<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03025698</url>
  </required_header>
  <id_info>
    <org_study_id>CETB115E2201</org_study_id>
    <nct_id>NCT03025698</nct_id>
  </id_info>
  <brief_title>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</brief_title>
  <official_title>A Phase II, Open-label, Non-controlled, Intra-patient Dose-escalation Study to Characterize the Pharmacokinetics After Oral Administration of Eltrombopag in Pediatric Patients With Refractory, Relapsed or Treatment Naive Severe Aplastic Anemia or Recurrent Aplastic Anemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase II, open label, multi-center, intra-patient dose escalation study to&#xD;
      characterize the pharmacokinetics (PK) after oral administration of eltrombopag in&#xD;
      combination with immunosuppressive therapy in pediatric patients with previously untreated or&#xD;
      relapsed/refractory severe aplastic anemia or recurrent aplastic anemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All patients will be treated with eltrombopag for the 26-week Treatment Period, followed by a&#xD;
      52-week Follow-Up Period. Patients who have been previously untreated with immunosuppressive&#xD;
      therapy will be treated according to the standard of care, hATG/cyclosporine, in addition to&#xD;
      eltrombopag. Patients with relapsed/refractory SAA or recurrent AA will be enrolled into one&#xD;
      of two treatment options: hATG/cyclosporine plus eltrombopag or cyclosporine plus&#xD;
      eltrombopag, depending on prior treatment with immunosuppressive therapy.&#xD;
&#xD;
      After initiating treatment with eltrombopag, patients will have their dose assessed and&#xD;
      modified as tolerated, until the targeted platelet count or maximum dose is achieved.&#xD;
      Pharmacokinetic assessments will be performed at time points intended to capture steady state&#xD;
      PK of the starting dose and highest dose achieved.&#xD;
&#xD;
      There are four separate periods of this study: Screening (signing of written informed consent&#xD;
      through Day -1), Treatment (for 26 weeks), Follow-up (additional 52 weeks), and Long-term&#xD;
      Follow-up (for additional 3 years). The first 3 periods will be considered the Core phase of&#xD;
      the study.&#xD;
&#xD;
      Study completion (Core) will occur when the last patient completes the 26-week treatment and&#xD;
      52-week Follow-up Period [at Week 78].&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 30, 2017</start_date>
  <completion_date type="Anticipated">April 9, 2025</completion_date>
  <primary_completion_date type="Actual">April 22, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Eltrombopag PK parameter: AUCtau</measure>
    <time_frame>2 weeks and 11 weeks after dose initiation</time_frame>
    <description>Area under the curve calculated to the end of the dosing interval (tau).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Eltrombopag PK parameter: Cmax</measure>
    <time_frame>2 weeks and 11 weeks after dose initiation</time_frame>
    <description>Peak concentration of drug</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Eltrombopag PK parameter: Ctrough</measure>
    <time_frame>2 weeks and 11 weeks after dose initiation</time_frame>
    <description>Pre-dose drug concentration in a repeated dose setting.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants who have achieved a complete (CR) or partial response (PR)</measure>
    <time_frame>Week 12, Week 26, Week 52, and Week 78.</time_frame>
    <description>Percentage of participants who have achieved a complete (CR) or partial response (PR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with a platelet response</measure>
    <time_frame>Week 12, Week 26, Week 52, and Week 78.</time_frame>
    <description>Percentage of participants who have achieved a complete or partial platelet response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematologic counts</measure>
    <time_frame>Week 12, Week 26, Week 52, Week 78, and then annually up to 3 years</time_frame>
    <description>Platelet (PLT), Hgb, and neutrophil counts</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Red Blood Cell (RBC) transfusion independence</measure>
    <time_frame>From date of first dose to approx. 3 years</time_frame>
    <description>Number and frequency of participants with RBC transfusion independence defined as a period of time of at least 56 days without RBC transfusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet transfusion independence</measure>
    <time_frame>From date of first dose to approx. 3 years</time_frame>
    <description>Number and frequency of participants with platelet transfusion independence defined as a period of time of at least 28 days without PLT transfusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone marrow cellularity</measure>
    <time_frame>Screening, Week 12, Week, 26, Week 52, Week 78 and then annually up to 3 years</time_frame>
    <description>Percentage of hematopoietic cells in bone marrow biopsy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone marrow morphology</measure>
    <time_frame>Screening, Week 12, Week, 26, Week 52, Week 78 and then annually up to 3 years</time_frame>
    <description>Percentage of hematopoietic cells in bone marrow aspirate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone marrow cytogenetics</measure>
    <time_frame>Screening, Week 12, Week, 26, Week 52, Week 78 and then annually up to 3 years</time_frame>
    <description>Chromosomal structure by karyotyping and Fluorescence in situ hybridization (FISH)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability and palatability for both tablets and powder for oral suspension</measure>
    <time_frame>Week 1, Week 2, Week 3, Week 4, Week, 12, Week 26, Week 78</time_frame>
    <description>Standardized (total) summary score, ranged from 0-100 will be derived from all items from the questionnaire based on a scoring matrix.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clonal evolution to Paroxysmal Nocturnal Hemoglobinuria (PNH)</measure>
    <time_frame>Baseline, Week 12, 26, 52, 78 and annually for up to 3 years to at time of disease progression.</time_frame>
    <description>Percentage of participants with PNH clones</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exposure-response relationship of eltrombopag and overall response and platelet response</measure>
    <time_frame>Week 12 or up to Week 26 when the PK highest dose has been achieved</time_frame>
    <description>Pharmacokinetic parameters of eltrombopag at the highest dose by the best overall response and platelet response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alternate Overall response (aOR)</measure>
    <time_frame>Week 12, Week 26, Week 52, and Week 78.</time_frame>
    <description>Percentage of participants with alternate overall response rate (aORR) defined as the proportion of patients who have achieved an alternate complete response (aCR) or an alternate partial response (aPR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK of eltrombopag at the starting dose (AUCtau)</measure>
    <time_frame>Week 3 Day 1</time_frame>
    <description>Pharmacokinetic parameters of eltrombopag (AUCtau)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK of eltrombopag at the starting dose (Cmax)</measure>
    <time_frame>Week 3 Day 1</time_frame>
    <description>Pharmacokinetic parameters of eltrombopag (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK of eltrombopag at the starting dose (Ctrough)</measure>
    <time_frame>Week 3 Day 1</time_frame>
    <description>Pharmacokinetic parameters of eltrombopag (Ctrough)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>Aplastic Anemia</condition>
  <arm_group>
    <arm_group_label>Cohort A (Option 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Regimen 1: hATG (ATGAM®), CsA and eltrombopag begin on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort A (option 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CsA and eltrombopag begin on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>previously untreated SAA), hATG (ATGAM®), CsA and eltrombopag begin on Day 1 and all patients will be treated with the same regimen</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eltrombopag</intervention_name>
    <description>Tablet for oral use, once daily or Powder for oral suspension (PfOS), once daily</description>
    <arm_group_label>Cohort A (Option 1)</arm_group_label>
    <arm_group_label>Cohort A (option 2)</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
    <other_name>ETB115</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>hATG</intervention_name>
    <description>Horse ATG (ATGAM) (hATG) is not considered an investigational medicinal product (IMP)</description>
    <arm_group_label>Cohort A (Option 1)</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CsA</intervention_name>
    <description>Cyclosporine (CsA) will be by supplied as either oral capsules or oral solution, administered twice a day</description>
    <arm_group_label>Cohort A (Option 1)</arm_group_label>
    <arm_group_label>Cohort A (option 2)</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For Cohort A patients:&#xD;
&#xD;
          1. History of prior diagnosis of SAA,&#xD;
&#xD;
          2. Diagnosis of relapsed/refractory SAA or recurrent AA following treatment for SAA, as&#xD;
             per Section 5.1. Patients with recurrent AA (e.g., losing their response) are exempt&#xD;
             from meeting the diagnostic criteria for SAA relapse at the time of study enrollment,&#xD;
             but must have been previously diagnosed with SAA.&#xD;
&#xD;
          3. Agree to concurrent eltrombopag treatment with appropriate, investigator-selected&#xD;
             Immunosuppressive therapy (IST) with either hATG + CsA or CsA.&#xD;
&#xD;
             For Cohort B patients:&#xD;
&#xD;
          4. Diagnosis of SAA at time of enrollment.&#xD;
&#xD;
          5. Patients must not have been previously treated with IST, and must meet all criteria as&#xD;
