Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body.
Condition: Idiopathic Thrombocytopenic Purpura
MeSH terms: Thrombocytopenia; Purpura; Purpura, Thrombocytopenic, Idiopathic; Purpura, Thrombocytopenic
Intervention: Eltrombopag; Placebo
Intervention description: Thrombopoietin receptor agonist; Placebo with no active pharmaceutical ingredient
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 92.0
Sex: All
Minimum age: 1 Year
Maximum age: 17 Years
Healthy volunteers: No
Keywords: immune thrombocytopenic purpura; pediatrics; chronic ITP; idiopathic thrombocytopenic purpura; eltrombopag; Chronic Immune Thrombocytopenia; platelet disorder; thrombocytopenia

Summary:

      The purpose of this study is to investigate the efficacy, safety and tolerability of
      eltrombopag in children with previously treated chronic immune thrombocytopenia who are
      between 1 and 17 years of age. This is a 2 part study. In part 1, patients will be randomized
      to receive either eltrombopag or placebo for 13 weeks. All patients who complete part 1 will
      enter part 2. In part 2, all patients will receive 24 weeks of eltrombopag.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent must be obtained from the patient's guardian and accompanying
             informed assent from the patient (for children over 6 years old)

          -  Patients must be between 1 year and <18 years of age at Day 1

          -  Patients will have a confirmed diagnosis of chronic ITP for at least 1 year, at
             screening, according to the guidelines published in the International Working Group
             Report

          -  A peripheral blood smear or bone marrow examination will support the diagnosis of ITP
             with no evidence of other causes of thrombocytopenia.

          -  Patients must be refractory or have relapsed after at least one prior ITP therapy, or
             patients must be unable, for a medical reason, to continue other ITP treatments.

          -  Patients must have a Day 1 (or within 48 hours prior) platelet count <30 Gi/L.

          -  Previous therapy for ITP with immunoglobulins (IVIg and anti-D) must have been
             completed at least 2 weeks prior to Day 1, or these therapies must have been completed
             at least 1 week prior to Day 1 and have been clearly ineffective.

          -  Previous treatment for ITP with splenectomy, rituximab and cyclophosphamide must have
             been completed at least 4 weeks prior to Day 1.

          -  Patients treated with concomitant ITP medication (e.g. corticosteroids or
             azathioprine) must be receiving a dose that has been stable for at least 4 weeks prior
             to Day 1.

          -  Patients must have a complete blood count (CBC) not suggestive of another
             hematological disorder.

          -  Patients must have the following laboratory results:

          -  prothrombin time international normalized ratio (INR) and activated partial
             thromboplastin time (aPTT) within 80 to 120% of the normal range.

          -  clinical chemistries that do NOT exceed the upper limit of normal reference range by
             more than 20% for the following: creatinine, ALT, AST, total bilirubin, and alkaline
             phosphatase.

          -  total albumin that is not below the lower limit of normal by more than 10%.

          -  Female patients of child-bearing potential (after menarche) must:

          -  have a negative pregnancy test within 24 hours of first dose of study treatment,

          -  agree and be able to provide a blood or urine specimen for pregnancy testing during
             the study,

          -  agree to use effective contraception during the study and for 28 days following the
             last dose of study treatment, and not be lactating.

          -  Male patients with a female partner of childbearing potential must agree to use
             effective contraception from 2 weeks prior to administration of the first dose of
             study treatment until 3 months after the last dose of study treatment.

          -  In France, a patient will be eligible for inclusion in this study only if either
             affiliated to or a beneficiary of a social security category.

        Exclusion Criteria:

          -  Patients with any clinically relevant abnormality, other than ITP, identified on the
             screening examination or any other medical condition or circumstance, which in the
             opinion of the investigator makes the patient unsuitable for participation in the
             study or suggests another primary diagnosis (e.g. Thrombocytopenia is secondary to
             another disease).

          -  Patients with concurrent or past malignant disease, including myeloproliferative
             disorder.

          -  Patients expected not to be suitable for continuation of their current therapy for at
             least 13 additional weeks.

          -  Patients with a history of platelet agglutination abnormality that prevents reliable
             measurement of platelet counts.

          -  Patients with a diagnosis of secondary immune thrombocytopenia, including those with
             laboratory or clinical evidence of HIV infection, anti-phospholipid antibody syndrome,
             chronic hepatitis B infection, hepatitis c virus infection, or any evidence of active
             hepatitis at the time of subject screening.

          -  Patients with Evans syndrome (autoimmune thrombocytopenia and autoimmune hemolysis).

          -  Patients with known inherited thrombocytopenia (e.g. MYH9 disorders).

          -  Patients treated with any medication that affects platelet function (including but not
             limited to aspirin, clopidogrel and/or NSAIDS) or anti-coagulants for >3 consecutive
             days within 2 weeks of Day 1.

          -  Patients who have received treatment with an investigational drug within 30 days or 5
             half-lives (whichever is longer) preceding Day 1.

          -  Patients who have previously received eltrombopag or any other thrombopoietin receptor
             agonist.

          -  Any patient considered to be a child in care, defined as one who has been placed under
             the control or protection of an agency, organization, institution or entity by the
             courts, the government or a government body, acting in accordance with powers
             conferred on them by law or regulation. This can include a child cared for by foster
             parents or living in a care home or institution, provided that the arrangement falls
             within the definition above. The definition of a child in care does not include a
             child who is adopted or who has an appointed legal guardian.

          -  Patients who have a known immediate or delayed hypersensitivity reaction or
             idiosyncrasy to drugs chemically related to eltrombopag or excipients that
             contraindicates their participation.

          -  Any serious and/or unstable pre-existing medical, psychiatric disorder, or other
             conditions that could interfere with the patient's safety or compliance to the study
             procedures.