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

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03487848
• Collaborator: (none)
• Enrollment: 5
• Locations: 2
• Arm: 1
• Actual Duration (Months): 26.8
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C; Chronic Hepatitis	Drug: Daclatasvir; Drug: Sofosbuvir	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jun 25, 2018
• Actual Primary Completion Date: Oct 18, 2018
• Actual Study Completion Date: Sep 17, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Daclatasvir with Sofosbuvir Specified dose on specified days for specified duration	Drug: Daclatasvir; Specified dose on specified days for specified duration; Drug: Sofosbuvir; Specified dose on specified days for specified duration

Outcome Measures

Primary Outcome Measures

1. 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]

2. 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]

3. 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]

4. 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]

5. 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

1. 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.

2. 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.

3. 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.

4. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Melbourne	Victoria	Australia	3052
2	Local Institution	Barcelona		Spain	08950

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Study Protocol - Dec 18, 2019
• Statistical Analysis Plan - Dec 24, 2019

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT03487848
• Other Study ID Numbers: AI444-423; 2017-003338-94
• First Posted: Apr 4, 2018
• Last Update Posted: Apr 20, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Sofosbuvir

Study Results

Participant Flow

Pre-assignment Detail	5 participants were enrolled and treated

Arm/Group Title	Daclatasvir (DCV) + Sofosbuvir (SOF)
Arm/Group Description	DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Period Title: Overall Study
STARTED	5
COMPLETED	4
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Daclatasvir (DCV) + Sofosbuvir (SOF)
Arm/Group Description	DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Overall Participants	5
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	13.6 (1.3)
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	0 0%
Unknown or Not Reported	5 100%
Race/Ethnicity, Customized (Number) [Number]
White	4 80%
Other	1 20%

Outcome Measures

1. Primary Outcome

Title	Minimum (Trough) Observed Plasma Concentration (Cmin) 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

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Daclatasvir (DCV) + Sofosbuvir (SOF)
Arm/Group Description	DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	152.94 (48.3)

2. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) 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

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Daclatasvir (DCV) + Sofosbuvir (SOF)
Arm/Group Description	DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1215.32 (37.2)

3. Primary Outcome

Title	Time of Maximum Observed Plasma Concentration (Tmax) 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

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Daclatasvir (DCV) + Sofosbuvir (SOF)
Arm/Group Description	DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Measure Participants	5
Median (Full Range) [Hours]	2.00

4. Primary Outcome

Title	Area Under the Concentration-Time Curve (AUC(TAU)) 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

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Daclatasvir (DCV) + Sofosbuvir (SOF)
Arm/Group Description	DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	11535.45 (26.6)

5. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Daclatasvir (DCV) + Sofosbuvir (SOF)
Arm/Group Description	DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [mL/min]	86.69 (22.3)

6. Secondary Outcome

Title	Number of Participants Experiencing Adverse Events
Description	This outcome describes the number of participants experiencing different types of any grade adverse events.
Time Frame	From first dose to last dose (12 weeks)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Daclatasvir (DCV) + Sofosbuvir (SOF)
Arm/Group Description	DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Measure Participants	5
Adverse Events (AEs)	4 80%
Serious Adverse Events (SAEs)	0 0%
AEs leading to discontinuation	0 0%

7. Secondary Outcome

Title	Number of Participants Experiencing Laboratory Abnormalities - On-treatment Analysis
Description	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.
Time Frame	From the day after first dose to last dose (approximately 12 weeks)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Daclatasvir (DCV) + Sofosbuvir (SOF)
Arm/Group Description	DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Measure Participants	5
Count of Participants [Participants]	1 20%

8. Secondary Outcome

Title	Number of Participants Experiencing Laboratory Abnormalities - Follow-up Analysis
Description	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.
Time Frame	From day after last dose to end of follow-up period (up to approximately 96 weeks)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Daclatasvir (DCV) + Sofosbuvir (SOF)
Arm/Group Description	DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Measure Participants	5
Count of Participants [Participants]	2 40%

9. Secondary Outcome

Title	Percentage of Participants With Hepatitis C Virus (HCV) RNA Levels Below the Lower Limit of Quantitation (LLOQ) at Post-Treatment Follow-Up Week 12
Description	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)
Time Frame	12 weeks after last dose

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Daclatasvir (DCV) + Sofosbuvir (SOF)
Arm/Group Description	DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Measure Participants	5
Number (95% Confidence Interval) [Percent of Participants]	100 2000%

Adverse Events

Time Frame	From first dose to 30 days following last dose
Arm/Group Title	Daclatasvir (DCV) + Sofosbuvir (SOF)
Arm/Group Description	DCV 60 mg QD + SOF 400 mg QD for 12 weeks
All Cause Mortality
	Daclatasvir (DCV) + Sofosbuvir (SOF)
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Serious Adverse Events
	Daclatasvir (DCV) + Sofosbuvir (SOF)
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Daclatasvir (DCV) + Sofosbuvir (SOF)
	Affected / at Risk (%)	# Events
Total	4/5 (80%)
Gastrointestinal disorders
Abdominal pain	1/5 (20%)
General disorders
Pyrexia	1/5 (20%)
Immune system disorders
Seasonal allergy	1/5 (20%)
Infections and infestations
Nasopharyngitis	1/5 (20%)
Rhinitis	1/5 (20%)
Upper respiratory tract infection	1/5 (20%)
Injury, poisoning and procedural complications
Limb injury	1/5 (20%)
Nervous system disorders
Headache	2/5 (40%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/5 (20%)
Oropharyngeal pain	1/5 (20%)

Limitations/Caveats

This study was terminated early by sponsor for reasons unrelated to safety.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.