Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11

Karen F. Murray, William F. Balistreri, Sanjay Bansal, Suzanne Whitworth, Helen M. Evans, Regino P. Gonzalez-Peralta, Jessica Wen, Benedetta Massetto, Kathryn Kersey, Jiang Shao, Kimberly L. Garrison, Bandita Parhy, Diana M. Brainard, Ronen Arnon, Lynette A. Gillis, Maureen M. Jonas, Chuan Hao Lin, Michael R. Narkewicz, Kathleen Schwarz, Philip Rosenthal

Research output: Contribution to journalArticle

Abstract

Currently, there are no interferon-free treatments available for hepatitis C virus (HCV)–infected patients younger than 12 years. We evaluated the safety and effectiveness of the all-oral regimen ledipasvir–sofosbuvir ± ribavirin in HCV-infected children aged 6 to <12 years. In an open-label study, patients aged 6 to <12 years received ledipasvir 45 mg–sofosbuvir 200 mg as two fixed-dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety-two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6-11). Most were perinatally infected (97%) and treatment-naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%-100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration–time curve and maximum concentration values for sofosbuvir, its primary metabolite GS-331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%-200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir–sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.

Original languageEnglish (US)
Pages (from-to)2158-2166
Number of pages9
JournalHepatology
Volume68
Issue number6
DOIs
StatePublished - Dec 1 2018

Fingerprint

Ribavirin
Chronic Hepatitis C
Safety
Hepacivirus
Genotype
Fibrosis
Pharmacokinetics
Therapeutics
Gastroenteritis
Abscess
Interferons
Abdominal Pain
Tablets
Area Under Curve
Headache
Tooth
Fever
Confidence Intervals

ASJC Scopus subject areas

  • Hepatology

Cite this

Murray, K. F., Balistreri, W. F., Bansal, S., Whitworth, S., Evans, H. M., Gonzalez-Peralta, R. P., ... Rosenthal, P. (2018). Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11. Hepatology, 68(6), 2158-2166. https://doi.org/10.1002/hep.30123

Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11. / Murray, Karen F.; Balistreri, William F.; Bansal, Sanjay; Whitworth, Suzanne; Evans, Helen M.; Gonzalez-Peralta, Regino P.; Wen, Jessica; Massetto, Benedetta; Kersey, Kathryn; Shao, Jiang; Garrison, Kimberly L.; Parhy, Bandita; Brainard, Diana M.; Arnon, Ronen; Gillis, Lynette A.; Jonas, Maureen M.; Lin, Chuan Hao; Narkewicz, Michael R.; Schwarz, Kathleen; Rosenthal, Philip.

In: Hepatology, Vol. 68, No. 6, 01.12.2018, p. 2158-2166.

Research output: Contribution to journalArticle

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 2018, 'Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11', Hepatology, vol. 68, no. 6, pp. 2158-2166. https://doi.org/10.1002/hep.30123
Murray KF, Balistreri WF, Bansal S, Whitworth S, Evans HM, Gonzalez-Peralta RP et al. Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11. Hepatology. 2018 Dec 1;68(6):2158-2166. https://doi.org/10.1002/hep.30123
Murray, Karen F. ; Balistreri, William F. ; Bansal, Sanjay ; Whitworth, Suzanne ; Evans, Helen M. ; Gonzalez-Peralta, Regino P. ; Wen, Jessica ; Massetto, Benedetta ; Kersey, Kathryn ; Shao, Jiang ; Garrison, Kimberly L. ; Parhy, Bandita ; Brainard, Diana M. ; Arnon, Ronen ; Gillis, Lynette A. ; Jonas, Maureen M. ; Lin, Chuan Hao ; Narkewicz, Michael R. ; Schwarz, Kathleen ; Rosenthal, Philip. / Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11. In: Hepatology. 2018 ; Vol. 68, No. 6. pp. 2158-2166.
@article{452ec88b7aca48f9932870bb9bdc8a1c,
title = "Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11",
abstract = "Currently, there are no interferon-free treatments available for hepatitis C virus (HCV)–infected patients younger than 12 years. We evaluated the safety and effectiveness of the all-oral regimen ledipasvir–sofosbuvir ± ribavirin in HCV-infected children aged 6 to <12 years. In an open-label study, patients aged 6 to <12 years received ledipasvir 45 mg–sofosbuvir 200 mg as two fixed-dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety-two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6-11). Most were perinatally infected (97{\%}) and treatment-naive (78{\%}). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99{\%} (91/92; 95{\%} confidence interval, 94{\%}-100{\%}). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration–time curve and maximum concentration values for sofosbuvir, its primary metabolite GS-331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50{\%}-200{\%}) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir–sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.",
author = "Murray, {Karen F.} and Balistreri, {William F.} and Sanjay Bansal and Suzanne Whitworth and Evans, {Helen M.} and Gonzalez-Peralta, {Regino P.} and Jessica Wen and Benedetta Massetto and Kathryn Kersey and Jiang Shao and Garrison, {Kimberly L.} and Bandita Parhy and Brainard, {Diana M.} and Ronen Arnon and Gillis, {Lynette A.} and Jonas, {Maureen M.} and Lin, {Chuan Hao} and Narkewicz, {Michael R.} and Kathleen Schwarz and Philip Rosenthal",
year = "2018",
month = "12",
day = "1",
doi = "10.1002/hep.30123",
language = "English (US)",
volume = "68",
pages = "2158--2166",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

TY - JOUR

T1 - Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11

AU - Murray, Karen F.

AU - Balistreri, William F.

AU - Bansal, Sanjay

AU - Whitworth, Suzanne

AU - Evans, Helen M.

AU - Gonzalez-Peralta, Regino P.

AU - Wen, Jessica

AU - Massetto, Benedetta

AU - Kersey, Kathryn

AU - Shao, Jiang

AU - Garrison, Kimberly L.

AU - Parhy, Bandita

AU - Brainard, Diana M.

AU - Arnon, Ronen

AU - Gillis, Lynette A.

AU - Jonas, Maureen M.

AU - Lin, Chuan Hao

AU - Narkewicz, Michael R.

AU - Schwarz, Kathleen

AU - Rosenthal, Philip

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Currently, there are no interferon-free treatments available for hepatitis C virus (HCV)–infected patients younger than 12 years. We evaluated the safety and effectiveness of the all-oral regimen ledipasvir–sofosbuvir ± ribavirin in HCV-infected children aged 6 to <12 years. In an open-label study, patients aged 6 to <12 years received ledipasvir 45 mg–sofosbuvir 200 mg as two fixed-dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety-two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6-11). Most were perinatally infected (97%) and treatment-naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%-100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration–time curve and maximum concentration values for sofosbuvir, its primary metabolite GS-331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%-200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir–sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.

AB - Currently, there are no interferon-free treatments available for hepatitis C virus (HCV)–infected patients younger than 12 years. We evaluated the safety and effectiveness of the all-oral regimen ledipasvir–sofosbuvir ± ribavirin in HCV-infected children aged 6 to <12 years. In an open-label study, patients aged 6 to <12 years received ledipasvir 45 mg–sofosbuvir 200 mg as two fixed-dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety-two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6-11). Most were perinatally infected (97%) and treatment-naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%-100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration–time curve and maximum concentration values for sofosbuvir, its primary metabolite GS-331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%-200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir–sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.

UR - http://www.scopus.com/inward/record.url?scp=85054658137&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054658137&partnerID=8YFLogxK

U2 - 10.1002/hep.30123

DO - 10.1002/hep.30123

M3 - Article

C2 - 30070726

AN - SCOPUS:85054658137

VL - 68

SP - 2158

EP - 2166

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 6

ER -