Health Condition 1: null- Adolescents and Children with Genotype 2 or 3 Chronic HCV Infection.
Conditions
Interventions
Intervention1: sofosbuvir plus Ribavirin: (Cohort 2) SOF 200 mg (2 X 100 mg tablets) will be administered orally
once daily along with RBV weight-based dosing
Treatment Phase â?? 12 or 24 weeks
Contr
Sponsors
Gilead Sciences Inc
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion criteria -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. -3 years to -PK Lead-in only: subjects in Cohort 1 (age 12 to -PK Lead-in only: subjects in Cohort 2 (age 6 to -PK Lead-in only: all subjects must be treatment naïve -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. -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 -Infection with HCV GT-2 or GT-3 as determined at Screening -HCV RNA >= 1000 IU/mL at Screening -Adequate hematologic function (absolute neutrophil count ï?³ 1,500/mm3; hemoglobin ï?³ 12 g/dL for males and ï?³ 11g/dL for females.) -Negative serum ï?¢-HCG pregnancy test (for females of childbearing potential only, as defined in Appendix 5) -Subject able to provide written assent, if they have the ability to read and write, as determined by IRB/IEC/local requirements and Investigatorâ??s discretion Exclusion criteria Pregnant or lactating subjects -Sexually-active males or females of childbearing potential who are not willing to use an effective method of contraception during the study -Decompensated liver disease defined as INR 1.2 ULN, platelets 50,000/mm3, serum albumin 3.5 g/dL, or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy, variceal hemorrhage) -Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilsonâ??s disease, alpha-1 antitrypsin deficiency) -Alfa fetoprotein 50 ng/mL -Serum creatinine > 1.5 mg/dL -Estimated glomerular filtration rate 90 mL/min/1.73m2, as calculated by the Schwartz Formula -Evidence of hepatocellular carcinoma (HCC) or other malignancy (with the exception of certain resolved skin cancers) -Co-infection with HIV, acute HAV, or HBV -Significant cardiovascular, pulmonary or neurological disease -Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications -History of solid organ or bone marrow transplantation -Chronic daily non-steroidal anti-inflammatory drug therapy -Systemic corticosteroid use for 5 days (pulmonary/nasal administration is permitted) -Investigational agents taken within the past 28 days (except with the expressed approval of the Sponsor) -Clinically-relevant alcohol or drug abuse within 12 months of screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator -Known hypersensitivity to the study drugs, the metabolites or formulation excipients -Any other condition (including alcohol or
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following exclusion criteria are not to be enrolled in this study. 1. Pregnant or lactating subjects 2. Sexually-active males or females of childbearing potential who are not willing to use an effective method of contraception during the study (see Appendix 5 for further details) 3. Decompensated liver disease defined as INR ï?¾ 1.2 ï?´ ULN, platelets ï?¼ 50,000/mm3, serum albumin ï?¼ 3.5 g/dL, or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy, variceal hemorrhage) 4. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilsonâ??s disease, alpha-1 antitrypsin deficiency) 5. ï?¡-fetoprotein ï?¾ 50 ng/mL 6. Serum creatinine > 1.5 mg/dL 7. Estimated glomerular filtration rate ï?¼ 90 mL/min/1.73m2, as calculated by the Schwartz Formula 8. Evidence of hepatocellular carcinoma (HCC) or other malignancy (with the exception of certain resolved skin cancers) 9. Co-infection with HIV, acute HAV, or HBV 10. Significant cardiovascular, pulmonary or neurological disease 11. Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications 12. History of solid organ or bone marrow transplantation 13. Chronic daily non-steroidal anti-inflammatory drug therapy 14. Systemic corticosteroid use for ï?³ 5 days (pulmonary/nasal administration is permitted) 15. Investigational agents taken within the past 28 days (except with the expressed approval of the Sponsor) 16. Clinically-relevant alcohol or drug abuse within 12 months of screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator 17. Known hypersensitivity to the study drugs, the metabolites or formulation excipients 18. Any other condition (including alcohol or substance abuse) or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements 19. Use of any prohibited concomitant medications as described in Section 5.6 within 28 days of the Day 1 visit. 20. Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years. Subjects with psychiatric illness (without the prior mentioned conditions) that is well-controlled on a stable treatment regimen for at least 12 months prior to enrollment or has not required medication in the last 12 months may be included
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of PK Lead-in Phase of this study is: â?¢ To evaluate the steady state pharmacokinetics (PK) and confirm the dose of SOF in HCV-infected paediatric subjects. The primary objective of Treatment Phase of this study is: â?¢ To evaluate the safety and tolerability of SOF + RBV for 12 or 24 weeks in HCV-infected paediatric subjects with GT-2 or GT-3, respectively Timepoint: week 12 and week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objective of PK Lead-in of this study is To evaluate the safety and tolerability of 7 days of dosing of SOF plus RBV in HCV-infected paediatric subjects. Timepoint: week 12 and week 24 | — |
Countries
Australia, Belgium, India, New Zealand, Russian Federation, United States of America
Contacts
Public ContactMr Pravin Moily
Klinera Corporation India
Outcome results
None listed