Eight Weeks Sofosbovir/Ledipasvir in HCV Infected Children Aged 4 to 10 Years

Study Overview
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Brief Summary
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Recently the era of direct-acting antiviral drugs for hepatitis C treatment has changed the world map of HCV. Results in adults are promising. FDA approved only two drugs in the pediatric age group 12 to 17 years. Younger children are still on the wait list for treatment. The current study aimed to treat children aged between 3 and 12 years with half the adult dose of Sofosbuvir/Ledipasvir combination (Heterosofir).

Detailed Description
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The WHO has declared hepatitis C a global health problem, with ∼ 3% of the world's population (roughly 170-200 million individuals) infected with HCV. Egypt has the highest prevalence of HCV in the world, ranging from 6 to 28%, with an average of ∼ 13.8% in the general population. Ap-proximately 90% of Egyptian HCV isolates belong to a single subtype, 4a. Hepatitis C virus (HCV) is a major cause of chronic liver disease and a prin-cipal reason for liver transplant; approximately 170 million people worldwide are chronically infected. There is general consensus that HCV elimination is associated with strong and sustained CD4+ and CD8+ T cell res-ponses that target multiple epitopes within the different HCV proteins, however, they are not maintained in patients who develop chronic disease . A variety of factors purportedly contribute to the dimi-nished T cell responses observed in chronically infected patients, including an im-paired dendritic cell (DC) function. The successful development of direct-acting antivirals (DAAs) that are active against hepatitis C virus has transformed chronic hepatitis C infection from a con-dition requiring complex therapies with unsatisfactory outcomes to one that can be easily treated with few contraindications and side-effects. Since 2011, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved eight oral DAA regimens for the treatment of adults with chronic hepatitis C. Investigation into DAAs for children has been slower. For adolescents aged 12-17 years, the safety and efficacy of the fixed-dose combination sofosbuvir and ledipasvir for genotype 1 or 4 infection and of combination sofosbuvir plus ribavirin for genotype 2 or 3 infection have been described in full-length articles. A recent study explored the safety and efficacy of combination sofosbuvirplus ribavirin in Pakistani children (aged 5-18 years) with hepatitis C virus genotype 1, 2, or 3 infection. Further results have been presented as ab-stracts for the fixed-dose combination sofosbuvir and ledipasvir in children aged 6-11 years for the fixed-dose combination ombitasvir, pari-taprevir, and ritonavir with or without dasabuvir and with or without ribavirin in adolescents aged 12-17 years with genotype 1 or 4 infection and for combination sofosbuvir plus daclatasvir with or without ribavirin in Egyp-tian adolescents aged 12-17 years with genotype 4 infection. Dendritic cells are professional antigen presenting cells characterized by a po-tent capacity to elicit primary T cell responses. Two major subsets of DC can be identified from human peripheral blood: plasmacytoid (p) DC and conventional or myeloid (m) DC. Each subset represents 0.3-0.5% of the normal human peripheral blood mononuclear cell (PBMC) population.

Official Title
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Sofosbovir/Ledipasvir in HCV Infected Children Aged From 4 to 10 Years

Conditions
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Hepatitis C, Chronic, Children, Only

Intervention / Treatment
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* Drug: Sofosbovir/Lepipasvir (200/45mg) tablet (Heterosofir)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with chronic HCV age 3- 12 y old weight 17- 35kg Basal HCV viremia less than 6.8 log IU/mL Treatment-naive No cirrhosis Exclusion Criteria: Patients with dual HBV and HCV infection or associated with chronic hepatitis other than chronic HCV age below 3 years or above 12 years body weight less than 17 or more than 35 Kg HCV/HIV coinfection. Patients with HCV infection and HCC. Patients with HCV infection and underlying cardiac comorbidities Decompensated patients with HCV Hypoalbuminemia of < 3.5g/dL. International normalised ratio (INR) >2. Advanced fibrosis scoring by transient elastography (F 4 broScan) Any concomitant malignancy. Parents' refusal for participation of their children in the study.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 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: Sofosbovir/Ledipasvir Daily<br>Patients receive oral daily dose of Sofosbovir/Ledipasvir (200/45mg) daily for 8 weeks | Drug: Sofosbovir/Lepipasvir (200/45mg) tablet (Heterosofir)<br>* Patients receive oral daily dose of Sofosbovir/Ledipasvir (200/45mg) daily for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side effect 1 Number of patients with fatigue | Number of patients with fatigue | 8 weeks | 
| Side effect 2 Number of patients with Headache | Number of patients with Headache | 8 weeks | 
| Side effect 3 Number of patients with nausea | Number of patients with nausea | 8 weeks | 
| Side effect 4 Number of patients with diarrhea | Number of patients with diarrhea | 8 weeks | 
| Side effect 5 Number of patients with insomnia | Number of patients with insomnia | 8 weeks | 
| Side effect 6 Number of patients with weakness | Number of patients with weakness | 8 weeks | 
| Side effect 7 Number of patients with bradycardia | Number of patients with bradycardia | 8 weeks | 
| Side effect 8 Number of patients with cough | Number of patients with cough | 8 weeks | 
| Side effect 9 Number of patients with myalgia | Number of patients with myalgia | 8 weeks | 
| Side effect 10 Number of patients with dysapnea | Number of patients with dysapnea | 8 weeks | 
| Side effect 11 Number of patients with irritability | Number of patients with irritability | 8 weeks | 
| Side effect 12 Number of patients with dizziness | Number of patients with dizziness | 8 weeks | 
| Side effect 13 Number of patients with depression | Number of patients with depression | 8 weeks | 
| Side effect 14 Number of patients with skin rash | Number of patients with skin rash | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCV-RNA PCR by the end of therapy | HCV-RNA PCR at week 8 | 8 weeks | 
| HCV-RNA PCR after 20 weeks for SVR | HCV-RNA PCR at week 20 | 20 weeks |