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

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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03487848

Enrollment

Registered

2018-04-04

Start date

2018-06-25

Completion date

2020-09-17

Last updated

2021-04-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Hepatitis, Hepatitis C

Brief summary

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

Interventions

DRUGDaclatasvir

Specified dose on specified days for specified duration

DRUGSofosbuvir

Specified dose on specified days for specified duration

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to 17 Years

Healthy volunteers

Inclusion criteria

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/

Design outcomes

Primary

Measure	Time frame
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
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

Secondary

Measure	Time frame	Description
Number of Participants Experiencing Laboratory Abnormalities - On-treatment Analysis	From the day after first dose to last dose (approximately 12 weeks)	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.
Number of Participants Experiencing Laboratory Abnormalities - Follow-up Analysis	From day after last dose to end of follow-up period (up to approximately 96 weeks)	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.
Percentage of Participants With Hepatitis C Virus (HCV) RNA Levels Below the Lower Limit of Quantitation (LLOQ) at Post-Treatment Follow-Up Week 12	12 weeks after last dose	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)
Number of Participants Experiencing Adverse Events	From first dose to last dose (12 weeks)	This outcome describes the number of participants experiencing different types of any grade adverse events.

Countries

Australia, Spain

Participant flow

Pre-assignment details

5 participants were enrolled and treated

Participants by arm

Arm	Count
Daclatasvir (DCV) + Sofosbuvir (SOF) DCV 60 mg QD + SOF 400 mg QD for 12 weeks	5
Total	5

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lost to Follow-up	1

Baseline characteristics

Characteristic	Daclatasvir (DCV) + Sofosbuvir (SOF)
Age, Continuous	13.6 Years STANDARD_DEVIATION 1.3
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants
Race/Ethnicity, Customized Other	1 Participants
Race/Ethnicity, Customized White	4 Participants
Sex: Female, Male Female	2 Participants
Sex: Female, Male Male	3 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 5
other Total, other adverse events	4 / 5
serious Total, serious adverse events	0 / 5

Outcome results

Primary

Apparent Total Body Clearance (CLT/F) for Daclatasvir

Time frame: Day 10 after first dose, collection timepoints at pre-dose, 30 min, 1 hour, 2 hours, 4 hours, and 8 hours post-dose