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

N

National Liver Institute, Egypt

Status

Completed

Conditions

Hepatitis C, Chronic
Children, Only

Treatments

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

Study type

Interventional

Funder types

Other

Identifiers

NCT03764345
Sof-Led-HCV-Ped

Details and patient eligibility

About

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).

Full description

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.

Enrollment

30 patients

Sex

All

Ages

3 to 12 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

30 participants in 1 patient group

Sofosbovir/Ledipasvir Daily
Experimental group
Description:
Patients receive oral daily dose of Sofosbovir/Ledipasvir (200/45mg) daily for 8 weeks
Treatment:
Drug: Sofosbovir/Lepipasvir (200/45mg) tablet (Heterosofir)

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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