NCT03487848

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

Terminated Phase 2 Results posted Last updated 20 April 2021

What this trial tests

Phase 2 trial testing Daclatasvir in Hepatitis C in 5 participants. Terminated before completion.

Timeline

25 June 2018

Primary endpoint
18 October 2018

17 September 2020

Quick facts

Lead sponsor	Bristol-Myers Squibb
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	5
Start date	25 June 2018
Primary completion	18 October 2018
Estimated completion	17 September 2020
Sites	2 locations across Australia, Spain

Drugs / interventions tested

• Daclatasvir (DACLATASVIR) — full drug profile →
• Sofosbuvir — full drug profile →

Conditions studied

• Hepatitis C — all drugs for Hepatitis C →
• Chronic Hepatitis — all drugs for Chronic Hepatitis →

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

Adults 12 to 17, any sex, with Hepatitis C or Chronic Hepatitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Minimum (Trough) Observed Plasma Concentration (Cmin) for Daclatasvir Primary · Day 10 after first dose, collection timepoints at pre-dose, 30 min, 1 hour, 2 hours, 4 hours, and 8 hours post-dose

Group	Value	95% CI
Daclatasvir (DCV) + Sofosbuvir (SOF)	152.94	± 48.3

Maximum Observed Plasma Concentration (Cmax) for Daclatasvir Primary · Day 10 after first dose, collection timepoints at pre-dose, 30 min, 1 hour, 2 hours, 4 hours, and 8 hours post-dose

Group	Value	95% CI
Daclatasvir (DCV) + Sofosbuvir (SOF)	1215.32	± 37.2

Time of Maximum Observed Plasma Concentration (Tmax) for Daclatasvir Primary · Day 10 after first dose, collection timepoints at pre-dose, 30 min, 1 hour, 2 hours, 4 hours, and 8 hours post-dose

Group	Value	95% CI
Daclatasvir (DCV) + Sofosbuvir (SOF)	2.00	1.0 – 4.0

Area Under the Concentration-Time Curve (AUC(TAU)) for Daclatasvir Primary · Day 10 after first dose, collection timepoints at pre-dose, 30 min, 1 hour, 2 hours, 4 hours, and 8 hours post-dose

Group	Value	95% CI
Daclatasvir (DCV) + Sofosbuvir (SOF)	11535.45	± 26.6

Apparent Total Body Clearance (CLT/F) for Daclatasvir Primary · Day 10 after first dose, collection timepoints at pre-dose, 30 min, 1 hour, 2 hours, 4 hours, and 8 hours post-dose

Group	Value	95% CI
Daclatasvir (DCV) + Sofosbuvir (SOF)	86.69	± 22.3

Number of Participants Experiencing Adverse Events Secondary · From first dose to last dose (12 weeks)

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

Adverse Events (AEs)

Group	Value	95% CI
Daclatasvir (DCV) + Sofosbuvir (SOF)	4

Serious Adverse Events (SAEs)

Group	Value	95% CI
Daclatasvir (DCV) + Sofosbuvir (SOF)	0

AEs leading to discontinuation

Group	Value	95% CI
Daclatasvir (DCV) + Sofosbuvir (SOF)	0

Number of Participants Experiencing Laboratory Abnormalities - On-treatment Analysis Secondary · 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 gr

Group	Value	95% CI
Daclatasvir (DCV) + Sofosbuvir (SOF)	1

Number of Participants Experiencing Laboratory Abnormalities - Follow-up Analysis Secondary · 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 gr

Group	Value	95% CI
Daclatasvir (DCV) + Sofosbuvir (SOF)	2

Percentage of Participants With Hepatitis C Virus (HCV) RNA Levels Below the Lower Limit of Quantitation (LLOQ) at Post-Treatment Follow-Up Week 12 Secondary · 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)

Group	Value	95% CI
Daclatasvir (DCV) + Sofosbuvir (SOF)	100	50 – 100

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose to 30 days following last dose. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Daclatasvir (DCV) + Sofosbuvir (SOF)

Serious: 0/5 (0%)

Deaths: 0/5

Other adverse events (10 terms — click to expand)

Reaction	System	Daclatasvir (DCV) + Sofosb…
Headache	Nervous system disorders	—
Abdominal pain	Gastrointestinal disorders	—
Pyrexia	General disorders	—
Seasonal allergy	Immune system disorders	—
Nasopharyngitis	Infections and infestations	—
Rhinitis	Infections and infestations	—
Upper respiratory tract infection	Infections and infestations	—
Limb injury	Injury, poisoning and procedural complications	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—

Data from ClinicalTrials.gov NCT03487848 adverse events section.

Sponsor's own description

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

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Review article: direct-acting antivirals for the treatment of HCV during pregnancy and lactation - implications for maternal dosing, foetal exposure, and safety for mother and child.
   Freriksen JJM, van Seyen M, Judd A, Gibb DM, et al · · 2019 · cited 33× · PMID 31448450 · DOI 10.1111/apt.15476
2. Hepatitis C virus infection in mothers and children.
   Greenaway E, Biondi MJ, Feld JJ, Ling SC. · · 2019 · cited 4× · PMID 35992762 · DOI 10.3138/canlivj.2019-0009
3. [Use of sofosbuvir-based regimens in the treatment of adolescents and children with chronic hepatitis C].
   He S, Wang XY, Han QY, Liu ZW. · · 2021 · PMID 33548971 · DOI 10.3760/cma.j.cn501113-20190606-00199