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

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

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.

Study Overview

• Status: Recruiting
• Conditions: HCV Infection; Beta Thalassemia Major
• Intervention / Treatment: Drug: Sofosbuvir and Ledipasvir

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 Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Manal H El-Sayed, M.D.; Phone Number: 002 01227461120; Email: manalhelsayed@yahoo.co.uk
• Study Contact Backup: Name: Fatma S Ebeid, M.D.; Phone Number: 002 01095569596; Email: dr.fatma_ebeid@yahoo.com

Study Locations

• Egypt
  • Cairo, Egypt
    • Recruiting
    • Masri-Crc
    • Contact: Manal H El-Sayed, M.D.; Phone Number: 002 01227461120; Email: manalhelsayed@yahoo.co.uk
    • Contact: Fatma S Ebeid, M.D.; Phone Number: 002 01095569596; Email: dr.fatma_ebeid@yahoo.com
    • Sub-Investigator: Eman A El-Baraky, Ms.C.
    • Sub-Investigator: Nirmeen A Sabry, Ph.D.
    • Principal Investigator: Maggie M Abbassi, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: Manal H El-Sayed, M.D, Director of MARSI-CRC

Publications and helpful links

General Publications

• El-Baraky IA, Abbassi MM, Ebeid FS, Hassany M, Sabry NA, El-Sayed MH. Beta-thalassemia major alters sofosbuvir/ledipasvir exposure in Hepatitis C virus infected adolescent patients. Clin Res Hepatol Gastroenterol. 2021 Sep;45(5):101747. doi: 10.1016/j.clinre.2021.101747. Epub 2021 Jun 26.

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2018
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: July 15, 2019
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Hepatitis C virus; Sofosbuvir; Ledipasvir; Pharmacokinetic Modeling; Direct acting antivirals; Beta thalassemia major
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Genetic Diseases, Inborn; Flaviviridae Infections; Hepatitis, Viral, Human; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Hepatitis; Hepatitis C; Hematologic Diseases; Thalassemia; beta-Thalassemia; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
• Other Study ID Numbers: CL30114

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No