Clinical trial NCT02175758: Safety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children With Genotype 2 or 3 Chronic HCV Infection
Official title: A Phase 2, Open-Label, Multicenter, Multi-cohort, Single-Arm Study to Investigate the Safety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children With Genotype 2 or 3 Chronic HCV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C Virus Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-06-26
Enrollment: 106
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will have two parts as follows:

The PK Lead-in Phase of the study will evaluate the steady state pharmacokinetics (PK) and confirm the dose of sofosbuvir (SOF) in hepatitis C virus (HCV)-infected pediatric participants. The PK Lead-in Phase will also evaluate the safety and tolerability of 7 days of dosing of SOF+ribavirin (RBV) in HCV-infected pediatric participants.

The Treatment Phase will be initiated by age cohort after confirmation of age-appropriate SOF dosage levels. Participants from the PK Lead-in Phase will immediately rollover into the Treatment Phase with no interruption of study drug administration. The Treatment Phase will evaluate the antiviral efficacy, safety, and tolerability of SOF+RBV for 12 or 24 weeks in pediatric participants with genotype 2 or 3 HCV infection, respectively.


Eligibility criteria: Key Inclusion Criteria:

* Consent of parent or legal guardian required
* Chronic HCV infection genotype 2 or 3
* Screening laboratory values within defined thresholds
* PK Lead-in only: all individuals must be treatment naive

Key Exclusion Criteria:

* History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
* Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus
* Clinical hepatic decompensation (ie, 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF)
timeFrame: 6 to < 18 years of age: predose, 0.5, 1, 2, 3, 4, 8, and 12 hours postdose on Day 7; 3 to < 6 years of age: predose, 2, 4, 8, and 12 hours postdose on Day 7
measure: Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase or the Treatment Phase
timeFrame: Up to 24 weeks
measure: For the Treatment Phase, Percentage of Participants With SVR at 12 Weeks After Discontinuation of Therapy (SVR12)
timeFrame: Posttreatment Week 12
Secondary outcomes:
measure: For Participants in the PK Lead-in Phase, Change From Baseline in HCV RNA
timeFrame: Baseline; Weeks 1, 2, 4, 8, and 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)
measure: Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase
timeFrame: Up to Day 7
measure: For the Treatment Phase, Percentage of Participants With Sustained Virologic Response (SVR) at 4 Weeks After Discontinuation of Therapy (SVR4)
timeFrame: Posttreatment Week 4
measure: For the Treatment Phase, Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)
timeFrame: Posttreatment Week 24
measure: For the Treatment Phase, Percentage of Participants Experiencing Viral Breakthrough
timeFrame: Up to 24 weeks
measure: For the Treatment Phase, Percentage of Participants Experiencing Viral Relapse
timeFrame: Up to Posttreatment Week 24
measure: For the Treatment Phase, Change From Baseline in HCV RNA
timeFrame: Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)
measure: For the Treatment Phase, Percentage of Participants With HCV RNA < LLOQ While On Treatment
timeFrame: Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)
measure: For the Treatment Phase, Percentage of Participants With Alanine Aminotransferase (ALT) Normalization
timeFrame: Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Week 4
measure: For the Treatment Phase, Change From Baseline in Height
timeFrame: Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Weeks 4, 12, and 24
measure: For the Treatment Phase, Change From Baseline in Weight
timeFrame: Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Weeks 4, 12, and 24
measure: For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Pubic Hair
timeFrame: Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
measure: For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Genitalia Development
timeFrame: Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
measure: For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Pubic Hair
timeFrame: Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
measure: For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Breast Development
timeFrame: Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
measure: For the Treatment Phase, Palatability of SOF Granules at Day 1 as Assessed by the Percentage of Participants Able/Unable to Taste the SOF Oral Granules
timeFrame: Day 1
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Gainesville
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Indianapolis
country: United States
state: Indiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: New York
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Morgantown
country: United States
state: West Virginia
city: Westmead
country: Australia
state: New South Wales
city: Melbourne
country: Australia
state: Victoria
city: New Lambton Heights
country: Australia
city: Brussels
country: Belgium
city: Wuppertal
country: Germany
state: Nordrhein-westfalen
city: Berlin
country: Germany
city: Bologna
country: Italy
city: Firenze
country: Italy
city: Milano
country: Italy
city: Padova
country: Italy
city: San Giovanni Rotondo
country: Italy
city: Torino
country: Italy
city: Auckland
country: New Zealand
city: Moscow
country: Russian Federation
city: Novokuznetsk
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Tolyatti
country: Russian Federation
city: Birmingham
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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 [Poster 1707]. American Association for the Study of Liver Diseases (AASLD); 2015 November 13-17, San Francisco, USA. Hepatology 2015;62 (S1): 1040A-1041A
citation: 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 [Poster 878]. American Association for the Study of Liver Diseases (AASLD); 2016 11-15 November; Boston, MA. Hepatology 2016;64 (S1): 436A
citation: Schwarz KB, Rosenthal P, Gonzales-Peralta RP, Jonas MM, Balistreri WF, Lin CH, et al. Sofosbuvir + Ribavirin for 12 or 24 Weeks Is Safe and Effective in Adolescents with Genotype 2 or Genotype 3 Chronic Hepatitis C Infection. Hepatology 2016; 63 (Suppl 1): abstract 706.
citation: Wirth S, Rosenthal P, Gonzalez-Peralta RP, Jonas MM, Balistreri WF, Lin CH, Hardikar W, Kersey K, Massetto B, Kanwar B, Brainard DM, Shao J, Svarovskaia E, Kirby B, Arnon R, Murray KF, Schwarz KB. Sofosbuvir and ribavirin in adolescents 12-17 years old with hepatitis C virus genotype 2 or 3 infection. Hepatology. 2017 Oct;66(4):1102-1110. doi: 10.1002/hep.29278. Epub 2017 Aug 26.
citation: Younossi ZM, Stepanova M, Schwarz KB, Wirth S, Rosenthal P, Gonzalez-Peralta R, Murray K, Henry L, Hunt S. Quality of life in adolescents with hepatitis C treated with sofosbuvir and ribavirin. J Viral Hepat. 2018 Apr;25(4):354-362. doi: 10.1111/jvh.12830. Epub 2017 Dec 26.
citation: Rosenthal P, Schwarz KB, Gonzales-Peralta RP, Lin CH, Kelly DA, Nightingale S, et al. Sofosbuvir + Ribavirin for 12 or 24 Weeks Is Safe and Effective in Children 3 to <12 Years Old with Genotype 2 or Genotype 3 Chronic Hepatitis C Infection. Hepatology 2018; 68 (Suppl 1): abstract 1844.
citation: Rosenthal P, Schwarz KB, Gonzalez-Peralta RP, Lin CH, Kelly DA, Nightingale S, Balistreri WF, Bansal S, Jonas MM, Massetto B, Brainard DM, Hsueh CH, Shao J, Parhy B, Davison S, Feiterna-Sperling C, Gillis LA, Indolfi G, Sokal EM, Murray KF, Wirth S. Sofosbuvir and Ribavirin Therapy for Children Aged 3 to <12 Years With Hepatitis C Virus Genotype 2 or 3 Infection. Hepatology. 2020 Jan;71(1):31-43. doi: 10.1002/hep.30821. Epub 2019 Aug 13.