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.
