Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Subjects With Hepatitis C Related Liver Disease
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Intervention: eltrombopag; placebo
Intervention description: 25, 50, 75, 100 mg tablets taken once daily orally; matched placebo taken once daily orally
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 687.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: thrombopoietin; hepatitis C; ribavirin; platelets; Hepatitis C-related thrombocytopenia; peginterferon alfa-2a

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, antithrombin III (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