Clinical trial NCT03903185: Pharmacokinetics of Ledipasvir/Sofosbuvir in Hepatitis C Virus-Infected Children With Hematological Malignancy
Official title: Pharmacokinetics of Ledipasvir/Sofosbuvir in Hepatitis C Virus-Infected Children With Hematological Malignancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hepatitis C, Chronic
Hematologic Malignancy
Keywords: Hepatitis C virus
Pharmacokinetic Modeling
Pharmacokinetics
Pediatrics
Leukemia
Ledipasvir
Sofosbuvir
Antiviral Drugs
Lead sponsor: Ain Shams University
Sponsor class: OTHER
Collaborators: name: Cairo University
First posted: 2019-04-04
Enrollment: 24
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Measurement of the pharmacokinetics of LDV\SOF
timeFrame: Blood samples will be collected after 10 days of treatment
Secondary outcomes:
measure: Measurement of the number of participants with sustained virological response (SVR12), 12 weeks after discontinuation of therapy with ledipasvir-sofosbuvir (LDV-SOF).
timeFrame: 12 weeks after discontinuation of therapy with ledipasvir-sofosbuvir (LDV\SOF)
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Faculty of Medicine Ain Shams Research Institute- Clinical Research Center (MASRI-CRC)
state: Al Qāhirah
city: Cairo
country: Egypt
facility: Pediatric Hematology Oncology and BMT Department, Faculty of Medicine, Ain Shams University
Study officials:
affiliation: Ain Shams University
name: Manal H Elsayed, MD
role: PRINCIPAL_INVESTIGATOR
References: