Pharmacokinetics of Ledipasvir/Sofosbuvir in Hepatitis C Virus-Infected Children With Hematological Malignancy

This is a prospective, controlled, open-label, pharmacokinetic study. This study aims at studying the PK of ledipasvir, sofosbuvir, and GS-331007 metabolite in HCV infected children with hematological malignancy.

In this study, patients in both treatment groups will receive 12 weeks of treatment with a fixed-dose combination tablet containing 45 mg of ledipasvir and 200 mg of sofosbuvir (LDV/SOF) orally, once daily with food.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic; Hematologic Malignancy
• Intervention / Treatment: Drug: Ledipasvir / Sofosbuvir Oral Product

Detailed Description

In this study, patients in both treatment groups will receive 12 weeks of treatment with a fixed-dose combination tablet containing 45 mg of ledipasvir and 200 mg of sofosbuvir (LDV/SOF) orally, once daily with food, as prescribed by the attending physician.

Twelve eligible HCV-infected patients with hematological malignancy and 12 matching HCV control patients without haematological malignancy or co-morbidities 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, time on maintenance chemotherapy, 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 normalized ratio (INR), alpha fetoprotein (AFP), complete blood count (CBC), degree of liver fibrosis by Fibroscan, and viral load by PCR.

Followup will be done for all participants at baseline, after 12 weeks of treatment, and after 12 weeks from the end of treatment. A Forth visit will be done after 10 days of treatment for the evaluation of the steady state PK parameters of LDV\SOF in those patients.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Manal H ElSayed, MD; Phone Number: 01227461120; Email: manalhelsayed@yahoo.co.uk
• Study Contact Backup: Name: Fatma S Ebeid, MD; Phone Number: 01095569596; Email: dr.fatma_ebeid@yahoo.com

Study Locations

• Egypt
  • Cairo, Egypt, 11556
    • Pediatric Hematology Oncology and BMT Department, Faculty of Medicine, Ain Shams University
  • Al Qāhirah
    • Cairo, Al Qāhirah, Egypt, 11566
      • Faculty of Medicine Ain Shams Research Institute- Clinical Research Center (MASRI-CRC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children (6 to < 12 years of age and/or weighing 17.5 to < 35 Kg).
• Chronic HCV genotype 4 infection for at least 6 months without cirrhosis (confirmed by Fibroscan).
• Naïve patients to previous anti-HCV treatment.
• Diagnosed with hematological malignancy and on maintenance chemotherapy.

Exclusion Criteria:

• Known hypersensitivity to any of the study medications.
• Ongoing treatment with any interacting medications like carbamazepine, fosphenytoin, phenytoin, oxcarbazepine, phenobarbital, and rifampin.

• History of any comorbid illness that may interfere with the pharmacokinetics of the study drugs or prohibit the compliance with the study protocol such as;

  1. Decompensated liver disease as shown by the presence of ascites, encephalopathy, or a history of variceal hemorrhage.
  2. The ongoing treatment of other types of cancer or blood disorders.
  3. Co-infection with human immunodeficiency virus (HIV), or hepatitis B virus.
  4. Renal dysfunction.
  5. Active infection that is currently producing symptoms.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: HCV-infected patients with hematological malignancy; HCV-infected patients with hematological malignancy on maintenance chemotherapy	Drug: Ledipasvir / Sofosbuvir Oral Product; 45 mg of ledipasvir and 200 mg of sofosbuvir orally, once daily with food; Other Names: LDV\SOF
Active Comparator: Control HCV-infected patients; Control HCV-infected patients without haematological malignancy or co-morbidities.	Drug: Ledipasvir / Sofosbuvir Oral Product; 45 mg of ledipasvir and 200 mg of sofosbuvir orally, once daily with food; Other Names: LDV\SOF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of the pharmacokinetics of LDV\SOF	After 10 days of treatment, the steady state for LDV/SOF will be reached. Serial blood samples (2 mL/sample) will be collected at this time for the determination of LDV/SOF and GS-331007 concentrations from patients using an eight-point plasma schedule. Blood sampling schedule will be as follows (Predose, 0.5,1, 2, 3, 4, 8, and 12h post dose; with predose also serving as t = 24). Any deviations from nominal sampling times will be accurately recorded.	Blood samples will be collected after 10 days of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of the number of participants with sustained virological response (SVR12), 12 weeks after discontinuation of therapy with ledipasvir-sofosbuvir (LDV-SOF).	Number of Participants with sustained virological response at 12 Weeks after end of study drug treatment (SVR12) will be recorded. Participant will be considered to have achieved SVR12 if HCV RNA is less than the lower limit of quantification of <15 IU/ml) at 12 weeks after the end of treatment.	12 weeks after discontinuation of therapy with ledipasvir-sofosbuvir (LDV\SOF)

Collaborators and Investigators

• Sponsor: Ain Shams University
• Collaborators: Cairo University
• Investigators: Principal Investigator: Manal H Elsayed, MD, Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): July 1, 2023
• Study Completion (Actual): August 15, 2023

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: April 3, 2019
• First Posted (Actual): April 4, 2019

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 19, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pediatrics; Leukemia; Hepatitis C virus; Sofosbuvir; Ledipasvir; Antiviral Drugs; Pharmacokinetic Modeling
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Neoplasms by Site; Disease Attributes; Hematologic Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Chronic Disease; Neoplasms; Hematologic Neoplasms; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
• Other Study ID Numbers: CL 3062

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
• product manufactured in and exported from the U.S.: No