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

NCT ID: NCT03540212

Last Updated: 2023-03-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-10
• Study Completion Date: 2023-04-01

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).

Conditions

Chronic HCV Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Daclatasvir and sofosbuvir

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

Group Type: EXPERIMENTAL

Daclatasvir and sofosbuvir

Intervention Type: 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.

Interventions

Daclatasvir and sofosbuvir

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.

Intervention Type: DRUG

Other Intervention Names

DCV-SOF; Sofosbuvir-Daclatasvir

Eligibility Criteria

Inclusion Criteria

1. Adolescents (ages 12- 18 years) and/ or weight ≥ 35 kg

2. HCV genotype 4 infected

3. Naïve non-cirrhotic population with FIB Score: F0 to F3.

4. Screening laboratory values within define thresholds

5. Both sex

6. Evidence of HCV infection determined by positive anti-HCV antibody and HCV RNA by polymerase chain reaction (PCR)

7. HCV treatment-naïve

8. Absolute neutrophil count ≥ 1,500/mm3

9. Hemoglobin level ≥ 10 g/dL

10. Platelets > 75000 cells/mm3

11. Albumin > 3.5 mg/dL

12. PT < 3 sec above control and INR within accepted range

13. Random glucose level within normal range

14. Serum creatinine < 1.5 mg/dL

15. Biopsy is not required for study entry.

16. Signing informed consent by parents and patient assent

Exclusion Criteria

1. Previous treatment for HCV.

2. History of clinically significant illness or any other medical condition that may interfere with individuals' treatment, assessment, or compliance with protocol.

3. Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus

4. Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage)

5. Pregnant or nursing females

6. Use of any illicit concomitant medications as within 28 days of the Day 1

7. Renal dysfunction

8. Ongoing treatment with Prohibited drugs.

9. Chronic liver disease due to a cause other than HCV e.g. autoimmune disease, Wilson disease,…etc.

10. Alfa-fetoprotein level >50 ng/mL

11. Serum creatinine >1.5 mg/dL

12. Simultaneous acute hepatitis A infection

13. Known hypersensitivity to daclatasvir or sofosbuvir

14. History of gastrointestinal disease or surgical procedure

15. Blood /blood product transfusion within 4 weeks prior to study

16. Systemic corticosteroid use for more than 2 weeks (pulmonary/nasal administration was permitted)

17. Psychiatric hospitalization, suicide attempt or disability resulting from psychiatric illness within the prior 5 years

18. Clinically relevant alcohol or drug abuse within 12 months of screening

19. Ongoing treatment with any medications interacting with daclatasvir/sofosbuvir

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Manal Hamdy El-Sayed

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Manal H El-Sayed, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Pediatric Department, Faculty of Medicine, Ain Shams University

Cairo, Non-US, Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Manal H El-Sayed, MD

Role: CONTACT

manalhelsayed@yahoo.co.uk

00201227461120

Fatma SE Ebeid, MD

Role: CONTACT

dr.fatma_ebeid@yahoo.com

00201095569596

Facility Contacts

Manal H El-Sayed, MD

Role: primary

mamalhelsayed@yahoo.co.uk

00201227461120

Fatma Soliman E Ebeid, MD

Role: backup

dr.fatma_ebeid@yahoo.com

1095569596 ext. Ebeid

References

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.

Reference Type: DERIVED

PMID: 32367815 (View on PubMed)

Other Identifiers

FMASU P69a/2017

Identifier Type: -

Identifier Source: org_study_id