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

Sponsor

Ain Shams University (Other)

Overall Status

Unknown status

CT.gov ID

NCT04353986

Collaborator

(none)

Enrollment

Location

Arms

29.7

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
HCV Infection Beta Thalassemia Major	Drug: Sofosbuvir and Ledipasvir	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a prospective, interventional, controlled, open-label, pharmacokinetic study.This is a prospective, interventional, controlled, open-label, pharmacokinetic study.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 11, 2018

Anticipated Primary Completion Date :

Apr 1, 2020

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Beta thalassemia HCV infected Beta thalassemia major adolescents	Drug: Sofosbuvir and Ledipasvir fixed dose tablet containing 400 mg sofosbuvir and 90 mg ledipasvir Other Names: SOF/LED
Active Comparator: Control HCV infected, otherwise healthy, sex and age matched to the thalassemia group serving as control group	Drug: Sofosbuvir and Ledipasvir fixed dose tablet containing 400 mg sofosbuvir and 90 mg ledipasvir Other Names: SOF/LED

Arm

Intervention/Treatment

Experimental: Beta thalassemia

HCV infected Beta thalassemia major adolescents

Drug: Sofosbuvir and Ledipasvir

fixed dose tablet containing 400 mg sofosbuvir and 90 mg ledipasvir

Other Names:

SOF/LED

Active Comparator: Control

HCV infected, otherwise healthy, sex and age matched to the thalassemia group serving as control group

Drug: Sofosbuvir and Ledipasvir

fixed dose tablet containing 400 mg sofosbuvir and 90 mg ledipasvir

Other Names:

SOF/LED

Outcome Measures

Primary Outcome Measures

Predictive Pharmacokinetic Model [10 days]
serial blood samples will be withdrawn to measure the drug level develop a Predictive Pharmacokinetic Model for sofosbuvir, ledipasvir and GS 331007
sustained virologic response [6 months]
sustained virologic response

Secondary Outcome Measures

adverse drug reactions [3 months]
record any adverse drug reactions experienced by the patients

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.