Trial Outcomes & Findings for Evaluation of Daclatasvir (DCV) in Combination With Sofosbuvir (SOF) in Children With Chronic Hepatitis C (CHC) Infection (NCT NCT03487848)

NCT ID: NCT03487848

Last Updated: 2021-04-20

Results Overview

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 5 participants
• Primary outcome timeframe: Day 10 after first dose, collection timepoints at pre-dose, 30 min, 1 hour, 2 hours, 4 hours, and 8 hours post-dose
• Results posted on: 2021-04-20

Participant Flow

5 participants were enrolled and treated

Participant milestones

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Overall Study STARTED	5
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Overall Study Lost to Follow-up	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) n=5 Participants DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Age, Continuous	13.6 Years STANDARD_DEVIATION 1.3 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Race/Ethnicity, Customized White	4 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants

PRIMARY outcome

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

Population: All treated participants

Outcome measures

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) n=5 Participants DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Minimum (Trough) Observed Plasma Concentration (Cmin) for Daclatasvir	152.94 ng/mL Geometric Coefficient of Variation 48.3

PRIMARY outcome

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

Population: All treated participants

Outcome measures

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) n=5 Participants DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Maximum Observed Plasma Concentration (Cmax) for Daclatasvir	1215.32 ng/mL Geometric Coefficient of Variation 37.2

PRIMARY outcome

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

Population: All treated participants

Outcome measures

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) n=5 Participants DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Time of Maximum Observed Plasma Concentration (Tmax) for Daclatasvir	2.00 Hours Interval 1.0 to 4.0

PRIMARY outcome

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

Population: All treated participants

Outcome measures

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) n=5 Participants DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Area Under the Concentration-Time Curve (AUC(TAU)) for Daclatasvir	11535.45 h*ng/mL Geometric Coefficient of Variation 26.6

PRIMARY outcome

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

Population: All treated participants

Outcome measures

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) n=5 Participants DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Apparent Total Body Clearance (CLT/F) for Daclatasvir	86.69 mL/min Geometric Coefficient of Variation 22.3

SECONDARY outcome

Timeframe: From first dose to last dose (12 weeks)

Population: All treated participants

This outcome describes the number of participants experiencing different types of any grade adverse events.

Outcome measures

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) n=5 Participants DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Number of Participants Experiencing Adverse Events Serious Adverse Events (SAEs)	0 Participants
Number of Participants Experiencing Adverse Events AEs leading to discontinuation	0 Participants
Number of Participants Experiencing Adverse Events Adverse Events (AEs)	4 Participants

SECONDARY outcome

Timeframe: From the day after first dose to last dose (approximately 12 weeks)

Population: All treated participants

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.

Outcome measures

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) n=5 Participants DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Number of Participants Experiencing Laboratory Abnormalities - On-treatment Analysis	1 Participants

SECONDARY outcome

Timeframe: From day after last dose to end of follow-up period (up to approximately 96 weeks)

Population: All treated participants

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.

Outcome measures

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) n=5 Participants DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Number of Participants Experiencing Laboratory Abnormalities - Follow-up Analysis	2 Participants

SECONDARY outcome

Timeframe: 12 weeks after last dose

Population: All treated participants

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)

Outcome measures

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) n=5 Participants DCV 60 mg QD + SOF 400 mg QD for 12 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	100 Percent of Participants Interval 50.0 to 100.0

Adverse Events

Daclatasvir (DCV) + Sofosbuvir (SOF)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Daclatasvir (DCV) + Sofosbuvir (SOF) n=5 participants at risk DCV 60 mg QD + SOF 400 mg QD for 12 weeks
Gastrointestinal disorders Abdominal pain	20.0% 1/5 • From first dose to 30 days following last dose
General disorders Pyrexia	20.0% 1/5 • From first dose to 30 days following last dose
Immune system disorders Seasonal allergy	20.0% 1/5 • From first dose to 30 days following last dose
Infections and infestations Nasopharyngitis	20.0% 1/5 • From first dose to 30 days following last dose
Infections and infestations Rhinitis	20.0% 1/5 • From first dose to 30 days following last dose
Infections and infestations Upper respiratory tract infection	20.0% 1/5 • From first dose to 30 days following last dose
Injury, poisoning and procedural complications Limb injury	20.0% 1/5 • From first dose to 30 days following last dose
Nervous system disorders Headache	40.0% 2/5 • From first dose to 30 days following last dose
Respiratory, thoracic and mediastinal disorders Epistaxis	20.0% 1/5 • From first dose to 30 days following last dose
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	20.0% 1/5 • From first dose to 30 days following last dose

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER