Clinical Pharmacokinetics of Daclatasvir/Sofosbuvir in Adolescents With Hepatitis C Virus

NCT03540212 | Unknown Phase 2 DMC

• 1 other identifier: FMASU P69a/2017
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is an interventional Phase II/III, single center, single arm clinical trial to assess the pharmacokinetics, efficacy, safety and tolerance of daclatasvir plus sofosbuvir in treatment-naïve, non-cirrhotic adolescents with chronic HCV GT-4 infection. A single-arm evaluation of daclatasvir/sofosbuvir will focus on the pharmacokinetics, efficacy and safety All enrolled patients will receive daclatasvir 60 mg orally once daily plus sofosbuvir at a dose of 400 mg orally once daily for 12 weeks.

Conditions

Chronic HCV Infection

Outcome Measures

Primary Outcomes (1)

• Measurement of the pharmacokinetics of DCV-SOF

  Blood samples (3 mL) will be collected to measure dactalasvir concentrations from pediatric patients using a nine-point plasma schedule (pre-dose, 0.5,1, 2, 4, 8, 12, and 24 h post-dose) on day 8 of therapy. (This will be a total of 27 mL/patient, which is well below the maximum allowed internationally recognized value of blood loss is 2.4mL/kg in a 4 month period. Any deviations from nominal sampling times should be recorded. AUCtau which is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval will be calculated

  Blood samples will be collected on day 8 of therapy

Secondary Outcomes (1)

• Measurement of Number of Participants With sustained virological response (SVR12), 12 weeks after discontinuation of therapy with daclatasvir-sofosbuvir (DCV-SOF).

  12 weeks after discontinuation of therapy with daclatasvir-sofosbuvir (DCV-SOF).

Study Arms (1)

Daclatasvir and sofosbuvir

EXPERIMENTAL

Daclatasvir and sofosbuvir Single arm intervention open label trial for single tablet (Daclatasvir 90 mg and Sofosbuvir 400mg and ) Daclatasvir 90 mg for 12 weeks

Drug: Daclatasvir and sofosbuvir

Interventions

Daclatasvir and sofosbuvir DRUG

Daclatasvir is a DAAs that can inhibit the HCV non-structural (NS) 5A protein when used in combination with other HCV-therapies. It has a linear, non-time-dependent pharmacokinetic profile and nanomolar potency in vitro against HCV genotypes 1-6. It is excreted primarily via faeces, about 88% in an unchanged form while renal excretion accounts for approximately 7% of its elimination. DOSE OF SOFOSBUVIR: 400 mg tablet orally once daily with food (in the morning) for 12 weeks for adolescents with liver fibrosis Metavir score F0-F2. DOSE OF DACLTASVIR: 60 mg tablet orally once daily with food (in the morning) for 12 weeks for adolescents with liver fibrosis Metavir score F0-F2.

Also known as: DCV-SOF, Sofosbuvir-Daclatasvir

Daclatasvir and sofosbuvir

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Adolescents (ages 12- 18 years) and/ or weight ≥ 35 kg
• HCV genotype 4 infected
• Naïve non-cirrhotic population with FIB Score: F0 to F3.
• Screening laboratory values within define thresholds
• Both sex
• Evidence of HCV infection determined by positive anti-HCV antibody and HCV RNA by polymerase chain reaction (PCR)
• HCV treatment-naïve
• Absolute neutrophil count ≥ 1,500/mm3
• Hemoglobin level ≥ 10 g/dL
• Platelets \> 75000 cells/mm3
• Albumin \> 3.5 mg/dL
• PT \< 3 sec above control and INR within accepted range
• Random glucose level within normal range
• Serum creatinine \< 1.5 mg/dL
• Biopsy is not required for study entry.

You may not qualify if:

• Previous treatment for HCV.
• History of clinically significant illness or any other medical condition that may interfere with individuals' treatment, assessment, or compliance with protocol.
• Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus
• Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage)
• Pregnant or nursing females
• Use of any illicit concomitant medications as within 28 days of the Day 1
• Renal dysfunction
• Ongoing treatment with Prohibited drugs.
• Chronic liver disease due to a cause other than HCV e.g. autoimmune disease, Wilson disease,…etc.
• Alfa-fetoprotein level \>50 ng/mL
• Serum creatinine \>1.5 mg/dL
• Simultaneous acute hepatitis A infection
• Known hypersensitivity to daclatasvir or sofosbuvir
• History of gastrointestinal disease or surgical procedure
• Blood /blood product transfusion within 4 weeks prior to study

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Pediatric Department, Faculty of Medicine, Ain Shams University

Cairo, Non-US, 11556, Egypt

RECRUITING

Related Publications (1)

• Al-Nahari MM, Abbassi MM, Ebeid FS, Hassany M, El-Sayed MH, Farid SF. Pharmacokinetics of daclatasvir in Egyptian adolescents with genotype-4 HCV infection. Antivir Ther. 2020;25(2):101-110. doi: 10.3851/IMP3357.

  PMID: 32367815 DERIVED

MeSH Terms

Interventions

daclatasvir; Sofosbuvir

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Officials

• Manal H El-Sayed, MD

  Professor of Pediatric, Faculty of Medicine, Ain Shams University, Egypt

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manal H El-Sayed, MD

CONTACT

00201227461120; manalhelsayed@yahoo.co.uk

Fatma SE Ebeid, MD

CONTACT

00201095569596; dr.fatma_ebeid@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: February 23, 2018
• First Posted: May 30, 2018
• Study Start: December 10, 2017
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2023
• Last Updated: March 6, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)