Wiskott-Aldrich syndrome (WAS) is a life-threatening primary immunodeficiency associated with bleeding of variable severity due to severe thrombocytopenia. Considering that the hemorrhagic events are a cause of death in 21% of WAS patients, management of thrombocytopenia constitutes a major challenge. Findings of defective platelet production by megakaryocytes and reduced in vitro pro-platelet formation suggested the possibility of megakaryocyte stimulation by TPO-RAs romiplostim, eltrombopag as a treatment strategy. Each of them has distinct pharmacodynamic, pharmacokinetic properties, different effects on megakaryopoiesis, and might have different efficacy in individual patients.~The aim of this study is to compare the efficacy and safety of romiplostim and another TPO-RA eltrombopag for the treatment of thrombocytopenia in patients with WAS and assess the benefit of switching these molecules in refractory subjects. The patients will be randomized in a 1:1 fashion to receive either romiplostim or eltrombopag.~After enrollment, (see detailed inclusion and exclusion criteria below) subjects under 18 years of age with a confirmed diagnosis of WAS and thrombocytopenia (platelet count of less than 70 x 109/L) will be assigned to receive romiplostim at an initial dose of 9 µg/kg subcutaneously per week or oral eltrombopag at a dose of 2-3mg/kg daily (ages 1 to 5 years) and 75 mg/daily (>6 years) for at least 1 month.~Bleeding severity will be evaluated with a modified World Health Organization (WHO) Bleeding Scale, lab tests (blood counts, biochemical analyses), ECG will be assessed after 30 days of treatment (30 +/- 7 days).~The efficacy of romiplostim/eltrombopag will be defined by the following criteria: complete response -an achievement of the platelet count >100 x 109/L, partial - platelet count at least 30 x 109/L higher than the patient's pretreatment baseline count up to to 100 x 109/L. No response will be defined as not achieving a platelet count of > 30 x 109/L from the baseline count.~Refractory patients will be switched to alternate TPO-RA agonist. Other reasons for switching that are not related to efficacy might include adverse events, active colitis, patient preference.
This is a prospective, open-label, randomized, two-arm clinical trial conducted to evaluate the safety and efficacy of romiplostim in comparison with eltrombopag in the treatment of thrombocytopenia in patients with Wiskott-Aldrich syndrome