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 Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With 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: NCT02249182
Recruitment Status : Completed
First Posted : September 25, 2014
Results First Posted : April 24, 2019
Last Update Posted : April 24, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE September 23, 2014
First Posted Date  ICMJE September 25, 2014
Results First Submitted Date  ICMJE February 15, 2019
Results First Posted Date  ICMJE April 24, 2019
Last Update Posted Date April 24, 2019
Actual Study Start Date  ICMJE November 5, 2014
Actual Primary Completion Date June 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2019)
  • For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF), LDV, and SOF [ 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 ]
    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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 23, 2014)
  • For the PK Lead-in Phase, PK parameters of GS-331007 and LDV as measured by AUCtau to determine the appropriate LDV/SOF FDC dose. [ Time Frame: Day 10 ]
    For Cohorts 1 and 2, PK will be analyzed on Day 10 at the following time points: predose, 0.5, 1, 2, 3, 4, 5, 8, and 12 hours postdose. For Cohort 3, PK will be analyzed on Day 10 at the following time points: predose, 0.5, 2, 4, 8, and 12 hours postdose.
    • AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
  • For the Treatment Phase, any adverse event leading to permanent discontinuation of study drug(s) [ Time Frame: Up to 12 weeks ]
  • 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 after the last dose of study drug.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 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 ]
  • 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 10 ]
  • 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 < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4 weeks after stopping study treatment.
  • 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 < LLOQ at 12 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.
  • 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.
  • Acceptability of LDV/SOF Tablets as Measured by the Percentage of Participants Able/Unable to Swallow Placebo Tablet at Day 1 [ Time Frame: 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.
  • Acceptability of LDV/SOF Granules as Measured by Palatability at Day 1 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2014)
  • For the PK Lead-in Phase, early viral kinetics and PK profiles of GS-331007, sofosbuvir, and ledipasvir [ Time Frame: Day 10 ]
    For Cohorts 1 and 2, PK will be analyzed on Day 10 at the following time points: predose, 0.5, 1, 2, 3, 4, 5, 8, and 12 hours postdose. For Cohort 3, PK will be analyzed on Day 10 at the following time points: predose, 0.5, 2, 4, 8, and 12 hours postdose. This endpoint will measure the plasma PK profiles of GS-331007, sofosbuvir, and ledipasvir. The following parameters will be measured, where applicable:
    • AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
    • Cmax: maximum observed concentration of drug in plasma
    • AUClast: concentration of drug from time zero to the last quantifiable concentration
    • Tmax: time of Cmax
    • Clast: last observable concentration of drug
    • Tlast: time of Clast
    • Ctau: observed drug concentration at the end of the dosing interval
    • t1/2: estimate of the terminal elimination half-life of the drug
  • For the PK Lead-in Phase, adverse events leading to permanent discontinuation of study drug(s) [ Time Frame: Up to 10 days ]
  • For the Treatment Phase, growth and development measurements such as height, weight, and Tanner Stage Assessment [ Time Frame: Up to Posttreatment Week 24 ]
  • For the Treatment Phase, proportion of participants with sustained virologic response (SVR) at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ]
    SVR4 and SVR24 are defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
  • For the Treatment Phase, proportion of participants experiencing viral breakthrough [ Time Frame: Up to 12 weeks ]
    Viral breakthrough is defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) during treatment, but did not achieve a sustained virologic response (SVR).
  • For the Treatment Phase, proportion of participants experiencing viral relapse [ Time Frame: Week 12 to Posttreatment Week 24 ]
    Viral relapse is defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) within 4 weeks of end of treatment, but did not achieve an SVR.
  • For the Treatment Phase, HCV RNA change from baseline [ Time Frame: Up to 12 weeks ]
  • For the Treatment Phase, alanine aminotransferase (ALT) normalization [ Time Frame: Up to 12 weeks ]
    The proportion of participants with ALT normalization (defined as ALT > upper limit of the normal range (ULN) at Baseline and ALT ≤ ULN at each visit) will be summarized.
  • For the Treatment Phase, viral kinetic parameters [ Time Frame: Up to 12 weeks ]
    Viral kinetic parameters will be determined by the slope of viral load decline over time.
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 Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With Chronic HCV-Infection
Official Title  ICMJE 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
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.

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: 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 Name: REBETOL®
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: LDV/SOF
    • Drug: RBV
  • 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
    Interventions:
    • Drug: LDV/SOF
    • Drug: RBV
  • 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
    Interventions:
    • Drug: LDV/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: January 5, 2018)
226
Original Estimated Enrollment  ICMJE
 (submitted: September 23, 2014)
200
Actual Study Completion Date  ICMJE August 24, 2018
Actual Primary Completion Date June 15, 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
  • 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.

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,   New Zealand,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02249182
Other Study ID Numbers  ICMJE GS-US-337-1116
2014-003578-17 ( 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
Plan to Share IPD: Yes
Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at www.gilead.com/about/ethics-and-code-of-conduct/policies.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: https://www.gilead.com/about/ethics-and-code-of-conduct/policies
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 March 2019

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