Evaluation of Daclatasvir (DCV) in Combination With Sofosbuvir (SOF) in Children With Chronic Hepatitis C (CHC) Infection

Study Overview
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Brief Summary
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The purpose of this study is to evaluate daclatasvir in combination with sofosbuvir given to children with chronic hepatitis C infection

Official Title
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Open-Label, Single-Arm Trial to Evaluate the Pharmacokinetics, Safety and Efficacy of Daclatasvir (DCV) in Combination With Sofosbuvir (SOF) in Children From 3 to Less Than 18 Years of Age With GT-1 to -6 Chronic Hepatitis C (CHC) Infection

Conditions
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Hepatitis C, Chronic Hepatitis

Intervention / Treatment
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* Drug: Daclatasvir
* Drug: Sofosbuvir


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Participants monoinfected with HCV genotype -1 to -6 HCV RNA ≥1,000 IU/mL at Screening Participants who are HCV-treatment naïve or treatment experienced Participants in Cohort 1 must have a body weight ≥ 45kg at Day 1 Exclusion Criteria: Mixed genotype HCV infections Evidence of an ongoing medical condition contributing to chronic liver disease other than HCV Evidence of cirrhosis, either compensated or decompensated Prior exposure to sofosbuvir and/or NS5A inhibitor Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daclatasvir with Sofosbuvir<br>Specified dose on specified days for specified duration | Drug: Daclatasvir<br>* Specified dose on specified days for specified duration<br>Drug: Sofosbuvir<br>* Specified dose on specified days for specified duration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimum (Trough) Observed Plasma Concentration (Cmin) for Daclatasvir |  | Day 10 after first dose, collection timepoints at pre-dose, 30 min, 1 hour, 2 hours, 4 hours, and 8 hours post-dose | 
| Maximum Observed Plasma Concentration (Cmax) for Daclatasvir |  | Day 10 after first dose, collection timepoints at pre-dose, 30 min, 1 hour, 2 hours, 4 hours, and 8 hours post-dose | 
| Time of Maximum Observed Plasma Concentration (Tmax) for Daclatasvir |  | Day 10 after first dose, collection timepoints at pre-dose, 30 min, 1 hour, 2 hours, 4 hours, and 8 hours post-dose | 
| Area Under the Concentration-Time Curve (AUC(TAU)) for Daclatasvir |  | Day 10 after first dose, collection timepoints at pre-dose, 30 min, 1 hour, 2 hours, 4 hours, and 8 hours post-dose | 
| Apparent Total Body Clearance (CLT/F) for Daclatasvir |  | Day 10 after first dose, collection timepoints at pre-dose, 30 min, 1 hour, 2 hours, 4 hours, and 8 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Adverse Events | This outcome describes the number of participants experiencing different types of any grade adverse events. | From first dose to last dose (12 weeks) | 
| Number of Participants Experiencing Laboratory Abnormalities - On-treatment Analysis | Laboratory tests abnormalities were analyzed in the following categories: Hematology (hemoglobin, platelets, international normalized ratio (INR), white blood cell count (WBC), lymphocytes (absolute), neutrophils + bands (absolute; ANC)). Hepatobiliary enzymes (ALT, AST, alkaline phosphatase, total bilirubin, albumin). Pancreatic enzymes (lipase, creatinine). Tests results were reported by worst toxicity grade (0 to 4) based on the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (2017). Only laboratory abnormalities with a worst toxicity grade 3 or higher in any of the above-mentioned tests, experienced during the on-treatment period, are reported here. | From the day after first dose to last dose (approximately 12 weeks) | 
| Number of Participants Experiencing Laboratory Abnormalities - Follow-up Analysis | Laboratory tests abnormalities were analyzed in the following categories: Hematology (hemoglobin, platelets, international normalized ratio (INR), white blood cell count (WBC), lymphocytes (absolute), neutrophils + bands (absolute; ANC)). Hepatobiliary enzymes (ALT, AST, alkaline phosphatase, total bilirubin, albumin). Pancreatic enzymes (lipase, creatinine). Tests results were reported by worst toxicity grade (0 to 4) based on the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (2017). Only laboratory abnormalities with a worst toxicity grade 3 or higher in any of the above-mentioned tests, experienced during the follow-up period, are reported here. | From day after last dose to end of follow-up period (up to approximately 96 weeks) | 
| Percentage of Participants With Hepatitis C Virus (HCV) RNA Levels Below the Lower Limit of Quantitation (LLOQ) at Post-Treatment Follow-Up Week 12 | HCV RNA levels were measured by using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test v2.0. This assay has a lower limit of quantitation (LLOQ) = 15 IU/mL. The outcome includes both results where Target was Detected (TD) but below LLOQ and results were Target was Not Detected (TND) | 12 weeks after last dose |