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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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HCV Infection, Beta Thalassemia Major

Intervention / Treatment
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* Drug: Sofosbuvir and Ledipasvir


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a prospective, interventional, controlled, open-label, pharmacokinetic study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Beta thalassemia<br>HCV infected Beta thalassemia major adolescents | Drug: Sofosbuvir and Ledipasvir<br>* fixed dose tablet containing 400 mg sofosbuvir and 90 mg ledipasvir<br>* Other names: SOF/LED;|
| Active Comparator: Control<br>HCV infected, otherwise healthy, sex and age matched to the thalassemia group serving as control group | Drug: Sofosbuvir and Ledipasvir<br>* fixed dose tablet containing 400 mg sofosbuvir and 90 mg ledipasvir<br>* Other names: SOF/LED;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| sustained virologic response | sustained virologic response | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse drug reactions | record any adverse drug reactions experienced by the patients | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C virus, Pharmacokinetic Modeling, Pharmacokinetics, Sofosbuvir, Ledipasvir, Direct acting antivirals, Beta thalassemia major