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

Primary Purpose

HCV Infection, Beta Thalassemia Major

Status

Recruiting

Phase

Phase 3

Locations

Egypt

Study Type

Interventional

Intervention

Sofosbuvir and Ledipasvir

About this trial

This is an interventional treatment trial for HCV Infection focused on measuring Hepatitis C virus, Pharmacokinetic Modeling, Pharmacokinetics, Sofosbuvir, Ledipasvir, Direct acting antivirals, Beta thalassemia major

Eligibility Criteria

12 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Masri-CrcRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Beta thalassemia

Control

Arm Description

HCV infected Beta thalassemia major adolescents

HCV infected, otherwise healthy, sex and age matched to the thalassemia group serving as control group

Outcomes

Primary Outcome Measures

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

sustained virologic response

Secondary Outcome Measures

adverse drug reactions

record any adverse drug reactions experienced by the patients

Full Information

NCT ID

NCT04353986

First Posted

July 15, 2019

Last Updated

March 3, 2023

Sponsor

Ain Shams University

1. Study Identification

Unique Protocol Identification Number

NCT04353986

Brief Title

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

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 11, 2018 (Actual)

Primary Completion Date

April 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Ain Shams University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HCV Infection, Beta Thalassemia Major

Keywords

Hepatitis C virus, Pharmacokinetic Modeling, Pharmacokinetics, Sofosbuvir, Ledipasvir, Direct acting antivirals, Beta thalassemia major

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

This is a prospective, interventional, controlled, open-label, pharmacokinetic study.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Beta thalassemia

Arm Type

Experimental

Arm Description

HCV infected Beta thalassemia major adolescents

Arm Title

Control

Arm Type

Active Comparator

Arm Description

HCV infected, otherwise healthy, sex and age matched to the thalassemia group serving as control group

Intervention Type

Drug

Intervention Name(s)

Sofosbuvir and Ledipasvir

Other Intervention Name(s)

SOF/LED

Intervention Description

fixed dose tablet containing 400 mg sofosbuvir and 90 mg ledipasvir

Primary Outcome Measure Information:

Title

Predictive Pharmacokinetic Model

Description

serial blood samples will be withdrawn to measure the drug level develop a Predictive Pharmacokinetic Model for sofosbuvir, ledipasvir and GS 331007

Time Frame

10 days

Title

sustained virologic response

Description

sustained virologic response

Time Frame

6 months

Secondary Outcome Measure Information:

Title

adverse drug reactions

Description

record any adverse drug reactions experienced by the patients

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Manal H El-Sayed, M.D.

Phone

01227461120

Ext

002

manalhelsayed@yahoo.co.uk

First Name & Middle Initial & Last Name or Official Title & Degree

Fatma S Ebeid, M.D.

Phone

01095569596

Ext

002

dr.fatma_ebeid@yahoo.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Manal H El-Sayed, M.D

Organizational Affiliation

Director of MARSI-CRC

Official's Role

Principal Investigator

Facility Information:

Facility Name

Masri-Crc

City

Cairo

Country

Egypt

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Manal H El-Sayed, M.D.

Phone

01227461120

Ext

002

manalhelsayed@yahoo.co.uk

First Name & Middle Initial & Last Name & Degree

Fatma S Ebeid, M.D.

Phone

01095569596

Ext

002

dr.fatma_ebeid@yahoo.com

First Name & Middle Initial & Last Name & Degree

Eman A El-Baraky, Ms.C.

First Name & Middle Initial & Last Name & Degree

Nirmeen A Sabry, Ph.D.

First Name & Middle Initial & Last Name & Degree

Maggie M Abbassi, Ph.D

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34186262

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.

Results Reference

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

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