A Phase II Dose-escalation Study Characterizing the PK of Eltrombopag in Pediatric Patients With Previously Untreated or Relapsed Severe Aplastic Anemia or Recurrent Aplastic Anemia

Prior and/or active medical history of:

* Fanconi anemia (via chromosome breakage test or growth arrest by flow cytometry)

* Other known underlying inherited marrow failure syndrome (such as but not limited to Dyskeratosis Congenita, Congenital Amegakaryocytic Thrombocytopenia, or Shwachman-Diamond Syndrome).

Symptomatic Paroxysmal Nocturnal Hemoglobinuria (PNH) and/or PNH clones \>50% of White blood cell (WBC) or Red blood cell (RBC) at time of enrollment.

* Any cytogenetic abnormalities by karyotyping or FISH.

* Myelodysplastic syndrome (MDS)

* Other known or suspected underlying primary immunodeficiency

* Any malignancy

Active infection not responding to appropriate therapy.

Prior eltrombopag or other thrombopoietin receptor (TPO-R) agonist treatment for at least 2 months and a lack of response.

Have any of the following out-of-range laboratory values:

* Serum Creatinine \>2.5 × upper limit of normal (ULN),

* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 × ULN.

Concurrent participation in an investigational study within 30 days prior to enrollment or within 5-half-lives of the investigational product, whichever is longer. Note: a parallel enrollment in a registry for patients with SAA or AA is acceptable.

Pregnant or nursing (lactating) women.

Female patients of childbearing potential (e.g., are menstruating or could reach menarche during the study, this usually includes girls 9 years and older) who do not agree to abstinence or, if sexually active, do not agree to the use of contraception as defined in Section 7.2.1.2.6 (pregnancy section) of the protocol. If local regulations are more stringent than the contraception methods listed in this protocol to prevent pregnancy, local regulations apply and will be described in the ICF.

Male patients who are sexually active and do not agree to abstinence or to use a condom during intercourse while taking eltrombopag, and for 13 weeks after stopping treatment.

Patients, who in the investigators' opinion may be unwilling, are unable or unlikely to comply with the requirements of the study protocol.

Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or its excipient, CSA, or hATG that contraindicates patient participation.

History of major surgery, serious illness, or traumatic injury within 4 weeks of first dose of study treatment.

Patients with known history of HIV positivity.

Patients with known history of hepatitis B or C positivity.

Any severe and/or uncontrolled medical conditions which could cause unacceptable safety risks or compromise compliance with the protocol, such as:

• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome),Active skin, mucosa, ocular or GI disorders of Grade \> 1.

Impaired cardiac function, such as:

* Patients with a history of congenital long QT syndrome or known family history of long QTc syndrome,

* Corrected QTc \>450 msec using Fridericia correction (QTcF) on the screening ECG (using triplicate ECGs),

* Ventricular arrhythmias and or other cardiac arrhythmia not controlled with medication,

* Other clinically significant cardio-vascular disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension),

* History of known structural abnormalities (e.g., cardiomyopathy).

What this study is about