Chronic Hepatitis C Treatment in Egyptian Children With Gaucher Disease.

Study Overview
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Brief Summary
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This prospective open label study is designed to screen all available Gaucher disease patients [either on enzyme replacement therapy (ERT) or not] for hepatitis C virus (HCV) infection. Furthermore to evaluate the safety and effectiveness of combined Sofosbuvir/Ledipasvir regimen given for 12 weeks in chronically infected patients aged 6-18 years.

Detailed Description
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This is a prospective open label study, all Gaucher disease pediatric patients (6-18 years), diagnosed at or referred to the HCV Egyptian treatment site, Mansoura University Children's Hospital Gastroenterology and hepatology unit, after positive HCV screen results by Anti HCV antibodies and confirmatory positive quantitative HCV polymerase chain reaction (PCR) are going to be enrolled. Study protocol had been approved by the Mansoura faculty of Medicine Institutional Review Board (IRB). Study design: In this prospective study, patients will receive ledipasvir-sofosbuvir fixed dose combination tablet (90 mg ledipasvir, 400 mg sofosbuvir) once daily for 12 weeks for those 12-18 years and half the dose (45 mg ledipasvir, 200 mg sofosbuvir) once daily for 12 weeks for those 6-11 years. After the period of treatment, follow up visit are arranged at 4, 12 and 24 weeks post-treatment. Methods: Every patient will be subjected to the following: A. History taking: time and route of acquisition, medications including previous antiviral therapy B. Comprehensive medical examination before study entry will be carried out for all participants and symptom-directed examination in every visit. C. In every visit, adverse events and concurrent medication will be reported for safety issue. D. Tanner staging for pubertal assessment will be done for all patients prior to enrollment then at the end of therapy and end of post-treatment follow up. E. Laboratory tests: All patients had positive (Anti-HCV Ab) and HCV-RNA PCR for more than 6 months. HCV-RNA will be measured Basal pretreatment at week 12 on treatment then at week 12, 24 post-treatment. Complete blood count (CBC),liver function tests (LFTs), international normalized ratio (INR), and serum creatinine will be done in the same time frame. Lab investigations are going to be done as a part of the routine work, using commercially available kits. F. Percutaneous liver biopsy: Histological examination of liver biopsy will be done for all patients when feasible (Hemoglobin more than 10gm/dl, Platlet count more than 100 x103/mm2, Prothrombin time (PT) less than 3 seconds prolongation) and agreed by the patients and legal guardians. Liver fibrosis and necroinflammatory injury are going to be reported by a single expert pathologist according to the Modified Knodell score by Ishak, in which inflammatory activity is graded from 0-18 and fibrosis is graded from 0-6. Alternatively transient hepatic elastography by fibroscan is going to be done for those patients with contraindication or refusing liver biopsy.

Official Title
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Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed Dose Combination Therapy in Treatment of Chronic Hepatitis C Infection in Egyptian Children With Gaucher Disease

Conditions
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Gaucher Disease, HCV

Intervention / Treatment
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* Drug: Ledipasvir/Sofosbuvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 6 to <18 years Parent or legal guardian must provide written informed consent Treatment naïve or experienced children with chronic HCV infection Chronic HCV infection (≥ 6 months) documented by medical history or liver biopsy Screening laboratory values within defined thresholds No History of solid organ or bone marrow transplantation No history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage) Exclusion Criteria: Patients with other sever comorbidities of chronic medical illness (e.g. decompensated heart disease, chronic kidney insufficiency) Concomitant hepatitis B virus (HBV) or Human immunodeficiency virus (HIV) infection Medications (systemic steroids, immunosuppressives) Patients or guardians who are unwilling to participate or sign informed consent

Ages Eligible for Study
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Minimum Age: 6 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Ledipasvir/sofosbuvir fixed dose combination tablet (90 mg ledipasvir, 400 mg sofosbuvir) once daily for 12 weeks for those 12-18 years, Wt 35 kg or more and half the dose (45 mg ledipasvir, 200 mg sofosbuvir) once daily for 12 weeks for those 6-11 years, Wt Less than 35 kg. | Drug: Ledipasvir/Sofosbuvir<br>* Direct acting anti HCV drugs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with Sustained Virologic Response | Proportion of patients achieving negative HCV PCR 12 weeks after therapy | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of HCV infection among Gaucher disease children | Number of HCV PCR positive Gaucher disease patients/Number of screened Gaucher Disease patients | 12 months | 
| Drug intolerability | Proportion of patients who permanently discontinue study drug due to an adverse event. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ledipasvir/Sofosbuvir, Gaucher disease, HCV