Early Initiation of Oral Therapy With Cyclosporine and Eltrombopag for Treatment Naive Severe Aplastic Anemia (SAA)

• INCLUSION CRITERIA:

1. Age >= 3 years old

2. Weight >12Kg

3. Severe aplastic anemia:

• Bone marrow cellularity <30% (excluding lymphocytes) AND At least two of thefollowing:

• Absolute neutrophil count <500/microliter

• Platelet count <20,000/microliter

• Absolute reticulocyte count <60,000/microliter

EXCLUSION CRITERIA:

1. Known diagnosis or high suspicion of Fanconi anemia or other constitutional marrowfailure syndrome

2. Evidence of a clonal disorder on cytogenetics performed within 12 weeks of studyentry involving chromosome 7 or complex karyotype. Patient will not be excluded ifcytogenetics are not done or are pending

3. A course of prior immunosuppressive therapy (ATG, cyclosporine, alemtuzumab, andhigh dose cyclophosphamide), or eltrombopag

4. SGOT or SGPT >2.5 times the upper limit of normal or total bilirubin >1.5 x upperlimit of normal

5. Subjects with liver cirrhosis (as determined by the investigator).

6. Subjects with human immunodeficiency virus (HIV) who are not receivingantiretroviral therapy, have detectable HIV RNA viral load and have CD4 cell count <200/microliter, or are on anti-retroviral therapy that interacts with the studydrugs. subjects will not be excluded if HIV testing is pending or unavailable.

7. Glomerular filtration rate (GFR) <40 mL/min/1.73m^2

8. Hypersensitivity to EPAG or its components

9. Infection not adequately responding to appropriate therapy

10. Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary,infectious, or metabolic disease of such severity that it would preclude thepatient's ability to tolerate protocol therapy, or that death within 7-10 days islikely

11. Potential subjects with cancer who are on active chemotherapeutic treatment or whotake drugs with hematological effects will not be eligible

12. Inability to understand the investigational nature of the study or to give informedconsent or does not have a legally authorized representative or surrogate that canprovide informed consent.

13. Inability to swallow

14. Unable to participate in audio/video telecommunication

15. Inability to ship the study drug to participant

16. History or current diagnosis of cardiac disease indicating significant risk ofsafety for patients participating in the study such as uncontrolled or significantcardiac disease, including any of the following: Recent myocardial infarction (within last 6 months), uncontrolled congestive heart failure, unstable angina (within last 6 months), clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or thirddegree AV block without a pacemaker.), long QT syndrome, family history of idiopathic sudden death, congenital long QT syndrome oradditional risk factors for cardiac repolarization abnormality, as determined by theinvestigator.

17. Impaired cardiac function, such as: Corrected QTc >450 msec using Fridericiacorrection (QTcF) on the screening ECG (using triplicate ECGs), other clinicallysignificant cardiovascular disease (e.g., uncontrolled hypertension, history oflabile hypertension), history of known structural abnormalities (e.g.cardiomyopathy).

18. Concurrent participation in an investigational study within 30 days prior toenrollment or within 5-half-lives of the investigational product, whichever islonger. Note: parallel enrollment in a disease registry is permitted.

19. Known thrombophilic risk factors. Exception: Subjects for whom the potentialbenefits of participating in the study outweigh the potential risks ofthromboembolic events, as determined by the investigator.

20. Women of child-bearing potential, defined as all women physiologically capable ofbecoming pregnant, unless they are using basic methods of contraception duringdosing of study treatment. Basic contraception methods include:

• Total abstinence (when this is in line with the preferred and usual lifestyleof the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,post-ovulation methods) and withdrawal are not acceptable methods of contraception

• Female sterilization (have had surgical bilateral oophorectomy with or withouthysterectomy), total hysterectomy, or tubal ligation at least six weeks beforetaking study treatment. In case of oophorectomy alone, only when thereproductive status of the woman has been confirmed by follow up hormone levelassessment

• Male sterilization (at least 6 months prior to screening). The vasectomizedmale partner should be the sole partner for that subject

• Barrier methods of contraception: Condom or Occlusive cap. For the UK: withspermicidal foam/gel/film/cream/ vaginal suppository

• Use of oral, injected or implanted hormonal methods of contraception orplacement of an intrauterine device (IUD) or intrauterine system (IUS), orother forms of hormonal contraception that have comparable efficacy (failurerate <1%), for example hormone vaginal ring or transdermal hormonecontraception.

• In case of use of oral contraception women should have been stable on thesame pill for a minimum of 3 months before taking study treatment.

21. Female subjects who are nursing or pregnant (positive serum or urine B-humanchorionic gonadotrophin (B-hCG) pregnancy test) at screening or pre-dose on Day 1

22. Sexually active males unless they use a condom during intercourse while taking thedrug during treatment, and for 7 days after stopping treatment (and for anadditional 12 weeks [for genotoxic compounds]) and should not father a child in thisperiod. A condom is required to be used also by vasectomized men as well as duringintercourse with a male partner in order to prevent delivery of the drug via semen.