A Longitudinal 2-year Bone Marrow Study of Eltrombopag in Previously Treated Adults, With Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
Condition: Purpura, Thrombocytopaenic, Idiopathic
MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic
Intervention: Eltrombopag olamine
Intervention description: Thrombopoietin receptor agonist
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 167.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immune (idiopathic) thrombocytopenic purpura (ITP); bone marrow fibers; eltrombopag olamine; thrombopoietin receptor agonist

Summary:

      A open-label, multi-center 2-year safety study to ascertain the baseline levels of bone
      marrow fibers in previously treated adults with chronic immune (idiopathic) thrombocytopenic
      purpura (ITP) and to evaluate the long-term effect of eltrombopag on bone marrow fibers. The
      study will also describe the long-term safety and tolerability of oral eltrombopag treatment
      in subjects with chronic ITP.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must have signed and dated a written informed consent and be able to
             understand and comply with protocol requirements and instructions.

          -  Adults (≥18 years) diagnosed with chronic ITP according to the American Society for
             Hematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines
             [George, 1996; BCSH, 2003; Provan, 2009]. In addition, a peripheral blood smear should
             support the diagnosis of ITP with no evidence of other disease causative of
             thrombocytopenia (e.g., pseudo thrombocytopenia, myelofibrosis). The physical
             examination should not suggest any disease, which may cause thrombocytopenia other
             than ITP.

          -  Subjects must be physically eligible for serial bone marrow biopsies and must have a
             bone marrow biopsy performed during screening, and be willing to remain on the study
             for at least 2 years with annual bone marrow biopsies.

          -  Subjects, who previously received eltrombopag or romiplostim, must have completed
             treatment with these therapies at least 6 months prior to the screening bone marrow
             biopsy.

          -  Subjects must have the following clinical chemistry values:

          -  ALT and AST < 2xULN;

          -  Bilirubin <1.5xULN (except for Gilbert's Syndrome);

          -  Subjects are practicing an acceptable method of contraception as specified in the
             protocol.

          -  In France, subjects will be eligible for inclusion in this study, only if either
             affiliated to or a beneficiary of a social security category.

        Exclusion Criteria:

          -  Subjects with any clinically relevant abnormality, other than ITP, or any other
             medical condition or circumstance, which in the opinion of the investigator makes the
             subject unsuitable for participation in the study or suggests another primary
             diagnosis (e.g., thrombocytopenia is secondary to another disease).

          -  Subjects with any concurrent malignant disease and/or a recent history of cancer
             treatment with systemic chemotherapy and/or radiotherapy.

        Exception: Subjects with a history of completely resected non-melanoma skin cancer or
        successfully treated in situ carcinoma are eligible.

          -  Subjects with any prior history of arterial or venous thrombosis (stroke, transient
             ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism),
             AND ≥ two of the following risk factors: hormone replacement therapy, systemic
             contraception (containing estrogen), smoking, diabetes, hypercholesterolemia,
             hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, ATIII
             deficiency, etc), or any family history of arterial or venous thrombosis.

          -  Subjects with screening bone marrow fibers of either MF Grade 3 using European
             Consensus scale or Grade 4 using Bauermeister scale.

          -  Subjects with a QTc >450 msec or > 480 msec for subjects with Bundle Branch Block.

          -  Female subjects who are nursing or pregnant (positive serum or urine β-human chorionic
             gonadotrophin (β-hCG) pregnancy test) at screening.

          -  Subjects treated with an investigational drug (other than a thrombopopoetin-receptor
             (TPO-R) agonist) within 30 days or five half-lives (whichever is longer) preceding the
             first dose of eltrombopag in the study. (For romiplostim or eltrombopag, see inclusion
             criterion #4).

          -  Subjects treated with any TPO-R agonist other than romiplostim or eltrombopag.

          -  Subjects with recent history of alcohol/drug abuse as determined by the investigator.