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

For Cohort A:

1. Prior history of diagnosis of SAA

2. Diagnosis of relapsed/refractory SAA or recurrent AA following IST for SAA at the time
of enrollment. Patients with recurrent AA (e.g., losing their response) are exempt
from meeting the diagnostic criteria for relapsed SAA at the time of enrollment, but
must have been previously diagnosed with SAA.

3. Agree to concurrent eltrombopag treatment with appropriate, investigator-selected IST
with either hATG + CsA or CsA.

For Cohort B:

4. Diagnosis of SAA at the time of enrollment

5. Patients must not have been previously treated for SAA

6. Patients must agree to treatment with hATG + CsA concurrent with eltrombopag.

For all patients, regardless of cohort:

7. Age 1 to <18 years

8. Where appropriate, assessments to rule out congenital/inherited bone marrow failure
syndromes and other causes of immune-mediated pancytopenia, which may be treated with
transplant, must be completed prior to enrollment.

9. Hematopoietic stem cell transplantation (HSCT) is not available or suitable as a
treatment option or has been refused by the patient. (Candidacy for HSCT will be
determined as per local practice.)

10. Bone marrow aspirate and biopsy at any time during the 4 weeks prior to first dose of
eltrombopag

11. Normal karyotype with FISH for chromosomes 7 and 8

12. Performance status score: Karnofsky ≥50 or Lansky ≥50 (depending on age)

13. Serum creatinine ≤2.5 × ULN

14. Total bilirubin ≤1.5 × ULN

15. Written informed consent signed by a parent or legal guardian prior to initiation of
any study specific procedure.

Exclusion Criteria:

1. Prior and/or active medical history of:

- Fanconi anemia (via chromosomal breakage test or growth arrest by flow cytometry)

- Other known underlying congenital/inherited marrow failure syndromes

- Symptomatic Paroxysmal Nocturnal Hemoglobinuria (PNH) and/or PNH clones >50% of
PMN or RBC at time of enrollment

- Any cytogenetic abnormalities, including but not limited to chromosome 7 or
myelodysplasia, in bone marrow within 4 weeks of study enrollment

- Myelodysplastic syndrome (MDS)

- Other known or suspected underlying primary immunodeficiency

- Any malignancy

2. Active infection not responding to appropriate therapy

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

4. Any out of range lab values Creatinine >2.5 × upper limit of normal (ULN), Total
bilirubin >1.5 × ULN Aspartate aminotransferase (AST) or alanine aminotransferase
(ALT) >2.5 × ULN