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

Primary Purpose

Chronic HCV Infection

Status

Recruiting

Phase

Phase 2

Locations

Egypt

Study Type

Interventional

Intervention

Daclatasvir and sofosbuvir

About this trial

This is an interventional treatment trial for Chronic HCV Infection

Eligibility Criteria

10 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
Signing informed consent by parents and patient assent

Exclusion Criteria:

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
Systemic corticosteroid use for more than 2 weeks (pulmonary/nasal administration was permitted)
Psychiatric hospitalization, suicide attempt or disability resulting from psychiatric illness within the prior 5 years
Clinically relevant alcohol or drug abuse within 12 months of screening
Ongoing treatment with any medications interacting with daclatasvir/sofosbuvir

Sites / Locations

Pediatric Department, Faculty of Medicine, Ain Shams UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Daclatasvir and sofosbuvir

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Number of Participants With sustained virological response at 12 Weeks after end of study drug treatment (SVR12) will be recorded, participant will be considered to have achieved SVR12 if HCV RNA is less than the lower limit of quantification of <15 IU/ml) at 12 weeks after the end of treatment.

Full Information

NCT ID

NCT03540212

First Posted

February 23, 2018

Last Updated

March 3, 2023

Sponsor

Ain Shams University

1. Study Identification

Unique Protocol Identification Number

NCT03540212

Brief Title

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

Official Title

Clinical Pharmacokinetics, Safety and Efficacy Study of Daclatasvir/Sofosbuvir in Adolescents Aged 12 to 18 Years Old With Hepatitis C Virus: A Preliminary Study

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 10, 2017 (Actual)

Primary Completion Date

April 1, 2023 (Anticipated)

Study Completion Date

April 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Ain Shams University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

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 efficacy, safety and pharmacokinetics, confirm the favorable pharmacological profile. 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. Patients will be followed closely for disease progression and any hypersensitivity or adverse reactions due to therapy. Laboratory values to be monitored at baseline: Serum creatinine, bilirubin, AST, ALT, HCV viral load (VL). Fifty patients will be included; the first twenty patients will be candidates for pharmacokinetic assessment. All patients (50), will be candidates for safety and efficacy assessment after verifying the PK results ''phase II''. Patients will be recruited at Ain Shams University hospitals, Egypt. The study will be conducted after approval of the corresponding research ethical committee and obtaining an informed consent from the parents/guardians and an assent from the patients. Patients will be requested to come for 2 screening visits, at the first day of therapy, weekly during the first four weeks, at the end of week 8 and week 12. Patients who will complete their treatment schedule will be scheduled for a visit after 12 weeks from end of therapy for assessment of sustained virological response (SVR). The total number of visits are 9. Duration of follow up will be 24 weeks from treatment initiation in addition to the screening period (2-4 weeks).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic HCV Infection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Daclatasvir and sofosbuvir

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Daclatasvir and sofosbuvir

Other Intervention Name(s)

DCV-SOF, Sofosbuvir-Daclatasvir

Intervention Description

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.

Primary Outcome Measure Information:

Title

Measurement of the pharmacokinetics of DCV-SOF

Description

Time Frame

Blood samples will be collected on day 8 of therapy

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

10 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Signing informed consent by parents and patient assent Exclusion Criteria: 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 Systemic corticosteroid use for more than 2 weeks (pulmonary/nasal administration was permitted) Psychiatric hospitalization, suicide attempt or disability resulting from psychiatric illness within the prior 5 years Clinically relevant alcohol or drug abuse within 12 months of screening Ongoing treatment with any medications interacting with daclatasvir/sofosbuvir

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Manal H El-Sayed, MD

Phone

00201227461120

manalhelsayed@yahoo.co.uk

First Name & Middle Initial & Last Name or Official Title & Degree

Fatma SE Ebeid, MD

Phone

00201095569596

dr.fatma_ebeid@yahoo.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Manal H El-Sayed, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

Pediatric Department, Faculty of Medicine, Ain Shams University

City

Cairo

State/Province

Non-US

ZIP/Postal Code

11556

Country

Egypt

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Manal H El-Sayed, MD

Phone

00201227461120

mamalhelsayed@yahoo.co.uk

First Name & Middle Initial & Last Name & Degree

Fatma Soliman E Ebeid, MD

Phone

1095569596

Ext

Ebeid

dr.fatma_ebeid@yahoo.com

First Name & Middle Initial & Last Name & Degree

Manal H El-Sayed, MD

First Name & Middle Initial & Last Name & Degree

Fatma SE Ebeid, MD

First Name & Middle Initial & Last Name & Degree

Aya M Kamal, MD

First Name & Middle Initial & Last Name & Degree

Mohamed Hassany, MD

First Name & Middle Initial & Last Name & Degree

Mogeb M Saif, MD

First Name & Middle Initial & Last Name & Degree

Samar F Farid

First Name & Middle Initial & Last Name & Degree

Maggie M Abbassi

First Name & Middle Initial & Last Name & Degree

Sara Makkeyah, MD

First Name & Middle Initial & Last Name & Degree

Mary Akhnokh, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32367815

Citation

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.

Results Reference

derived

Learn more about this trial

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

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