Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children With Genotype 2 or 3 Chronic HCV Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02175758
Recruitment Status : Completed
First Posted : June 26, 2014
Results First Posted : April 30, 2019
Last Update Posted : April 30, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE June 24, 2014
First Posted Date  ICMJE June 26, 2014
Results First Submitted Date  ICMJE February 28, 2019
Results First Posted Date  ICMJE April 30, 2019
Last Update Posted Date April 30, 2019
Actual Study Start Date  ICMJE July 7, 2014
Actual Primary Completion Date June 21, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2019)
  • For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF) [ Time Frame: 6 to < 18 years of age: predose, 0.5, 1, 2, 3, 4, 8, and 12 hours postdose on Day 7; 3 to < 6 years of age: predose, 2, 4, 8, and 12 hours postdose on Day 7 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
  • Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase or the Treatment Phase [ Time Frame: Up to 24 weeks ]
  • For the Treatment Phase, Percentage of Participants With SVR at 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
    SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: June 24, 2014)
  • For the PK Lead-in Phase, PK parameters of GS-331007 as measured by AUCtau for determining the appropriate SOF dose [ Time Frame: Day 7 ]
    - AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
  • For the Treatment Phase, proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
    SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
  • For the Treatment Phase, incidence of any adverse event leading to permanent discontinuation of study drug(s) [ Time Frame: Up to 24 weeks ]
Change History Complete list of historical versions of study NCT02175758 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2019)
  • For Participants in the PK Lead-in Phase, Change From Baseline in HCV RNA [ Time Frame: Baseline; Weeks 1, 2, 4, 8, and 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only) ]
  • Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase [ Time Frame: Up to Day 7 ]
  • For the Treatment Phase, Percentage of Participants With Sustained Virologic Response (SVR) at 4 Weeks After Discontinuation of Therapy (SVR4) [ Time Frame: Posttreatment Week 4 ]
    SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.
  • For the Treatment Phase, Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) [ Time Frame: Posttreatment Week 24 ]
    SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.
  • For the Treatment Phase, Percentage of Participants Experiencing Viral Breakthrough [ Time Frame: Up to 24 weeks ]
    Viral breakthrough was defined as having confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment.
  • For the Treatment Phase, Percentage of Participants Experiencing Viral Relapse [ Time Frame: 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.
  • For the Treatment Phase, Change From Baseline in HCV RNA [ 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) ]
  • For the Treatment Phase, Percentage of Participants With HCV RNA < LLOQ While On Treatment [ Time Frame: Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only) ]
  • For the Treatment Phase, Percentage of Participants With Alanine Aminotransferase (ALT) Normalization [ 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 ]
    ALT normalization was defined as ALT > the upper limit of normal (ULN) at baseline and ALT ≤ ULN at each visit. One participant in the 3 to < 6 Years Old 12 Weeks group had ALT > ULN at Baseline, but had no other available data.
  • For the Treatment Phase, Change From Baseline in Height [ 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 ]
  • For the Treatment Phase, Change From Baseline in Weight [ 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 ]
  • For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Pubic Hair [ Time Frame: 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.
  • For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Genitalia Development [ Time Frame: 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.
  • For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Pubic Hair [ Time Frame: 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.
  • For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Breast Development [ Time Frame: 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.
  • For the Treatment Phase, Palatability of SOF Granules at Day 1 as Assessed by the Percentage of Participants Able/Unable to Taste the SOF Oral Granules [ Time Frame: Day 1 ]
    Participants were asked if they were able to taste the SOF oral granules.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2014)
  • For the PK Lead-in Phase, PK parameters of GS-331007 and SOF as measured by AUCtau, Cmax, AUClast, Tmax, Clast, Tlast, Ctau, and t1/2 [ Time Frame: Day 7 ]
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
    • Cmax is defined as the maximum observed concentration of drug in plasma
    • AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration
    • Tmax is defined as the time of Cmax
    • Clast is defined as the last observable concentration of drug
    • Tlast is defined as the time of Clast
    • t1/2 is defined as the estimate of the terminal elimination half-life of the drug
  • For the PK Lead-in Phase, incidence of adverse events leading to permanent discontinuation of study drug(s) [ Time Frame: Up to 7 days ]
  • For the Treatment Phase, proportion of participants with sustained virologic response (SVR) at 4 weeks after discontinuation of therapy (SVR4) [ Time Frame: Posttreatment Week 4 ]
    SVR4 is defined as HCV RNA < LLOQ at 4 weeks following the last dose of study drug.
  • For the Treatment Phase, proportion of participants with sustained virologic response (SVR) at 24 weeks after discontinuation of therapy (SVR24) [ Time Frame: Posttreatment Week 24 ]
    SVR24 is defined as HCV RNA < LLOQ at 24 weeks following the last dose of study drug.
  • For the Treatment Phase, proportion of participants with virologic breakthrough [ Time Frame: Up to 24 weeks ]
    Viral breakthrough is defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment.
  • For the Treatment Phase, proportion of participants with virologic relapse [ Time Frame: End of treatment to posttreatment Week 24 ]
    Viral relapse is defined as HCV RNA ≥ LLOQ during the posttreatment period after having achieved HCV RNA < LLOQ at end of treatment.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children With Genotype 2 or 3 Chronic HCV Infection
Official Title  ICMJE A Phase 2, Open-Label, Multicenter, Multi-cohort, Single-Arm Study to Investigate the Safety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children With Genotype 2 or 3 Chronic HCV Infection
Brief Summary

