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

NCT ID: NCT03903185

Last Updated: 2023-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-01
• Study Completion Date: 2023-08-15

Brief Summary

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.

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.

Conditions

Hepatitis C, Chronic; Hematologic Malignancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HCV-infected patients with hematological malignancy

HCV-infected patients with hematological malignancy on maintenance chemotherapy

Group Type: ACTIVE_COMPARATOR

Ledipasvir / Sofosbuvir Oral Product

Intervention Type: DRUG

45 mg of ledipasvir and 200 mg of sofosbuvir orally, once daily with food

Control HCV-infected patients

Control HCV-infected patients without haematological malignancy or co-morbidities.

Group Type: ACTIVE_COMPARATOR

Ledipasvir / Sofosbuvir Oral Product

Intervention Type: DRUG

45 mg of ledipasvir and 200 mg of sofosbuvir orally, once daily with food

Interventions

Ledipasvir / Sofosbuvir Oral Product

45 mg of ledipasvir and 200 mg of sofosbuvir orally, once daily with food

Intervention Type: DRUG

Other Intervention Names

LDV\SOF

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cairo University

OTHER

Sponsor Role: collaborator

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Manal Hamdy El-Sayed

Professor of Pediatrics and Director of the Clinical Research Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Manal H Elsayed, MD

Role: PRINCIPAL_INVESTIGATOR

Ain Shams University

Locations

Faculty of Medicine Ain Shams Research Institute- Clinical Research Center (MASRI-CRC)

Cairo, Cairo Governorate, Egypt

Pediatric Hematology Oncology and BMT Department, Faculty of Medicine, Ain Shams University

Cairo, , Egypt

Countries

Egypt

References

AbdelMagid AM, Abbassi MM, Ebeid FS, El-Sayed MH, Farid SF. Population Pharmacokinetics of Ledipasvir/Sofosbuvir in Pediatric Patients: Impact of Acute Lymphoblastic Leukemia. Clin Ther. 2025 Feb;47(2):e5-e15. doi: 10.1016/j.clinthera.2024.11.022. Epub 2024 Dec 19.

Reference Type: DERIVED

PMID: 39706761 (View on PubMed)

AbdelMagid AM, Abbassi MM, Ebeid FS, Farid SF, El-Sayed MH. Ledipasvir/Sofosbuvir in Hepatitis C Virus-Infected Children With Hematological Malignancies: A Pharmacokinetic Study. Clin Ther. 2024 Jan;46(1):e12-e22. doi: 10.1016/j.clinthera.2023.10.007. Epub 2023 Nov 3.

Reference Type: DERIVED

PMID: 37925363 (View on PubMed)

Other Identifiers

CL 3062

Identifier Type: -

Identifier Source: org_study_id