < 6 Years Old group in the PK Lead-in Phase was compared against historical data collected in adult Phase 2/3 studies.
    Type of Statistical Test Equivalence
    Comments Equivalence was determined if the 90% CIs were within the predefined equivalence boundaries of 50% to 200% for all age groups.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percentage Geometric Mean Ratio
    Estimated Value 120.46
    Confidence Interval (2-Sided) 90%
    93.18 to 155.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PK Lead-in: 12 to < 18 Years Old - LDV/SOF 12 Weeks
    Comments AUCtau of SOF for the 12 to < 18 Years Old group in the PK Lead-in Phase was compared against historical data collected in adult Phase 2/3 studies.
    Type of Statistical Test Equivalence
    Comments Equivalence was determined if the 90% CIs were within the predefined equivalence boundaries of 50% to 200% for all age groups.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percentage Geometric Mean Ratio
    Estimated Value 159.88
    Confidence Interval (2-Sided) 90%
    137.89 to 185.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PK Lead-in: 6 to < 12 Years Old - LDV/SOF 12 Weeks
    Comments AUCtau of SOF for the 6 to < 12 Years Old group in the PK Lead-in Phase was compared against historical data collected in adult Phase 2/3 studies.
    Type of Statistical Test Equivalence
    Comments Equivalence was determined if the 90% CIs were within the predefined equivalence boundaries of 50% to 200% for all age groups.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percentage Geometric Mean Ratio
    Estimated Value 129.48
    Confidence Interval (2-Sided) 90%
    110.79 to 151.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PK Lead-in: 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Comments AUCtau of SOF for the 3 to < 6 Years Old group in the PK Lead-in Phase was compared against historical data collected in adult Phase 2/3 studies.
    Type of Statistical Test Equivalence
    Comments Equivalence was determined if the 90% CIs were within the predefined equivalence boundaries of 50% to 200% for all age groups.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percentage Geometric Mean Ratio
    Estimated Value 187.76
    Confidence Interval (2-Sided) 90%
    143.41 to 245.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase or the Treatment Phase
    Description
    Time Frame Up to 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set included all participants who were enrolled into the study and received at least 1 dose of study drug.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 100 89 1 2 34
    Number [percentage of participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2.9
    8.5%
    3. Secondary Outcome
    Title For Participants in the PK Lead-in Phase, Change From Baseline in HCV RNA
    Description
    Time Frame Baseline; Weeks 1, 2, 4, 8, and 12

    Outcome Measure Data

    Analysis Population Description
    Participants who were enrolled in the PK lead-in phase with available data were analyzed.
    Arm/Group Title PK Lead-in: 12 to < 18 Years Old - LDV/SOF 12 Weeks PK Lead-in: 6 to < 12 Years Old - LDV/SOF 12 Weeks PK Lead-in: 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age weighing ≥ 45 kg received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age weighing ≥ 17 kg and < 45 kg received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 3 to < 6 years of age received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 10 12 17
    Change at Week 1
    -4.34
    (0.621)
    -4.29
    (0.518)
    -4.32
    (0.616)
    Change at Week 2
    -4.71
    (0.651)
    -4.55
    (0.636)
    -4.87
    (0.724)
    Change at Week 4
    -4.73
    (0.667)
    -4.75
    (0.702)
    -4.92
    (0.715)
    Change at Week 8
    -4.73
    (0.667)
    -4.76
    (0.710)
    -4.92
    (0.715)
    Change at Week 12
    -4.73
    (0.667)
    -4.76
    (0.710)
    -4.92
    (0.715)
    4. Secondary Outcome
    Title Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase
    Description
    Time Frame Up to Day 10

    Outcome Measure Data

    Analysis Population Description
    Participants who were enrolled in the PK lead-in phase were analyzed.
    Arm/Group Title PK Lead-in: 12 to < 18 Years Old - LDV/SOF 12 Weeks PK Lead-in: 6 to < 12 Years Old - LDV/SOF 12 Weeks PK Lead-in: 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age weighing ≥ 45 kg received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age weighing ≥ 17 kg and < 45 kg received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 3 to < 6 years of age received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 10 12 17
    Number [percentage of participants]
    0
    0%
    0
    0%
    5.9
    590%
    5. Secondary Outcome
    Title For the Treatment Phase, Percentage of Participants With Sustained Virologic Response (SVR) at 4 Weeks After Discontinuation of Therapy (SVR4)
    Description SVR4 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4 weeks after stopping study treatment.
    Time Frame Posttreatment Week 4

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set included all participants who were enrolled into the study and received at least 1 dose of study drug.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 100 89 1 2 34
    Number (95% Confidence Interval) [percentage of participants]
    98.0
    98%
    98.9
    111.1%
    100.0
    10000%
    100.0
    5000%
    97.1
    285.6%
    6. Secondary Outcome
    Title For the Treatment Phase, Percentage of Participants With SVR at 12 Weeks After Discontinuation of Therapy (SVR12)
    Description SVR12 was defined as HCV RNA < LLOQ at 12 weeks after stopping study treatment.
    Time Frame Posttreatment Week 12

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 100 89 1 2 34
    Number (95% Confidence Interval) [percentage of participants]
    98.0
    98%
    98.9
    111.1%
    100.0
    10000%
    100.0
    5000%
    97.1
    285.6%
    7. Secondary Outcome
    Title For the Treatment Phase, Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)
    Description SVR24 was defined as HCV RNA < LLOQ 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 - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 100 89 1 2 34
    Number (95% Confidence Interval) [percentage of participants]
    98.0
    98%
    98.9
    111.1%
    100.0
    10000%
    100.0
    5000%
    97.1
    285.6%
    8. Secondary Outcome
    Title For the Treatment Phase, Percentage of Participants Experiencing Viral Breakthrough
    Description Viral breakthrough was defined as having confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment.
    Time Frame Up to 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 100 89 1 2 34
    Number [percentage of participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9. Secondary Outcome
    Title For the Treatment Phase, Percentage of Participants Experiencing Viral Relapse
    Description Viral relapse was defined as having 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 - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 100 89 1 2 34
    Number [percentage of participants]
    0
    0%
    1.1
    1.2%
    0
    0%
    0
    0%
    0
    0%
    10. Secondary Outcome
    Title For the Treatment Phase, Change From Baseline in HCV RNA
    Description
    Time Frame Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed. Participants from the 12 Weeks groups were not analyzed for Change at Weeks 16, 20, and 24 because they were only treated for 12 weeks.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 100 89 1 2 34
    Change at Week 1
    -4.34
    (0.634)
    -4.27
    (0.592)
    -4.30
    (NA)
    -4.54
    (0.308)
    -4.25
    (0.505)
    Change at Week 2
    -4.74
    (0.585)
    -4.73
    (0.544)
    -5.09
    (NA)
    -4.54
    (0.308)
    -4.80
    (0.628)
    Change at Week 4
    -4.84
    (0.557)
    -4.87
    (0.592)
    -5.09
    (NA)
    -4.54
    (0.308)
    -4.85
    (0.628)
    Change at Week 8
    -4.85
    (0.556)
    -4.89
    (0.597)
    -5.09
    (NA)
    -4.54
    (0.308)
    -4.86
    (0.633)
    Change at Week 12
    -4.85
    (0.556)
    -4.89
    (0.597)
    -5.09
    (NA)
    -4.54
    (0.308)
    -4.86
    (0.633)
    Change at Week 16
    -5.09
    (NA)
    -4.54
    (0.308)
    Change at Week 20
    -5.09
    (NA)
    -4.54
    (0.308)
    Change at Week 24
    -5.09
    (NA)
    -4.54
    (0.308)
    11. Secondary Outcome
    Title For the Treatment Phase, Percentage of Participants With HCV RNA < LLOQ While On Treatment
    Description
    Time Frame Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed. Participants from the 12 Weeks groups were not analyzed for Weeks 16, 20, and 24 because they were only treated for 12 weeks.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 100 89 1 2 34
    Week 1
    40.0
    40%
    30.3
    34%
    0
    0%
    100.0
    5000%
    29.4
    86.5%
    Week 2
    75.0
    75%
    71.9
    80.8%
    100.0
    10000%
    100.0
    5000%
    78.8
    231.8%
    Week 4
    97.0
    97%
    96.6
    108.5%
    100.0
    10000%
    100.0
    5000%
    97.0
    285.3%
    Week 8
    100.0
    100%
    100.0
    112.4%
    100.0
    10000%
    100.0
    5000%
    100.0
    294.1%
    Week 12
    100.0
    100%
    100.0
    112.4%
    100.0
    10000%
    100.0
    5000%
    100.0
    294.1%
    Week 16
    100.0
    100%
    100.0
    112.4%
    Week 20
    100.0
    100%
    100.0
    112.4%
    Week 24
    100.0
    100%
    100.0
    112.4%
    12. Secondary Outcome
    Title For the Treatment Phase, Percentage of Participants With Alanine Aminotransferase (ALT) Normalization
    Description ALT normalization was defined as ALT > the upper limit of normal (ULN) at baseline and ALT ≤ ULN at each visit.
    Time Frame Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Week 4

