Sofosbuvir/Ledipasvir for Hepatitis C Genotype 1-6 in Patients With Transfusion-Dependent Thalassemia: An Open Label Trial
Condition: Thalassemia; Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Thalassemia
Study type: Interventional
Phase: Phase 4

Summary: 
      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
    

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.
    

Intervention name(s): sofosbuvir/velpatasvir
Intervention type(s): Drug
Intervention description(s): treatment of hepatitis C genotype 1-6 in patients with transfusion-dependent thalassemia.
Other intervention name(s): Epclusa
Intervention MeSH terms: Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Velpatasvir
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Thalassemia; HCV; Sofosbuvir; Ledipasvir