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

This study is currently recruiting participants.
Verified October 2017 by Gilead Sciences
Sponsor:
ClinicalTrials.gov Identifier:
NCT02249182
First Posted: September 25, 2014
Last Update Posted: October 12, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Gilead Sciences
  Purpose

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 ledipasvir/sofobuvir (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 Treatment Phase will evaluate the antiviral efficacy, safety, and tolerability of LDV/SOF FDC +/- Ribavirin (RBV) for 12 or 24 weeks in pediatric participants with HCV.


Condition Intervention Phase
Hepatitis C Virus Infection Drug: LDV/SOF Drug: Placebo to match LDV/SOF Drug: RBV Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • For the PK Lead-in Phase, PK parameters of GS-331007, SOF, 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 24 weeks ]

Secondary Outcome Measures:
  • For the PK Lead-in Phase, serum HCV RNA values and change from baseline [ Time Frame: Up to 10 days ]
    Antiviral activity measurements including serum HCV RNA values and change from baseline will be summarized at each visit.

  • 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 as measured by height [ Time Frame: Up to Posttreatment Week 24 ]
  • For the Treatment Phase, growth and development as measured by weight [ Time Frame: Up to Posttreatment Week 24 ]
  • For the Treatment Phase, growth and development as measured by Tanner Stage Assessment [ Time Frame: Up to Posttreatment Week 24 ]
  • For the Treatment Phase, proportion of participants with sustained virologic response (SVR) at 12 weeks after discontinuation of therapy (SVR12) [ Time Frame: Posttreatment Weeks 12 ]
    SVR12 is defined as HCV RNA < LLOQ at 12 weeks following the last dose of study drug, respectively.

  • 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 24 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 8 weeks ]
  • For the Treatment Phase, alanine aminotransferase (ALT) normalization [ Time Frame: Up to 24 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 24 weeks ]
    Viral kinetic parameters will be determined by the slope of viral load decline over time.

  • For the Treatment Phase, acceptability of LDV/SOF tablets as measured by a question form to assess swallowability at Day 1 [ Time Frame: Day 1 ]
  • For the Treatment Phase, acceptability of LDV/SOF granules as measured by a question form to assess palatability at Day 1 [ Time Frame: Day 1 ]

Estimated Enrollment: 220
Actual Study Start Date: November 5, 2014
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PK Lead-in Phase, Cohort 1
During screening, participants will receive placebo to match LDV/SOF FDC to assess ability to swallow. After screening, participants between 12 to < 18 years of age weighing ≥ 45 kg will receive LDV/SOF FDC 90 mg/400 mg for 10 days (or LDV/SOF FDC 4 x 22.5 mg/100 mg based on swallowability assessment during screening).
Drug: LDV/SOF
LDV/SOF FDC tablet(s) administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: Placebo to match LDV/SOF
Placebo to match LDV/SOF FDC tablet administered orally once
Experimental: PK Lead-in Phase, Cohort 2
During screening, participants will receive placebo to match LDV/SOF FDC to assess ability to swallow. After screening, participants between 6 to < 12 years of age weighing ≥ 17 kg and < 45 kg will receive LDV/SOF FDC 2 x 22.5 mg/100 mg for 10 days.
Drug: LDV/SOF
LDV/SOF FDC tablet(s) administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: Placebo to match LDV/SOF
Placebo to match LDV/SOF FDC tablet administered orally once
Experimental: PK Lead-in Phase, Cohort 3
Participants between 3 to < 6 years of age weighing ≥ 17 kg will receive 45 mg/ 200 mg (4 x 11.25 mg/ 50 mg packets) LDV/SOF FDC and those weighing < 17 kg will receive 33.75 mg/ 150 mg (3 x 11.25 mg/ 50 mg packets) LDV/SOF FDC for 10 days.
Drug: LDV/SOF
LDV/SOF FDC granules administered orally once daily
Other Name: GS-5885/GS-7977
Experimental: Treatment Phase, Group 1

Participants not rolling over from the PK Lead-in Phase will receive placebo to match LDV/SOF FDC to assess ability to swallow during screening. Participants between 12 to < 18 years of age will receive LDV/SOF FDC 90 mg/400 mg (or LDV/SOF FDC 4 x 22.5 mg/100 mg based on swallowability assessment during screening).

HCV Genotype 1, 4, 5, or 6 (United Kingdom/ United States/Australia/New Zealand): Treatment naive with or without cirrhosis and treatment-experienced without cirrhosis will receive LDV/SOF FDC for 12 weeks. Treatment-experienced with cirrhosis will receive LDV/SOF FDC for 24 weeks.

HCV Genotype 4, 5, or 6 (United States/Australia/New Zealand): Treatment-naïve or treatment-experienced participants with or without cirrhosis: LDV/SOF FDC for 12 weeks

HCV Genotype 3 (United Kingdom): Treatment-experienced with or without cirrhosis participants will receive LDV/SOF FDC + RBV for 24 weeks.

Drug: LDV/SOF
LDV/SOF FDC tablet(s) administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: Placebo to match LDV/SOF
Placebo to match LDV/SOF FDC tablet administered orally once
Drug: RBV
Ribavirin (RBV) oral solution or capsules will be administered orally in a divided daily dose based on weight
Other Name: REBETOL®
Experimental: Treatment Phase, Group 2

Participants not rolling over from the PK Lead-in Phase will receive placebo to match LDV/SOF FDC to assess ability to swallow during screening. Participants between 3 to < 12 years of age will receive LDV/SOF FDC (age-appropriate dose and formulation pending PK and safety results from Cohort 2 in PK lead-in phase).

HCV Genotype 1, 4, 5, or 6 (United Kingdom/ United States/Australia/New Zealand): Treatment naive with or without cirrhosis and treatment-experienced without cirrhosis will receive LDV/SOF FDC for 12 weeks. Treatment-experienced with cirrhosis will receive LDV/SOF FDC for 24 weeks.

HCV Genotype 4, 5, or 6 (United States/Australia/New Zealand): Treatment-naïve or treatment-experienced participants with or without cirrhosis: LDV/SOF FDC for 12 weeks

HCV Genotype 3 (United Kingdom): Treatment-experienced with or without cirrhosis participants will receive LDV/SOF FDC + RBV for 24 weeks.

Drug: LDV/SOF
LDV/SOF FDC tablet(s) administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: Placebo to match LDV/SOF
Placebo to match LDV/SOF FDC tablet administered orally once
Drug: RBV
Ribavirin (RBV) oral solution or capsules will be administered orally in a divided daily dose based on weight
Other Name: REBETOL®

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   3 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Consent of parent or legal guardian required
  • Chronic HCV infection
  • Screening laboratory values within define 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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02249182


Contacts
Contact: Gilead Study Team 337-1116alerts@gilead.com

  Show 34 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Gilead Study Director Gilead Sciences
  More Information

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02249182     History of Changes
Other Study ID Numbers: GS-US-337-1116
First Submitted: September 23, 2014
First Posted: September 25, 2014
Last Update Posted: October 12, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Infection
Communicable Diseases
Hepatitis C
Virus Diseases
Hepatitis, Viral, Human
Flaviviridae Infections
RNA Virus Infections
Hepatitis
Liver Diseases
Digestive System Diseases
Ribavirin
Sofosbuvir
Ledipasvir
Ledipasvir, sofosbuvir drug combination
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents