Ledipasvir-Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C

Kathleen Schwarz, Philip Rosenthal, Karen F. Murray, Jonathan R. Honegger, Winita Hardikar, Rosie Hague, Naveen Mittal, Benedetta Massetto, Diana M. Brainard, Chia Hsiang Hsueh, Jiang Shao, Bandita Parhy, Michael R. Narkewicz, Girish S. Rao, Suzanne Whitworth, Sanjay Bansal, William F. Balistreri

Research output: Contribution to journalArticle

Abstract

For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct-acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir-sofosbuvir in HCV-infected children aged 3 to <6 years. In an open-label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n = 33) or 4 (n = 1) received weight-based doses of combined ledipasvir-sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights ≥17 kg) for 12 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment naïve. No patients had known cirrhosis. Ten patients (29%) weighed <17 kg. SVR12 was achieved in 97% of patients (33 of 34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event “abnormal drug taste.” The most common adverse events were vomiting (24% of patients), cough (21%), and pyrexia (21%). No patients experienced a serious adverse event. Intensive pharmacokinetic analysis of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection.

Original languageEnglish (US)
JournalHepatology
DOIs
StateAccepted/In press - Jan 1 2019

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Chronic Hepatitis C
Hepacivirus
Virus Diseases
Weights and Measures
Therapeutics
Pharmacokinetics
sofosbuvir drug combination ledipasvir
Drug-Related Side Effects and Adverse Reactions
Cough
Vomiting
Antiviral Agents
Fibrosis
Fever
Genotype
Safety

ASJC Scopus subject areas

  • Hepatology

Cite this

Schwarz, K., Rosenthal, P., Murray, K. F., Honegger, J. R., Hardikar, W., Hague, R., ... Balistreri, W. F. (Accepted/In press). Ledipasvir-Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C. Hepatology. https://doi.org/10.1002/hep.30830

Ledipasvir-Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C. / Schwarz, Kathleen; Rosenthal, Philip; Murray, Karen F.; Honegger, Jonathan R.; Hardikar, Winita; Hague, Rosie; Mittal, Naveen; Massetto, Benedetta; Brainard, Diana M.; Hsueh, Chia Hsiang; Shao, Jiang; Parhy, Bandita; Narkewicz, Michael R.; Rao, Girish S.; Whitworth, Suzanne; Bansal, Sanjay; Balistreri, William F.

In: Hepatology, 01.01.2019.

Research output: Contribution to journalArticle

Schwarz, K, 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 2019, 'Ledipasvir-Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C', Hepatology. https://doi.org/10.1002/hep.30830
Schwarz, Kathleen ; Rosenthal, Philip ; Murray, Karen F. ; Honegger, Jonathan R. ; Hardikar, Winita ; Hague, Rosie ; Mittal, Naveen ; Massetto, Benedetta ; Brainard, Diana M. ; Hsueh, Chia Hsiang ; Shao, Jiang ; Parhy, Bandita ; Narkewicz, Michael R. ; Rao, Girish S. ; Whitworth, Suzanne ; Bansal, Sanjay ; Balistreri, William F. / Ledipasvir-Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C. In: Hepatology. 2019.
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abstract = "For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct-acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir-sofosbuvir in HCV-infected children aged 3 to <6 years. In an open-label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n = 33) or 4 (n = 1) received weight-based doses of combined ledipasvir-sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights ≥17 kg) for 12 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment na{\"i}ve. No patients had known cirrhosis. Ten patients (29{\%}) weighed <17 kg. SVR12 was achieved in 97{\%} of patients (33 of 34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event “abnormal drug taste.” The most common adverse events were vomiting (24{\%} of patients), cough (21{\%}), and pyrexia (21{\%}). No patients experienced a serious adverse event. Intensive pharmacokinetic analysis of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection.",
author = "Kathleen Schwarz and Philip Rosenthal and Murray, {Karen F.} and Honegger, {Jonathan R.} and Winita Hardikar and Rosie Hague and Naveen Mittal and Benedetta Massetto and Brainard, {Diana M.} and Hsueh, {Chia Hsiang} and Jiang Shao and Bandita Parhy and Narkewicz, {Michael R.} and Rao, {Girish S.} and Suzanne Whitworth and Sanjay Bansal and Balistreri, {William F.}",
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T1 - Ledipasvir-Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C

AU - Schwarz, Kathleen

AU - Rosenthal, Philip

AU - Murray, Karen F.

AU - Honegger, Jonathan R.

AU - Hardikar, Winita

AU - Hague, Rosie

AU - Mittal, Naveen

AU - Massetto, Benedetta

AU - Brainard, Diana M.

AU - Hsueh, Chia Hsiang

AU - Shao, Jiang

AU - Parhy, Bandita

AU - Narkewicz, Michael R.

AU - Rao, Girish S.

AU - Whitworth, Suzanne

AU - Bansal, Sanjay

AU - Balistreri, William F.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct-acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir-sofosbuvir in HCV-infected children aged 3 to <6 years. In an open-label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n = 33) or 4 (n = 1) received weight-based doses of combined ledipasvir-sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights ≥17 kg) for 12 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment naïve. No patients had known cirrhosis. Ten patients (29%) weighed <17 kg. SVR12 was achieved in 97% of patients (33 of 34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event “abnormal drug taste.” The most common adverse events were vomiting (24% of patients), cough (21%), and pyrexia (21%). No patients experienced a serious adverse event. Intensive pharmacokinetic analysis of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection.

AB - For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct-acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir-sofosbuvir in HCV-infected children aged 3 to <6 years. In an open-label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n = 33) or 4 (n = 1) received weight-based doses of combined ledipasvir-sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights ≥17 kg) for 12 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment naïve. No patients had known cirrhosis. Ten patients (29%) weighed <17 kg. SVR12 was achieved in 97% of patients (33 of 34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event “abnormal drug taste.” The most common adverse events were vomiting (24% of patients), cough (21%), and pyrexia (21%). No patients experienced a serious adverse event. Intensive pharmacokinetic analysis of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection.

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