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 (Protocol GS-US-334-1112)
- Children’s Medical Center (Dallas, Plano, Southlake)
Norberto Rodriguez-Baez, M.D.
The study will be divided into 2 parts as follows:
PK Lead-in: Will evaluate and/or confirm age appropriate SoF
doses by analyzing PK, safety, and antiviral activity of SoF
administered in combination with RBV through 7 days of dosing
for each of three cohorts. Children aged 3 [Less Than] 6, children aged 6 to
[Less Than] 12 years and adolescents aged 12 to [Less Than] 18 years with genotype
GT-2 or GT-3 HCV infection and evidence of HCV Rna
[GreaterThanorequalTo] 1000 iu/mL at study entry will be evaluated. Subjects must be
treatment naive to participate in the PK Lead-in Phase.
Three cohorts of up to 10 subjects each will be sequentially
enrolled: - Cohort 1: 12 to [Less Than] 18 years old weighing [GreaterThanorequalTo] 45kg - Cohort 2: 6 to [Less Than] 12 years old - Cohort 3: 3 to [Less Than] 6 years old
The study will start with Cohort 1. Subjects will receive SoF
(400 mg adult tablet or 4 x 100 mg tablets if determined necessary
based on SoF swallowability assessment) + RBV for 7 days with
intensive PK conducted on Day 7.
PK Lead-in subjects in each cohort (Cohorts 1, 2 and 3) will
immediately enroll in the Treatment Phase as they complete Day 7
of the PK Lead-in Phase. They will continue dosing with SoF +
RBV with no interruption of study drug administration.
Following completion of study treatment in the PK Lead-in of each
Cohort, intensive PK and safety results will be reviewed to confirm
the appropriateness of the evaluated SoF dose for the Treatment
Phase of that Cohort as well as to determine the age-appropriate
dose to be evaluated in the PK Lead-in of the next Cohort.
Treatment Phase: Will be initiated sequentially by cohort after
confirmation of age-appropriate SoF dosage levels. Subjects who
participated in PK Lead-in Phase will immediately rollover into
Treatment Phase with no interruption of study drug administration
until the appropriateness of the dose is confirmed by PK and safety
data from the PK-Lead-in. These subjects will start at the Week 2
visit of the Treatment Phase. additional subjects will be enrolled in
the Treatment Phase of each Cohort upon confirmation of the
appropriateness of the dose.
Children aged 3 to [Less Than] 12 years and adolescents aged 12 to
[Less Than] 18 years with GT-2 or GT-3 infection and evidence of HCV
Rna [GreaterThanorequalTo] 1000 iu/mL at study entry (those who were dosed in the
PK Lead-in Phase will have met this criteria prior to enrollment)
will be evaluated.
Subjects enrolled in the study will receive the following regimen: - GT-2 subjects: SoF + RBV for 12 weeks - GT-3 subjects: SoF + RBV for 24 weeks
The study will enroll both treatment-naive and
treatment-experienced pediatric subjects, with up to 20 subjects
allowed to be treatment experienced. approximately 100 total
subjects, including subjects that participate in the PK Lead-in
Phase, will be enrolled in Treatment Phase as follows
- Group 1: approximately 50 adolescent subjects (12 to
[Less Than] 18 years of age) - Group 2: approximately 50 pediatric subjects (3 to [Less Than] 12 years
The study schedule contains the following visits: Screening, Day 1,
Weeks 1, 2, 4, 8, 12 (and Weeks 16, 20, and 24 for GT-3) during
the treatment phase followed by post-treatment visits 4, 12 and
24 weeks after discontinuation of therapy.
all subjects (those who attain SVR24 or those who do not attain SVR24) who do not initiate experimental or approved anti-HCV therapy will be followed every 6 months for assessments of growth, quality of life, and long term viral suppression (if applicable) in a separate protocol (GS-uS-334-1113). This follow-up will continue for 5 years.
Subjects must meet all of the following inclusion criteria to be eligible for participation in this
1. Parent or legal guardian able to provide written informed consent prior to any screening evaluations and willing to comply with study requirements. Subjects will provide assent if possible.
2. 3 years to < 18 years of age (consent of parent or legal guardian required)
3. PK Lead-in only: subjects in Cohort 1 (age 12 to <18 years of age) must weigh greater than or equal to 45 kg
4. PK Lead-in only: subjects in Cohort 2 (age 6 to <12 years of age) must weigh greater than or equal to 17 kg and < 45 kg
5. PK Lead-in only: all subjects must be treatment naive
6. Treatment experienced subjects: prior treatment failure to a regimen including interferon
either with or without RBV that was completed at least 8 weeks prior to Baseline/Day 1.
7. Chronic HCV infection documented by either:
a) a positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Day 1 visit, or
b) a liver biopsy performed prior to the Day 1 visit with evidence of chronic HCV infection
8. Infection with HCV GT-2 or GT-3 as determined at Screening
9. HCV RNA >= 1000 IU/mL at Screening
10. Adequate hematologic function (absolute neutrophil count greater than or equal to 1,500/mm3; hemoglobin greater tha of equal to12 g/dL for males and >=greater than or equal to 11g/dL for females.)
11. Negative serum beta-HCG pregnancy test (for females of childbearing potential only, as defined
in Appendix 5)
12. Subject able to provide written assent, if they have the ability to read and write, as determined by IRB/IEC/local requirements and Investigator[Right Quote]s discretion