Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Benefit Subjects With Hepatitis C Liver Disease
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Intervention: eltrombopag; placebo
Intervention description: double-blind active treatment daily oral administation at dose of 25, 50, 75, or 100 mg; double-blind matched placebo control daily oral administration
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 759.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hepatitis C; ribavirin; Hepatitis C-related thrombocytopenia; thrombopoietin; peginterferon alfa-2b; platelets

Summary:

      The purpose of this study is to assess the ability of eltrombopag to maintain a platelet
      count sufficient to facilitate initiation of antiviral therapy, to minimise antiviral therapy
      dose reductions and to avoid permanent discontinuation of antiviral therapy. The clinical
      benefit of eltrombopag will be measured by the proportion of subjects who are able to achieve
      a Sustained Virological Response (SVR).
    

Eligibility criteria:

        Inclusion Criteria:

        Male and female subjects, >18 years Evidence of chronic hepatitis C virus (HCV) infection
        Subjects who are appropriate candidates for peginterferon (pegIFN) and ribavirin antiviral
        therapy A platelet count of <75,000/mcL Haemoglobin >11.0g/dL for men or >10.0g/dL for
        women Absolute neutrophil count (ANC) >750/mm3 and no history of infections associated with
        neutropenia Creatinine clearance >50mL/minute All fertile males and females must use two
        forms of effective contraception between them during treatment and during the 24 weeks
        after treatment end Subject is able to understand, consent and comply with protocol
        requirements and instructions and is likely to complete the study as planned

        Exclusion criteria:

        Non-responders to previous treatment with pegIFN and ribavirin who failed to achieve a
        sustained virologic response (SVR) for reasons other than thrombocytopenia, despite an
        optimal course (dose and duration) of combination therapy with pegIFN and ribavirin
        Decompensated liver disease, e.g. Child-Pugh score >6 or history of ascites or hepatic
        encephalopathy or current evidence of ascites Known hypersensitivity, intolerance or
        allergy to interferon (IFN), ribavirin, eltrombopag or any of their ingredients Serious
        cardiac, cerebrovascular, or pulmonary disease that would preclude treatment with pegIFN
        and ribavirin

        Subjects with a history of any one of the following:

        Suicide attempt or hospitalisation for depression in the past 5 years Any current severe or
        poorly controlled psychiatric disorder

        The following subjects are eligible for study participation, but must be assessed and
        followed (if recommended) by a mental health professional:

          -  Subjects who have had a severe or poorly controlled psychiatric disorder more than 6
             months ago but less than 5 years ago

          -  Seizure disorder that has not been well controlled History of clinically significant
             bleeding from oesophageal or gastric varices Subjects with haemoglobinopathies, e.g.
             sickle cell anaemia, thalassemia major Any prior history of arterial or venous
             thrombosis AND two or more of the following risk factors: hereditary thrombophilic
             disorders (e.g. Factor V Leiden, ATIII deficiency, etc), hormone replacement therapy,
             systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia,
             medication for hypertension or cancer Pre-existing cardiac disease (New York Heart
             Association (NYHA) Grade III/IV), or arrhythmias known to involve the risk of
             thromboembolic events, or corrected QT interval (QTc) >450 msec Evidence of
             hepatocellular carcinoma Laboratory evidence of infection with human immunodeficiency
             virus (HIV) or active Hepatitis B Virus (HBV) infection Any disease condition
             associated with active bleeding or requiring anticoagulation with heparin or warfarin
             Therapy with any anti-neoplastic or immuno-modulatory treatment <6 months prior to the
             first dose of eltrombopag.

        Subjects who have had a malignancy diagnosed and/or treated within the past 5 years, except
        for subjects with localised basal or squamous cell carcinoma treated by local excision or
        subjects with malignancies who have been adequately treated and, in the opinion of the
        oncologist, have an excellent chance of cancer-free survival Pregnant or nursing women
        Males with a female partner who is pregnant History of alcohol/drug abuse or dependence
        within 6 months of the study start (unless participating in a controlled rehabilitation
        programme) Treatment with an investigational drug or IFN within 30 days or 5 half-lives
        (whichever is longer) of the screening visit History of platelet clumping that prevents
        reliable measurement of platelet counts History of major organ transplantation with an
        existing functional graft Thyroid dysfunction not adequately controlled Subjects planning
        to have cataract surgery Evidence of portal vein thrombosis on abdominal imaging within 3
        months of the baseline visit