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

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.

Timeline

Start

2014-11-05

Primary completion

2018-06-15

Completion

2018-08-24

Publications

• Results 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
• Results 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
• Results 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
• Results 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
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• 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.

Drugs

Indications