This study will have two parts as follows:

The PK Lead-in Phase of the study will evaluate the steady state pharmacokinetics (PK) and confirm the dose of sofosbuvir (SOF) in hepatitis C virus (HCV)-infected pediatric participants. The PK Lead-in Phase will also evaluate the safety and tolerability of 7 days of dosing of SOF+ribavirin (RBV) in HCV-infected pediatric participants.

The Treatment Phase will be initiated by age cohort after confirmation of age-appropriate SOF dosage levels. Participants from the PK Lead-in Phase will immediately rollover into the Treatment Phase with no interruption of study drug administration. The Treatment Phase will evaluate the antiviral efficacy, safety, and tolerability of SOF+RBV for 12 or 24 weeks in pediatric participants with genotype 2 or 3 HCV infection, respectively.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C Virus Infection
Intervention  ICMJE
  • Drug: SOF
    SOF administered orally once daily
    Other Names:
    • Sovaldi®
    • GS-7977
  • Drug: RBV
    RBV oral solution or capsules will be administered orally in a divided daily dose based on weight
    Other Name: REBETOL®
Study Arms  ICMJE
  • Experimental: 12 to < 18 Years Old, SOF+RBV 12 Weeks (GT 2)
    Participants between 12 to < 18 years of age with genotype (GT) 2 HCV infection weighing ≥ 45 kg will receive SOF (1 x 400 mg tablet, 4 x 100 mg tablets, or 8 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 12 weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: 12 to < 18 Years Old, SOF+RBV 24 Weeks (GT 3)
    Participants between 12 to < 18 years of age with genotype 3 HCV infection weighing ≥ 45 kg will receive SOF (1 x 400 mg tablet, 4 x 100 mg tablets, or 8 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 24 weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: 6 to < 12 Years Old, SOF+RBV 12 Weeks (GT 2)
    Participants between 6 to < 12 years of age with genotype 2 HCV infection weighing ≥ 17 kg and < 45 kg will receive SOF (2 x 100 mg tablets or 4 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 12 weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: 6 to <12 Years Old, SOF+RBV 24 Weeks (GT 3)
    Participants between 6 to < 12 years of age with genotype 3 HCV infection weighing ≥ 17 kg and < 45 kg will receive SOF (2 x 100 mg tablets or 4 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 24 weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: 3 to < 6 Years Old, SOF+RBV 12 Weeks (GT 2)
    Participants between 3 to < 6 years of age with genotype 2 HCV infection weighing ≥ 17kg will receive SOF (4 x 50 mg oral granules) plus RBV (up to 1400 mg) for 12 weeks and those weighing < 17 kg will receive SOF (3 x 50 mg oral granules) + RBV (up to 1400 mg) for 12 weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: 3 to < 6 Years Old, SOF+RBV 24 Weeks (GT 3)
    Participants between 3 to < 6 years of age with genotype 2 HCV infection weighing ≥ 17kg will receive SOF (4 x 50 mg oral granules) plus RBV (up to 1400 mg) for 24 weeks and those weighing < 17 kg will receive SOF (3 x 50 mg oral granules) + RBV (up to 1400 mg) for 24 weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 5, 2019)
106
Original Estimated Enrollment  ICMJE
 (submitted: June 24, 2014)
100
Actual Study Completion Date  ICMJE September 13, 2018
Actual Primary Completion Date June 21, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Consent of parent or legal guardian required
  • Chronic HCV infection genotype 2 or 3
  • Screening laboratory values within defined thresholds
  • PK Lead-in only: all individuals must be treatment naive

Key Exclusion Criteria:

  • History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
  • Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus
  • Clinical hepatic decompensation (ie, 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Germany,   Italy,   New Zealand,   Russian Federation,   United Kingdom,   United States
Removed Location Countries India
 
Administrative Information
NCT Number  ICMJE NCT02175758
Other Study ID Numbers  ICMJE GS-US-334-1112
2014-002283-32 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP