Refractory, relapsed or treatment naïve severe aplastic anemia (SAA) or recurrent aplastic anemia (AA) MedDRA version: 20.0 Level: PT Classification code 10002967 Term: Aplastic anaemia System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria specific to Cohort A (patients with relapsed/refractory SAA or recurrent AA): 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. Inclusion Criteria specific to Cohort B (patients with previously untreated SAA): 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. Inclusion Criteria for all patients regardless of cohort: 7. Age 1 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 2. 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 (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 PMN or RBC at time of enrollment • Any cytogenetic abnormalities by karyotyping or FISH • Myelodysplastic syndrome (MDS) • Other known or suspected underlying primary immunodeficiency • Any malignancy 3. Active infection not responding to appropriate therapy 4. Prior eltrombopag or other thrombopoietin receptor (TPO-R) agonist treatment for at least 2 months and a lack of response. 5. Any out of range lab values: • Serum Creatinine >2.5 × upper limit of normal (ULN), • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × ULN.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Key secondary objectives: 1. To determine the safety and tolerability of eltrombopag given orally in pediatric patients with SAA. 2. To assess the efficacy defined as overall response (ORR). Other secondary endpoints: 3. To assess hematologic counts. 4. To evaluate PLT and RBC transfusion independence. 5. To assess bone marrow cellularity, morphology (trephine biopsy) and cytogenetics. 6. To assess the acceptability and palatability for the PfOS. 7. To assess clonal evolution to PNH. 8. To characterize the exposure-response relationship of eltrombopag and overall response and PLT response. 9. To assess the efficacy defined as the alternate overall response (aORR). 10. To characterize the PK of eltrombopag at the starting dose;Main Objective: To characterize the PK of eltrombopag at the highest dose after oral administration in pediatric patients with SAA.;Primary end point(s): Cohort A and Cohort B: eltrombopag PK parameters, including AUCtau, Cmax and Ctrough at the highest dose level ;Timepoint(s) of evaluation of this end point: 11 weeks (Week 12 Day 1) after initiation of eltrombopag treatment, or later, as applicable. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a) To determine the safety and tolerability of eltrombopag given orally in pediatric patients with SAA. b) To assess the efficacy of eltrombopag defined as overall response rate (ORR) ;Timepoint(s) of evaluation of this end point: a) Assessed throughout the study. b) At Week 12, Week 26, Week 52, and Week 78. | — |
Countries
Hong Kong, Netherlands, Portugal, Russian Federation, Thailand, United Kingdom, United States
Contacts
Public ContactMedica Information Services
Novartis Pharmaceuticals UK Limited
Outcome results
None listed