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

NCT ID: NCT02249182

Last Updated: 2020-03-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

226 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-05

Study Completion Date

2018-08-24

Brief Summary

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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

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Conditions

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Hepatitis C Virus Infection

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC administered orally once daily

RBV

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC administered orally once daily

RBV

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC administered orally once daily

RBV

Intervention Type DRUG

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

Interventions

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LDV/SOF

LDV/SOF FDC administered orally once daily

Intervention Type DRUG

RBV

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

Intervention Type DRUG

Other Intervention Names

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Harvoni® GS-5885/GS-7977 REBETOL®

Eligibility Criteria

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Inclusion Criteria

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

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
Minimum Eligible Age

3 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Birmingham, Alabama, United States

Site Status

Los Angeles, California, United States

Site Status

San Francisco, California, United States

Site Status

Aurora, Colorado, United States

Site Status

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

Site Status

Atlanta, Georgia, United States

Site Status

Indianapolis, Indiana, United States

Site Status

Louisville, Kentucky, United States

Site Status

Baltimore, Maryland, United States

Site Status

Boston, Massachusetts, United States

Site Status

St Louis, Missouri, United States

Site Status

Omaha, Nebraska, United States

Site Status

New York, New York, United States

Site Status

Chapel Hill, North Carolina, United States

Site Status

Cincinnati, Ohio, United States

Site Status

Columbus, Ohio, United States

Site Status

Philadelphia, Pennsylvania, United States

Site Status

Nashville, Tennessee, United States

Site Status

Dallas, Texas, United States

Site Status

Fort Worth, Texas, United States

Site Status

San Antonio, Texas, United States

Site Status

Seattle, Washington, United States

Site Status

Morgantown, West Virginia, United States

Site Status

Newcastle, New South Wales, Australia

Site Status

Westmead, New South Wales, Australia

Site Status

Parkville, Victoria, Australia

Site Status

Auckland, , New Zealand

Site Status

Birmingham, England, United Kingdom

Site Status

Leeds, England, United Kingdom

Site Status

London, England, United Kingdom

Site Status

Glasgow, Scotland, United Kingdom

Site Status

Countries

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United States Australia New Zealand United Kingdom

References

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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

Reference Type 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

Reference Type 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

Reference Type 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

Reference Type 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.

Reference Type RESULT
PMID: 27997679 (View on PubMed)

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.

Reference Type RESULT
PMID: 28957984 (View on PubMed)

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.

Reference Type 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.

Reference Type 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.

Reference Type RESULT
PMID: 30070726 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31220349 (View on PubMed)

Provided Documents

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Document Type: Study Protocol: Original

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Document Type: Study Protocol: Amendment 1

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Document Type: Study Protocol: Amendment 2

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Document Type: Study Protocol: Amendment 3

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Document Type: Study Protocol: Amendment 4

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Document Type: Study Protocol: Amendment 5

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Document Type: Study Protocol: Amendment 6

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Document Type: Statistical Analysis Plan

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Other Identifiers

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2014-003578-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-337-1116

Identifier Type: -

Identifier Source: org_study_id

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