Sofosbuvir/Ledipasvir for Hepatitis C Genotype 1-6 in Patients With Transfusion-Dependent Thalassemia: An Open Label Trial

October 10, 2018 updated by: Ala'a Sharara

Sustained Viral Response following 12-week therapy (SVR 12) with sofosbuvir/ledipasvir in transfusion-dependent patients with HCV genotype 1-6

Secondary Objective(s):

Assessment of transfusion requirements Adverse events Efficacy in treatment-naïve vs. relapsers vs. null responders Efficacy in patients with advanced fibrosis/cirrhosis vs. F1, F2 by elastography

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Thalassemia is characterized by a defect in red blood cell production. The anemia is caused by destruction of the erythroblasts in the bone marrow, erythrocytes' hemolysis and disrupted erythropoiesis. The life-long need for transfusions makes patients vulnerable to transfusion transmitted viral infections especially hepatitis C virus (HCV). HCV infection is a widespread disease. It affects a large number of thalassemia patients and it is considered a major public health problem. Infection with HCV results in chronic infection in a huge proportion of infected individuals. Therefore, it has been suggested that early treatment of acute HCV may prevent the development of chronic hepatitis.

Several studies have dwelled on the efficacy of interferon therapy for acute HCV infection in adults. Newer pegylated interferons (PEG-IFN) were used in the treatment of adults with acute HCV which showed equally excellent results. However, in thalassemia patients, iron overload in the liver negatively affects the outcome of liver disease leading to more severe hepatic inflammation and fibrosis in chronic hepatitis C which decreases response to IFN therapy.

Ribavarin has also been added as a treatment option with IFN, but ribavirin in thalassemia patients increases transfusion need by a median of 30-40 %, but does not increase major adverse events or treatment withdrawal.

At the end of 2013, the Food and Drug Administration (FDA) approved a new direct-acting antiviral agent for the treatment of HCV infection: Sofosbuvir (Gilead Sciences). Ledipasvir (Gilead Sciences) is a new drug with potent activity against HCV genotypes 1a and 1b. The combination of ledipasvir and sofosbuvir resulted in high rates of response among patients with HCV genotype 1 infection who had received prior treatment with interferon-based regimens. Ledipasvir and sofosbuvir have been combined in a single fixed-dose tablet for use once daily (ledipasvir-sofosbuvir).

Using this drug for HCV therapy alone or in combination with IFN for 12 or 24 weeks, resulted in more than 90% response rates in patients from the general population.

Patients with transfusion-dependent thalassemia major are at increased risk of adverse events with pegylated interferon and ribavirin therapy for HCV due to a notable 30% increase in transfusion requirements during the 48-week therapy. Some patients are not eligible for other treatments as they relapsed or did not respond to previous Ribavarin and IFN regimens. Treatment naïve thalassemia patients with HCV will be exposed to anemia and transfusion-induced iron overload among other adverse events associated with Ribavarin and IFN. These patients in particular, in addition to treatment-naïve thalassemia patients, have limited alternative treatment options available and constitute an area of significant unmet clinical needs. There is currently no literature available showing the efficacy of sofosbuvir/ledipasvir in the treatment of thalassemia patients with hepatitis C. Therefore, this trial will study the efficacy of sofosbuvir/ledipasvir for hepatitis C genotype 1-6 in patients with transfusion-dependent thalassemia.

Ten patients from the Lebanese Chronic Care Center will be enrolled in this open label trial. Patients with transfusion dependent thalassemia with hepatitis C will be enrolled. Study patients will receive the treatment following informed consent and will be followed up regularly by the study coordinator for side effects, compliance and adherence. A blood test for hemoglobin and hematocrit and liver enzyme, will be done on all patients at baseline and then after 4 weeks, 8 weeks , and 12 weeks of therapy. At week 12, levels of the virus in the patient's blood will also be evaluated. Liver imaging will be done throughout the study.

Benefits of this study outweigh potential risks. Side effects of medications used are minor however potential benefits for the patients are possibly treating their hepatitis C with an approved drug (in the general population) at no cost, and for the society, the possibility of finding an oral treatment more efficient and tolerable in this special population.

As for privacy and confidentiality issues, all data will be under lock. The PI and the Co- Investigators will be the only ones with access to that data.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Lebanon
      • Beirut, Lebanon
        • American University of Beirut Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Transfusion Dependent thalassemia patients with HCV genotype 1-6
  • Age ≥18
  • Male and female
  • No evidence of hepatocellular carcinoma on ultrasound
  • No known drug allergy to the FDA approved drug to be used
  • Adequate iron chelation therapy
  • Compensated liver disease

Exclusion Criteria:

  • Age below 18
  • Chronic HCV genotypes 2 or 3
  • Allergy to study drug
  • Hepatocellular carcinoma
  • Inadequate iron chelation therapy
  • Decompensated liver disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: sofosbuvir/velpatasvir
Epclusa
Drug: sofosbuvir/velpatasvir
treatment of hepatitis C genotype 1-6 in patients with transfusion-dependent thalassemia.
Other Names:
  • Epclusa

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sustained Viral Response following 12-week therapy (SVR 12) with sofosbuvir/velpatasvir in transfusion-dependent patients with HCV genotype 1-6
Time Frame: 12 weeks
Via tests of HepC RNA levels
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ala'a Sharara

Collaborators

Gilead Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2017

Primary Completion (Actual)

August 6, 2018

Study Completion (Actual)

August 6, 2018

Study Registration Dates

First Submitted

January 24, 2017

First Submitted That Met QC Criteria

January 25, 2017

First Posted (Estimate)

January 26, 2017

Study Record Updates

Last Update Posted (Actual)

October 11, 2018

Last Update Submitted That Met QC Criteria

October 10, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IM.AS1.47

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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