Clinical trial NCT04353986: PK of SOF/LED in HCV - Infected Adolescents With Haematological Disorders
Official title: Pharmacokinetics of Sofosbuvir and Ledipasvir in Hepatitis C Virus - Infected Adolescent Patients With Haematological Disorders
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: HCV Infection
Beta Thalassemia Major
Keywords: Hepatitis C virus
Pharmacokinetic Modeling
Pharmacokinetics
Sofosbuvir
Ledipasvir
Direct acting antivirals
Beta thalassemia major
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2020-04-21
Enrollment: 24
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, interventional, controlled, open-label, pharmacokinetic study.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Predictive Pharmacokinetic Model
timeFrame: 10 days
measure: sustained virologic response
timeFrame: 6 months
Secondary outcomes:
measure: adverse drug reactions
timeFrame: 3 months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Masri-Crc
Study officials:
affiliation: Director of MARSI-CRC
name: Manal H El-Sayed, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.