Eltrombopag for Inherited Thrombocytopenias
Condition: Inherited Platelet Disorder
MeSH terms: Thrombocytopenia; Blood Platelet Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      Inherited thrombocytopenias (ITs) are a heterogeneous group of disorders characterized by a
      reduced number of blood platelets and a consequent bleeding tendency that ranges from mild to
      life-threatening. Thrombocytopenia is caused by genetic mutations and therefore is present
      throughout life and can be transmitted to the progeny. Some patients with severely reduced
      platelet count present spontaneous bleeding, which represents a major clinical problem: in
      fact, bleeding diathesis exposes these subjects to the risk of severe hemorrhages, affects
      their quality of life and often requires hospitalization and/or transfusions. Conversely,
      other patients with ITs have absent or mild spontaneous bleeding tendency. However, even
      these patients are at risk of major bleeding on the occasion of surgery or other invasive
      procedures. Therefore, the potential for hemorrhages on the occasion of invasive procedures
      represent a clinical problem for all patients affected by ITs.

      Eltrombopag is a drug, available in tablets, which stimulates the production of platelets by
      the bone marrow. A previous study demonstrated that a short course of eltrombopag was
      effective in increasing platelet count in most patients with the MYH9-related disease
      (MYH9-RD), the most frequent form of IT. Eltrombopag was given for 3 to 6 weeks to 12
      patients with MYH9-RD and platelet counts lower than 50 x10e9/L. Eleven patients responded to
      the drug and 8 of them obtained platelet counts higher than 100 x10e9/L or three times the
      baseline value. Remission of spontaneous bleeding was achieved by 8 of 10 patients and
      treatment was well tolerated in all the cases. Based on these findings, short-term
      eltrombopag courses have been successfully used for preparing for major surgery two patients
      with MYH9-RD and less than 20 x10e9 platelets/L.

      The present study has two main objectives. - To verify if eltrombopag is effective in
      transiently increasing platelet count over 100 x 10e9/L and abolishing bleeding tendency in
      patients with different forms of IT.

      To this end, eltrombopag will be given for 3-6 weeks to patients with different forms of IT.
      Eltrombopag will be administered at the dose of 50 mg/day for 3 weeks. After 3 weeks of
      treatment, the patients who will obtain a platelet count higher than 100 x10e9/L and complete
      remission of bleeding tendency will stop therapy. In the other cases, patients will be
      treated with eltrombopag at a higher dose (75 mg/day) for 3 additional weeks. This treatment
      schedule is called "Phase 1" of the study.

      If the study will achieve this goal, short-term eltrombopag could be potentially used in the
      future to prepare these patients for surgery or other invasive procedures

      - To verify if eltrombopag can be used to stably reduce spontaneous bleeding tendency for
      long periods of time in patients with clinically significant spontaneous hemorrhages.

      To this end, patients with clinically significant spontaneous bleedings at baseline and who
      had their bleeding tendency reduced during the Phase 1 of the study without severe side
      effects, will be admitted to the "Phase 2" of the study.

      During the Phase 2, patients will be treated with eltrombopag for 16 weeks. In order to
      determine the lowest dose of eltrombopag that is able to reduce or abolish their bleeding
      tendency, patients will start treatment with eltrombopag 25 mg/day for 4 weeks. Then, every 4
      weeks, patients will be re-evaluated and the dosage of eltrombopag will be adjusted according
      to bleeding tendency and platelet count. The dosages of eltrombopag that can be used in the
      Phase 2 range from 12.5 to 75 mg/day.

      Other objectives of the study are:

        -  to evaluate safety and tolerability of Eltrombopag in patients affected with ITs.

        -  to identify the dosages of Eltrombopag required for achieving the primary endpoints of
           Phases 1 and 2.

        -  to study the effects of Phase 2 treatment on patients' health-related quality of life
           (HR-QoL);

        -  to study the effects of treatment on some laboratory parameters related to platelet
           production and function.

      All patients will be undergo a follow-up visit 30 days after completion of treatment.

      Patients will be treated as outpatients. The evaluation of patients at enrollment and at each
      subsequent on-treatment and post-treatment visits includes: medical history; physical
      examination; evaluation of bleeding tendency according to WHO bleeding scale; CBC and
      differential; platelet count by phase-contrast microscopy; peripheral blood smear
      examination; plasma transaminases, bilirubin, and creatinine; urine analysis; ophthalmic
      assessment (only at some visits); measurement of serum thrombopoietin level; evaluation of
      HR-QoL (only at baseline and during Phase 2); evaluation of in vitro platelet aggregation in
      response to ADP, collagen and ristocetin whenever platelet count is over 100 x 10e9/L.
    


Intervention name(s): Eltrombopag
Intervention type(s): Drug
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment