NCT02249182

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
226

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Nov 2014

Typical duration for phase_2

Geographic Reach
4 countries

31 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 23, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 25, 2014

Completed
1 month until next milestone

Study Start

First participant enrolled

November 5, 2014

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 15, 2018

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 24, 2018

Completed
8 months until next milestone

Results Posted

Study results publicly available

April 24, 2019

Completed
Last Updated

March 2, 2020

Status Verified

March 1, 2019

Enrollment Period

3.6 years

First QC Date

September 23, 2014

Results QC Date

February 15, 2019

Last Update Submit

February 18, 2020

Conditions

Hepatitis C Virus Infection

Outcome Measures

Primary Outcomes (2)

  • For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF), LDV, and SOF

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

    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

  • 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 Outcomes (18)

  • For Participants in the PK Lead-in Phase, Change From Baseline in HCV RNA

    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

    Up to Day 10

  • For the Treatment Phase, Percentage of Participants With Sustained Virologic Response (SVR) at 4 Weeks After Discontinuation of Therapy (SVR4)

    Posttreatment Week 4

  • For the Treatment Phase, Percentage of Participants With SVR at 12 Weeks After Discontinuation of Therapy (SVR12)

    Posttreatment Week 12

  • For the Treatment Phase, Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)

    Posttreatment Week 24

  • +13 more secondary outcomes

Study Arms (3)

12 to < 18 Years Old

EXPERIMENTAL

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/SOFDrug: RBV

6 to < 12 Years Old

EXPERIMENTAL

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/SOFDrug: RBV

3 to < 6 Years Old

EXPERIMENTAL

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/SOFDrug: RBV

Interventions

LDV/SOFDRUG

LDV/SOF FDC administered orally once daily

Also known as: Harvoni®, GS-5885/GS-7977
12 to < 18 Years Old3 to < 6 Years Old6 to < 12 Years Old
RBVDRUG

Ribavirin (RBV) oral solution or capsules will be administered orally in a divided daily dose based on weight

Also known as: REBETOL®
12 to < 18 Years Old3 to < 6 Years Old6 to < 12 Years Old

Eligibility Criteria

Age3 Years - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Consent of parent or legal guardian required
  • Chronic HCV infection
  • Screening laboratory values within defined thresholds

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (31)

Unknown Facility

Birmingham, Alabama, United States

Location

Unknown Facility

Los Angeles, California, United States

Location

Unknown Facility

San Francisco, California, United States

Location

Unknown Facility

Aurora, Colorado, United States

Location

Unknown Facility

Washington D.C., District of Columbia, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Indianapolis, Indiana, United States

Location

Unknown Facility

Louisville, Kentucky, United States

Location

Unknown Facility

Baltimore, Maryland, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Omaha, Nebraska, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Chapel Hill, North Carolina, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Columbus, Ohio, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Nashville, Tennessee, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

Fort Worth, Texas, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

Unknown Facility

Morgantown, West Virginia, United States

Location

Unknown Facility

Newcastle, New South Wales, Australia

Location

Unknown Facility

Westmead, New South Wales, Australia

Location

Unknown Facility

Parkville, Victoria, Australia

Location

Unknown Facility

Auckland, New Zealand

Location

Unknown Facility

Birmingham, England, United Kingdom

Location

Unknown Facility

Leeds, England, United Kingdom

Location

Unknown Facility

London, England, United Kingdom

Location

Unknown Facility

Glasgow, Scotland, United Kingdom

Location

Related Publications (10)

  • Kirby B, German P, Kanwar B, Ni L, Lakatos I, Ling J, Mathias A. Pharmacokinetics of Once-Daily Sofosbuvir and Ledipasvir/Sofosbuvir in HCV-Infected Adolescents. Hepatology 2015;62 (S1): 1040A-1041A

    RESULT

  • Garrison KL, Mathias A, Kersey K, Kanwar B, Ni L, Jain A, et al. Pharmacokinetics of Once-Daily Sofosbuvir and Ledipasvir/Sofosbuvir in HCV-Infected Pediatrics Aged 6 to < 12 Years Old. Hepatology 2016;64 (S1): 436A

    RESULT

  • Schwarz K, Murray KF, Rosenthal P, Bansal S, Lin CH, Ni L, et al. High Rates of SVR12 in Adolescents Treated with the Combination of Ledipasvir/Sofosbuvir. J Hepatol 2016; 64 (2): S184-S185

    RESULT

  • K.F. Murray, W. Balistreri, S. Bansal, S. Whitworth, H. Evans, R.P. Gonzalez-Peralta, et al. Ledipasvir/sofosbuvir ± ribavirin for 12 or 24 weeks is safe and effective in children 6-11 years old with chronic hepatitis C infection. J Hepatol 2017;66: S33-S62

    RESULT

  • Balistreri WF, Murray KF, Rosenthal P, Bansal S, Lin CH, Kersey K, Massetto B, Zhu Y, Kanwar B, German P, Svarovskaia E, Brainard DM, Wen J, Gonzalez-Peralta RP, Jonas MM, Schwarz K. The safety and effectiveness of ledipasvir-sofosbuvir in adolescents 12-17 years old with hepatitis C virus genotype 1 infection. Hepatology. 2017 Aug;66(2):371-378. doi: 10.1002/hep.28995. Epub 2017 Jun 19.

    PMID: 27997679RESULT

  • Younossi ZM, Stepanova M, Balistreri W, Schwarz K, Murray KF, Rosenthal P, Bansal S, Hunt S. Health-related Quality of Life in Adolescent Patients With Hepatitis C Genotype 1 Treated With Sofosbuvir and Ledipasvir. J Pediatr Gastroenterol Nutr. 2018 Jan;66(1):112-116. doi: 10.1097/MPG.0000000000001754.

    PMID: 28957984RESULT

  • Begley R, Meng A, Massetto B, Shao J, Ling J, and Mathias A. Pharmacokinetics of Once Daily Sofosbuvir or Ledipasvir/Sofosbuvir in HCV-Infected Pediatrics Aged 3 to <6 Years Old. Hepatology 2018;68 (S1): 582A.

    RESULT

  • Schwarz KB, Rosenthal P, Murray KF, Honegger JR, Hardikar W, Hague R, et al. Ledipasvir/Sofosbuvir for 12 Weeks Is Safe and Effective in Children 3 to <6 Years Old with Chronic Hepatitis C Virus Infection. Hepatology 2018;68 (S1): 116A-117A.

    RESULT

  • Murray KF, Balistreri WF, Bansal S, Whitworth S, Evans HM, Gonzalez-Peralta RP, Wen J, Massetto B, Kersey K, Shao J, Garrison KL, Parhy B, Brainard DM, Arnon R, Gillis LA, Jonas MM, Lin CH, Narkewicz MR, Schwarz K, Rosenthal P. Safety and Efficacy of Ledipasvir-Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11. Hepatology. 2018 Dec;68(6):2158-2166. doi: 10.1002/hep.30123. Epub 2018 Nov 17.

    PMID: 30070726RESULT

  • Schwarz KB, Rosenthal P, Murray KF, Honegger JR, Hardikar W, Hague R, Mittal N, Massetto B, Brainard DM, Hsueh CH, Shao J, Parhy B, Narkewicz MR, Rao GS, Whitworth S, Bansal S, Balistreri WF. Ledipasvir-Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C. Hepatology. 2020 Feb;71(2):422-430. doi: 10.1002/hep.30830. Epub 2019 Aug 19.

    PMID: 31220349DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

ledipasvir, sofosbuvir drug combinationRibavirin

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

RibonucleosidesNucleosidesNucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

Title
Gilead Clinical Study Information Center
Organization
Gilead Sciences
GileadClinicalTrials@gilead.com
1-833-445-3230 (GILEAD-0)

Study Officials

  • Gilead Study Director

    Gilead Sciences

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 23, 2014

First Posted

September 25, 2014

Study Start

November 5, 2014

Primary Completion

June 15, 2018

Study Completion

August 24, 2018

Last Updated

March 2, 2020

Results First Posted

April 24, 2019

Record last verified: 2019-03

Data Sharing

IPD Sharing
Will share

Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
18 months after study completion
Access Criteria
A secured external environment with username, password, and RSA code.
More information

Locations

US(23)GB(4)AU(3)NZ(1)