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with ALT > ULN at Baseline with available data were analyzed. Participants from the 12 Weeks groups were not analyzed for Weeks 16, 20, and 24 because they were only treated for 12 weeks.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 49 72 1 2 27
    Week 1
    72.3
    72.3%
    75.7
    85.1%
    0
    0%
    50.0
    2500%
    63.0
    185.3%
    Week 2
    89.8
    89.8%
    84.8
    95.3%
    0
    0%
    50.0
    2500%
    84.0
    247.1%
    Week 4
    93.8
    93.8%
    93.1
    104.6%
    0
    0%
    100.0
    5000%
    96.0
    282.4%
    Week 8
    91.3
    91.3%
    90.1
    101.2%
    0
    0%
    100.0
    5000%
    92.0
    270.6%
    Week 12
    93.3
    93.3%
    95.5
    107.3%
    100.0
    10000%
    100.0
    5000%
    91.7
    269.7%
    Week 16
    100.0
    100%
    100.0
    112.4%
    Week 20
    100.0
    100%
    100.0
    112.4%
    Week 24
    100.0
    100%
    100.0
    112.4%
    Posttreatment Week 4
    90.2
    90.2%
    98.4
    110.6%
    100.0
    10000%
    91.3
    4565%
    13. Secondary Outcome
    Title For the Treatment Phase, Change From Baseline in Height
    Description
    Time Frame Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Weeks 4, 12, and 24

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Analysis Set with available data were analyzed. Participants from the 12 Weeks groups were not analyzed for Change at Weeks 16, 20, and 24 because they were only treated for 12 weeks.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 100 89 1 2 34
    Change at Week 1
    0.1
    (0.68)
    0.1
    (0.83)
    0.3
    (NA)
    0.7
    (1.13)
    0.2
    (1.24)
    Change at Week 2
    0.0
    (0.70)
    0.3
    (0.73)
    0.5
    (NA)
    0.5
    (0.85)
    0.3
    (0.72)
    Change at Week 4
    0.1
    (0.84)
    0.5
    (0.79)
    1.2
    (NA)
    0.6
    (0.92)
    0.7
    (0.79)
    Change at Week 8
    0.4
    (1.04)
    0.8
    (0.79)
    1.3
    (NA)
    0.8
    (0.92)
    1.0
    (0.82)
    Change at Week 12
    0.5
    (1.10)
    1.3
    (0.83)
    2.1
    (NA)
    1.1
    (1.41)
    1.6
    (0.98)
    Change at Week 16
    3.2
    (NA)
    1.4
    (1.06)
    Change at Week 20
    4.3
    (NA)
    1.6
    (0.85)
    Change at Week 24
    4.3
    (NA)
    2.5
    (1.48)
    Change at Posttreatment Week 4
    0.8
    (1.46)
    1.8
    (1.04)
    4.3
    (NA)
    2.4
    (1.27)
    2.1
    (1.13)
    Change at Posttreatment Week 12
    1.2
    (1.82)
    2.7
    (0.97)
    5.0
    (NA)
    3.4
    (1.56)
    3.3
    (1.18)
    Change at Posttreatment Week 24
    1.8
    (2.31)
    4.1
    (1.39)
    7.6
    (NA)
    5.6
    (0.85)
    4.7
    (1.31)
    14. Secondary Outcome
    Title For the Treatment Phase, Change From Baseline in Weight
    Description
    Time Frame Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Weeks 4, 12, and 24

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Analysis Set with available data were analyzed. Participants from the 12 Weeks groups were not analyzed for Change at Weeks 16, 20, and 24 because they were only treated for 12 weeks.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 100 89 1 2 34
    Change at Week 1
    0.1
    (1.00)
    0.3
    (0.51)
    -0.5
    (NA)
    0.3
    (1.34)
    0.1
    (0.39)
    Change at Week 2
    0.3
    (1.11)
    0.4
    (0.54)
    0.0
    (NA)
    0.3
    (1.77)
    0.2
    (0.44)
    Change at Week 4
    0.4
    (1.44)
    0.5
    (0.64)
    0.5
    (NA)
    0.7
    (1.91)
    0.3
    (0.64)
    Change at Week 8
    0.5
    (1.90)
    0.8
    (0.84)
    1.3
    (NA)
    0.6
    (2.33)
    0.5
    (0.66)
    Change at Week 12
    0.6
    (2.32)
    1.1
    (1.27)
    2.1
    (NA)
    0.9
    (2.90)
    0.6
    (0.70)
    Change at Week 16
    1.6
    (NA)
    1.2
    (3.68)
    Change at Week 20
    2.2
    (NA)
    1.8
    (3.96)
    Change at Week 24
    3.1
    (NA)
    2.4
    (3.68)
    Change at Posttreatment Week 4
    0.9
    (2.70)
    1.4
    (1.48)
    1.8
    (NA)
    2.2
    (3.68)
    1.1
    (1.09)
    Change at Posttreatment Week 12
    1.6
    (3.48)
    2.1
    (1.87)
    3.1
    (NA)
    3.7
    (2.90)
    1.2
    (0.93)
    Change at Posttreatment Week 24
    3.2
    (4.38)
    3.5
    (2.75)
    4.5
    (NA)
    5.7
    (1.41)
    2.0
    (1.57)
    15. Secondary Outcome
    Title For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Pubic Hair
    Description Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.
    Time Frame Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24

    Outcome Measure Data

    Analysis Population Description
    Male participants in the Safety Analysis Set with available data were analyzed.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF±RBV 12 or 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Male participants 12 to < 18 years of age received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Male participants 6 to < 12 years of age received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily ± RBV capsules or oral solution (dose depending on weight) for 12 or 24 weeks. Male participants 3 to < 6 years of age received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 37 54 10
    No Change
    35
    35%
    52
    58.4%
    10
    1000%
    Increase
    1
    1%
    1
    1.1%
    0
    0%
    Decrease
    0
    0%
    1
    1.1%
    0
    0%
    No Change
    32
    32%
    51
    57.3%
    9
    900%
    Increase
    3
    3%
    2
    2.2%
    0
    0%
    Decrease
    0
    0%
    1
    1.1%
    0
    0%
    No Change
    28
    28%
    48
    53.9%
    9
    900%
    Increase
    7
    7%
    4
    4.5%
    1
    100%
    Decrease
    0
    0%
    1
    1.1%
    0
    0%
    16. Secondary Outcome
    Title For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Genitalia Development
    Description Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.
    Time Frame Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24

    Outcome Measure Data

    Analysis Population Description
    Male participants in the Safety Analysis Set with available data were analyzed.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF±RBV 12 or 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Male participants 12 to < 18 years of age received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Male participants 6 to < 12 years of age received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily ± RBV capsules or oral solution (dose depending on weight) for 12 or 24 weeks. Male participants 3 to < 6 years of age received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 37 54 10
    No Change
    34
    34%
    52
    58.4%
    10
    1000%
    Increase
    1
    1%
    1
    1.1%
    0
    0%
    Decrease
    0
    0%
    1
    1.1%
    0
    0%
    No Change
    33
    33%
    50
    56.2%
    9
    900%
    Increase
    2
    2%
    4
    4.5%
    0
    0%
    Decrease
    0
    0%
    0
    0%
    0
    0%
    No Change
    29
    29%
    47
    52.8%
    10
    1000%
    Increase
    6
    6%
    6
    6.7%
    0
    0%
    Decrease
    0
    0%
    0
    0%
    0
    0%
    17. Secondary Outcome
    Title For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Pubic Hair
    Description Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.
    Time Frame Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24

    Outcome Measure Data

    Analysis Population Description
    Female participants in the Safety Analysis Set with available data were analyzed.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF±RBV 12 or 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Female participants 12 to < 18 years of age received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Female participants 6 to < 12 years of age received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily ± RBV capsules or oral solution (dose depending on weight) for 12 or 24 weeks. Female participants 3 to < 6 years of age received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 63 38 24
    No Change
    52
    52%
    34
    38.2%
    21
    2100%
    Increase
    9
    9%
    2
    2.2%
    0
    0%
    Decrease
    1
    1%
    0
    0%
    0
    0%
    No Change
    45
    45%
    31
    34.8%
    22
    2200%
    Increase
    15
    15%
    3
    3.4%
    0
    0%
    Decrease
    0
    0%
    0
    0%
    0
    0%
    No Change
    40
    40%
    27
    30.3%
    22
    2200%
    Increase
    21
    21%
    8
    9%
    0
    0%
    Decrease
    0
    0%
    0
    0%
    0
    0%
    18. Secondary Outcome
    Title For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Breast Development
    Description Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.
    Time Frame Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24

    Outcome Measure Data

    Analysis Population Description
    Female participants in the Safety Analysis Set with available data were analyzed.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF±RBV 12 or 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Female participants 12 to < 18 years of age received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Female participants 6 to < 12 years of age received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily ± RBV capsules or oral solution (dose depending on weight) for 12 or 24 weeks. Female participants 3 to < 6 years of age received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 63 38 24
    No Change
    53
    53%
    31
    34.8%
    21
    2100%
    Increase
    8
    8%
    5
    5.6%
    0
    0%
    Decrease
    1
    1%
    0
    0%
    0
    0%
    No Change
    49
    49%
    25
    28.1%
    21
    2100%
    Increase
    11
    11%
    8
    9%
    1
    100%
    Decrease
    0
    0%
    1
    1.1%
    0
    0%
    No Change
    43
    43%
    21
    23.6%
    21
    2100%
    Increase
    18
    18%
    14
    15.7%
    1
    100%
    Decrease
    0
    0%
    0
    0%
    0
    0%
    19. Secondary Outcome
    Title Acceptability of LDV/SOF Tablets as Measured by the Percentage of Participants Able/Unable to Swallow Placebo Tablet at Day 1
    Description Participants who were able/unable to swallow placebo tablets were assessed. Participants 12 to < 18 years old were first asked to perform the swallowability assessment using the 90/400 mg placebo tablet. If they were unable to swallow this, they were then asked to perform the swallowability assessment with 22.5/100 mg placebo tablets. Participants 6 to < 12 years old were to be assessed with the 22.5/100 mg placebo tablets. However, 8 participants were mistakenly assessed using the 90/400 mg placebo tablet.
    Time Frame Day 1

    Outcome Measure Data

    Analysis Population Description
    Participants between 6 to <18 years old in the Safety Analysis Set who performed the swallowability assessment were analyzed.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF±RBV 12 or 24 Weeks
    Arm/Group Description Participants 12 to < 18 years of age received placebo to match LDV/SOF FDC to assess ability to swallow tablets on Day 1. They then received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age received placebo to match LDV/SOF FDC to assess ability to swallow tablets on Day 1. They then received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily ± RBV capsules or oral solution (dose depending on weight) for 12 or 24 weeks.
    Measure Participants 100 92
    Able to Swallow 90/400 mg Placebo Tablet
    89.0
    89%
    100.0
    112.4%
    Unable to Swallow 90/400 mg Placebo Tablet
    11.0
    11%
    0
    0%
    Able to Swallow 22.5/100 mg Placebo Tablet
    72.7
    72.7%
    98.8
    111%
    Unable to Swallow 22.5/100 mg Placebo Tablet
    27.3
    27.3%
    1.2
    1.3%
    20. Secondary Outcome
    Title Acceptability of LDV/SOF Granules as Measured by Palatability at Day 1
    Description Participants who were dosed with granules were asked if they tasted the study drug. If they tasted it, then they were asked to provide a number from 0 to 100 to rate the taste of the study drug, with higher scores indicating better taste. Data was then summarized as percentage of participants choosing the following palatability categories: 1) Did not taste the study drug, 2) Tasted drug with score > 60 to 100, 3) Tasted drug with score 40 to 60, and 4) Tasted drug with score of 0 to < 40.
    Time Frame Day 1

    Outcome Measure Data

    Analysis Population Description
    Participants between 3 to <6 years old in the Safety Analysis Set who performed the palatability test were analyzed.
    Arm/Group Title 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 3 to < 6 years of age received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    Measure Participants 17
    Did not taste the study drug
    41.2
    41.2%
    Tasted drug with score > 60 to 100
    17.6
    17.6%
    Tasted drug with score 40 to 60
    11.8
    11.8%
    Tasted drug with score of 0 to < 40
    29.4
    29.4%

    Adverse Events

    Time Frame Adverse Events (AEs): First dose date up to Week 12 or 24 (depending on group) plus 30 days (includes AEs occurring during the PK Lead-in Phase); All-Cause Mortality: Up to Posttreatment Week 24
    Adverse Event Reporting Description Safety Analysis Set included all participants who were enrolled into the study and received at least 1 dose of study drug.
    Arm/Group Title 12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Arm/Group Description Participants 12 to < 18 years of age with HCV genotype 1 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 90/400 mg (1 x 90/400 mg tablet or 4 x 22.5/100 mg tablets) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotypes 1 or 4 TN with or without cirrhosis or HCV genotype 1 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 12 weeks. Participants 6 to < 12 years of age with HCV genotype 1 TE with cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily for 24 weeks. Participants 6 to < 12 years of age with HCV genotype 3 TE without cirrhosis received LDV/SOF FDC 45/200 mg (2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules) once daily + ribavirin capsules or oral solution (dose depending on weight) for 24 weeks. Participants 3 to < 6 years of age with HCV genotypes 1 or 4 TN without cirrhosis received LDV/SOF FDC (weight ≥ 17 kg: 45/200 mg granules; weight < 17 kg: 33.75/150 mg granules) once daily for 12 weeks.
    All Cause Mortality
    12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/100 (0%) 0/89 (0%) 0/1 (0%) 0/2 (0%) 0/34 (0%)
    Serious Adverse Events
    12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/100 (0%) 1/89 (1.1%) 0/1 (0%) 0/2 (0%) 0/34 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/100 (0%) 1/89 (1.1%) 0/1 (0%) 0/2 (0%) 0/34 (0%)
    Infections and infestations
    Gastroenteritis 0/100 (0%) 1/89 (1.1%) 0/1 (0%) 0/2 (0%) 0/34 (0%)
    Tooth abscess 0/100 (0%) 1/89 (1.1%) 0/1 (0%) 0/2 (0%) 0/34 (0%)
    Other (Not Including Serious) Adverse Events
    12 to < 18 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 12 Weeks 6 to < 12 Years Old - LDV/SOF 24 Weeks 6 to < 12 Years Old - LDV/SOF+RBV 24 Weeks 3 to < 6 Years Old - LDV/SOF 12 Weeks
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 62/100 (62%) 54/89 (60.7%) 1/1 (100%) 2/2 (100%) 22/34 (64.7%)
    Ear and labyrinth disorders
    Ear pain 0/100 (0%) 2/89 (2.2%) 0/1 (0%) 1/2 (50%) 0/34 (0%)
    Gastrointestinal disorders
    Abdominal pain 7/100 (7%) 14/89 (15.7%) 0/1 (0%) 0/2 (0%) 2/34 (5.9%)
    Abdominal pain upper 7/100 (7%) 3/89 (3.4%) 0/1 (0%) 0/2 (0%) 2/34 (5.9%)
    Diarrhoea 13/100 (13%) 11/89 (12.4%) 0/1 (0%) 0/2 (0%) 0/34 (0%)
    Mouth ulceration 0/100 (0%) 2/89 (2.2%) 0/1 (0%) 1/2 (50%) 1/34 (2.9%)
    Nausea 11/100 (11%) 9/89 (10.1%) 0/1 (0%) 1/2 (50%) 1/34 (2.9%)
    Vomiting 12/100 (12%) 12/89 (13.5%) 0/1 (0%) 1/2 (50%) 8/34 (23.5%)
    General disorders
    Fatigue 13/100 (13%) 13/89 (14.6%) 0/1 (0%) 1/2 (50%) 2/34 (5.9%)
    Pyrexia 2/100 (2%) 15/89 (16.9%) 0/1 (0%) 1/2 (50%) 7/34 (20.6%)
    Infections and infestations
    Conjunctivitis 0/100 (0%) 1/89 (1.1%) 0/1 (0%) 0/2 (0%) 2/34 (5.9%)
    Ear infection 0/100 (0%) 0/89 (0%) 0/1 (0%) 0/2 (0%) 2/34 (5.9%)
    Nasopharyngitis 7/100 (7%) 2/89 (2.2%) 0/1 (0%) 1/2 (50%) 1/34 (2.9%)
    Pharyngitis streptococcal 0/100 (0%) 3/89 (3.4%) 0/1 (0%) 0/2 (0%) 4/34 (11.8%)
    Upper respiratory tract infection 5/100 (5%) 7/89 (7.9%) 0/1 (0%) 0/2 (0%) 3/34 (8.8%)
    Injury, poisoning and procedural complications
    Fall 0/100 (0%) 1/89 (1.1%) 0/1 (0%) 1/2 (50%) 0/34 (0%)
    Skin abrasion 1/100 (1%) 1/89 (1.1%) 0/1 (0%) 0/2 (0%) 2/34 (5.9%)
    Musculoskeletal and connective tissue disorders
    Back pain 5/100 (5%) 3/89 (3.4%) 0/1 (0%) 0/2 (0%) 0/34 (0%)
    Nervous system disorders
    Dizziness 2/100 (2%) 5/89 (5.6%) 0/1 (0%) 0/2 (0%) 1/34 (2.9%)
    Headache 26/100 (26%) 16/89 (18%) 0/1 (0%) 1/2 (50%) 3/34 (8.8%)
    Product Issues
    Product taste abnormal 0/100 (0%) 0/89 (0%) 0/1 (0%) 0/2 (0%) 3/34 (8.8%)
    Psychiatric disorders
    Insomnia 1/100 (1%) 1/89 (1.1%) 0/1 (0%) 0/2 (0%) 2/34 (5.9%)
    Reproductive system and breast disorders
    Dysmenorrhoea 5/100 (5%) 0/89 (0%) 0/1 (0%) 0/2 (0%) 0/34 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 10/100 (10%) 11/89 (12.4%) 1/1 (100%) 1/2 (50%) 7/34 (20.6%)
    Epistaxis 2/100 (2%) 2/89 (2.2%) 1/1 (100%) 0/2 (0%) 2/34 (5.9%)
    Nasal congestion 6/100 (6%) 5/89 (5.6%) 1/1 (100%) 0/2 (0%) 2/34 (5.9%)
    Oropharyngeal pain 10/100 (10%) 10/89 (11.2%) 0/1 (0%) 0/2 (0%) 1/34 (2.9%)
    Rhinorrhoea 2/100 (2%) 3/89 (3.4%) 1/1 (100%) 0/2 (0%) 6/34 (17.6%)
    Skin and subcutaneous tissue disorders
    Dermatitis allergic 0/100 (0%) 0/89 (0%) 0/1 (0%) 1/2 (50%) 0/34 (0%)
    Dermatitis contact 4/100 (4%) 0/89 (0%) 0/1 (0%) 0/2 (0%) 2/34 (5.9%)
    Ecchymosis 2/100 (2%) 0/89 (0%) 0/1 (0%) 0/2 (0%) 2/34 (5.9%)
    Rash 1/100 (1%) 8/89 (9%) 0/1 (0%) 0/2 (0%) 3/34 (8.8%)
    Rash maculo-papular 0/100 (0%) 0/89 (0%) 0/1 (0%) 1/2 (50%) 0/34 (0%)
    Skin odour abnormal 0/100 (0%) 0/89 (0%) 0/1 (0%) 1/2 (50%) 0/34 (0%)

    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

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02249182
    Other Study ID Numbers:
    • GS-US-337-1116
    • 2014-003578-17
    First Posted:
    Sep 25, 2014
    Last Update Posted:
    Mar 2, 2020
    Last Verified:
    Mar 1, 2019