PK of SOF/LED in HCV - Infected Adolescents With Haematological Disorders

HCV Infection Clinical Trial

Official title:

Pharmacokinetics of Sofosbuvir and Ledipasvir in Hepatitis C Virus - Infected Adolescent Patients With Haematological Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04353986
• Other study ID #: CL30114
• Status: Recruiting
• Phase: Phase 3
• Start date: June 11, 2018
• Est. completion date: December 2023

Study information

• Verified date: March 2023
• Source: Ain Shams University
• Contact: Manal H El-Sayed, M.D.
• Phone: 01227461120
• Email: manalhelsayed[@]yahoo.co.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, controlled, open-label, pharmacokinetic study. This study aims at studying the PK of sofosbuvir, ledipasvir and sofosbuvir metabolite (GS-331007) in HCV infected children with hematological Disorders. to develop predictive pharmacokinetic model for the 3 moieties in the studied population. In this study, patients in both treatment groups will receive 12 weeks of treatment with a fixed-dose combination tablet containing 400 mg of sofosbuvir and 90 mg of ledipasvir(SOF/LED) orally, once daily with food.

Description:

In this study, patients in both treatment groups will receive 12 weeks of treatment with a fixed-dose combination tablet containing 400 mg of sofosbuvir and 90 mg of ledipasvir(SOF/LED) orally, once daily with food, as prescribed by the attending physician. Twelve eligible HCV-infected patients with hematological disorder and 12 matching HCV control patients without haematological disorder or comorbidities will be enrolled in the study. At baseline, careful history of the recruited patients including demographic characteristics (age, height, weight, and gender), comorbidities, medication history, familial history, social history, blood transfusion history, and baseline laboratory tests will be documented. The baseline laboratory tests will include renal function tests (serum creatinine), liver function tests (bilirubin, albumin, AST, and ALT), international normalised ratio (INR), alpha fetoprotein (AFP), complete blood count (CBC), degree of liver fibrosis by Fibroscan,viral load by PCR and HCV genotype Follow-up will be done for all participants at baseline, after 10 days of treatment for the evaluation of the steady state PK parameters of SOF/LED in those patients, after 12 weeks of treatment, and after 12 weeks from the end of treatment. For a total of 4 follow-up visits.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 18 Years

Eligibility

Inclusion Criteria:

Inclusion criteria:

• Adolescents (ages 12-18 years) and/ or weight more than 35 Kg
• Diagnosed with beta-thalassemia major and receiving regular blood transfusion
• spleenectomised
• Chronic HCV infection (defined as more than 6 months history of the disease)
• Naïve non-cirrhotic population with FIB Score: F0 to F3 as measured by Fibroscan
• Screening laboratory values of the beta-thalassemia group within the following thresholds (absolute neutrophil count > 1500/mm3, platelets > 7500 cells/mm3 , Serum creatinine < 1.2 mg/dl, creatinine clearance > 40 mL/min, albumin >3.5 gm/dl, and aspartate transaminase (AST) and alanine transaminase (ALT) level less than 5 fold of the normal limit). Control group should have normal biochemical profile.
• Assent of the patients and consent of their legal guardians are required

Exclusion Criteria:

• Previous treatment for HCV.
• History of clinically significant illness or any other medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol or affect the pharmacokinetics of the study drugs. Such as,
• Ongoing or untreated cancer including haematologic and hepatic cancers
• Co-infection with human immunodeficiency virus (HIV), acute hepatitis A virus or hepatitis B virus
• Clincal hepatic decompensation (i.e., ascites, encephalopathy or variceal haemorrhage)
• Renal dysfunction
• Active infection (any infection showing clinical manifestation at time of sampling)
• Known hypersensitivity to study medications
• Ongoing treatment with cyclosporine, rifampin, phenytoin, carbamazepine, phenobarbital, or amiodarone.

Related Conditions & MeSH terms

• Beta Thalassemia Major
• beta-Thalassemia
• HCV Infection
• Hematologic Diseases
• Hepatitis C
• Thalassemia

Intervention

Drug:
• Sofosbuvir and Ledipasvir
fixed dose tablet containing 400 mg sofosbuvir and 90 mg ledipasvir

Locations

Country	Name	City	State
Egypt	Masri-Crc	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Predictive Pharmacokinetic Model	serial blood samples will be withdrawn to measure the drug level develop a Predictive Pharmacokinetic Model for sofosbuvir, ledipasvir and GS 331007	10 days
Primary	sustained virologic response	sustained virologic response	6 months
Secondary	adverse drug reactions	record any adverse drug reactions experienced by the patients	3 months