             described in Table 5-1.&#xD;
&#xD;
          6. Patients must agree to treatment with hATG + CsA concurrent with eltrombopag.&#xD;
&#xD;
             All patients eligible for inclusion in this study must meet all of the following&#xD;
             criteria:&#xD;
&#xD;
          7. Age 1 to &lt;18 years.&#xD;
&#xD;
          8. Assessments to rule out congenital/inherited bone marrow failure syndromes and other&#xD;
             causes of immune-mediated pancytopenia, which may be treated with transplant, must be&#xD;
             completed prior to enrollment.&#xD;
&#xD;
          9. Hematopoietic stem cell transplantation (HSCT) is not suitable or available as a&#xD;
             treatment option or has been refused by the patient. (Candidacy for HSCT will be&#xD;
             determined as per local practices or national guidelines.)&#xD;
&#xD;
         10. Bone marrow aspirate and biopsy at any time during the 4 weeks prior to first dose of&#xD;
             eltrombopag.&#xD;
&#xD;
        12. Performance status score: Karnofsky ≥50 for patients 16 years of age and older or&#xD;
        Lansky ≥50 for patients below 16 years of age.&#xD;
&#xD;
        15. Written informed consent must be signed by a parent or legal guardian prior to&#xD;
        initiation of any study specific procedure.&#xD;
&#xD;
        16. Normal karyotype within 4 weeks prior to first dose of eltrombopag. If there are&#xD;
        insufficient metaphases (&lt; 10) to determine karyotype, a repeat marrow aspirate is&#xD;
        required. If upon repeat bone marrow aspirate, the number of metaphases is insufficient (&lt;&#xD;
        10), then FISH probes performed in marrow aspirate as per protocol must be normal.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        2. Prior and/or active medical history of:&#xD;
&#xD;
          -  Fanconi anemia (via chromosome breakage test or growth arrest by flow cytometry)&#xD;
&#xD;
          -  Other known underlying inherited marrow failure syndrome (such as but not limited to&#xD;
             Dyskeratosis Congenita, Congenital Amegakaryocytic Thrombocytopenia, or&#xD;
             Shwachman-Diamond Syndrome).&#xD;
&#xD;
          -  Symptomatic Paroxysmal Nocturnal Hemoglobinuria (PNH) and/or PNH clones &gt;50% of White&#xD;
             blood cell (WBC) or Red blood cell (RBC) at time of enrollment.&#xD;
&#xD;
          -  Any cytogenetic abnormalities by karyotyping or FISH.&#xD;
&#xD;
          -  Myelodysplastic syndrome (MDS)&#xD;
&#xD;
          -  Other known or suspected underlying primary immunodeficiency&#xD;
&#xD;
          -  Any malignancy 3. Active infection not responding to appropriate therapy. 4. Prior&#xD;
             eltrombopag or other thrombopoietin receptor (TPO-R) agonist treatment for at least 2&#xD;
             months and a lack of response.&#xD;
&#xD;
             5. Have any of the following out-of-range laboratory values:&#xD;
&#xD;
          -  Serum Creatinine &gt;2.5 × upper limit of normal (ULN),&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &gt;3 × ULN. 6.&#xD;
             Concurrent participation in an investigational study within 30 days prior to&#xD;
             enrollment or within 5-half-lives of the investigational product, whichever is longer.&#xD;
             Note: a parallel enrollment in a registry for patients with SAA or AA is acceptable.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Phoenix Children's Hospital SC</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arkansas Childrens Hospital SC</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Childrens Hospital Colorado .</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aflac Cancer and Blood Disorders Center</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann and Robert H Lurie Childrens Hospital of Chicago SC</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University SC Riley Children's Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202-5225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Childrens Hospital of Boston SC</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Health System SC</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center SC-2</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center SC</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Cleveland Clinic (5)</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Children's Cancer and Hematology Center SC</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shatin</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lisboa</city>
        <zip>1649-035</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Moscow</city>
        <zip>117198</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197022</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bangkok noi</city>
        <state>Bangkok</state>
        <zip>10700</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Khon Kaen</city>
        <state>THA</state>
        <zip>40002</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bangkok</city>
        <zip>10400</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>London</city>
        <zip>WC1N 3JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
    <country>Portugal</country>
    <country>Russian Federation</country>
    <country>Thailand</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Netherlands</country>
  </removed_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 19, 2017</study_first_posted>
  <disposition_first_submitted>March 24, 2023</disposition_first_submitted>
  <disposition_first_submitted_qc>March 24, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">March 30, 2023</disposition_first_posted>
  <last_update_submitted>September 11, 2023</last_update_submitted>
  <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Eltrombopag</keyword>
  <keyword>Horse anti-thymocyte globulin</keyword>
  <keyword>Cyclosporine</keyword>
  <keyword>previously untreated or relapsed severe aplastic anemia</keyword>
  <keyword>recurrent aplastic anemia</keyword>
  <keyword>Severe aplastic anemia</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Immunosuppressive therapy</keyword>
  <keyword>ETB115</keyword>
  <keyword>Refractory</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Anemia, Aplastic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03025698
org study id: CETB115E2201
nct id: NCT03025698
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase II, open label, multi-center, intra-patient dose escalation study to
      characterize the pharmacokinetics (PK) after oral administration of eltrombopag in
      combination with immunosuppressive therapy in pediatric patients with previously untreated or
      relapsed/refractory severe aplastic anemia or recurrent aplastic anemia.
All patients will be treated with eltrombopag for the 26-week Treatment Period, followed by a
      52-week Follow-Up Period. Patients who have been previously untreated with immunosuppressive
      therapy will be treated according to the standard of care, hATG/cyclosporine, in addition to
      eltrombopag. Patients with relapsed/refractory SAA or recurrent AA will be enrolled into one
      of two treatment options: hATG/cyclosporine plus eltrombopag or cyclosporine plus
      eltrombopag, depending on prior treatment with immunosuppressive therapy.

      After initiating treatment with eltrombopag, patients will have their dose assessed and
      modified as tolerated, until the targeted platelet count or maximum dose is achieved.
      Pharmacokinetic assessments will be performed at time points intended to capture steady state
      PK of the starting dose and highest dose achieved.

      There are four separate periods of this study: Screening (signing of written informed consent
      through Day -1), Treatment (for 26 weeks), Follow-up (additional 52 weeks), and Long-term
      Follow-up (for additional 3 years). The first 3 periods will be considered the Core phase of
      the study.

      Study completion (Core) will occur when the last patient completes the 26-week treatment and
      52-week Follow-up Period [at Week 78].
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Eltrombopag PK parameter: AUCtau
time frame: 2 weeks and 11 weeks after dose initiation
description: Area under the curve calculated to the end of the dosing interval (tau).
measure: Eltrombopag PK parameter: Cmax
time frame: 2 weeks and 11 weeks after dose initiation
description: Peak concentration of drug
measure: Eltrombopag PK parameter: Ctrough
time frame: 2 weeks and 11 weeks after dose initiation
description: Pre-dose drug concentration in a repeated dose setting.
measure: Percentage of participants who have achieved a complete (CR) or partial response (PR)
time frame: Week 12, Week 26, Week 52, and Week 78.
description: Percentage of participants who have achieved a complete (CR) or partial response (PR)
measure: Percentage of participants with a platelet response
time frame: Week 12, Week 26, Week 52, and Week 78.
description: Percentage of participants who have achieved a complete or partial platelet response
measure: Hematologic counts
time frame: Week 12, Week 26, Week 52, Week 78, and then annually up to 3 years
description: Platelet (PLT), Hgb, and neutrophil counts
measure: Red Blood Cell (RBC) transfusion independence
time frame: From date of first dose to approx. 3 years
description: Number and frequency of participants with RBC transfusion independence defined as a period of time of at least 56 days without RBC transfusion.
measure: Platelet transfusion independence
time frame: From date of first dose to approx. 3 years
description: Number and frequency of participants with platelet transfusion independence defined as a period of time of at least 28 days without PLT transfusion.
measure: Bone marrow cellularity
time frame: Screening, Week 12, Week, 26, Week 52, Week 78 and then annually up to 3 years
description: Percentage of hematopoietic cells in bone marrow biopsy.
measure: Bone marrow morphology
time frame: Screening, Week 12, Week, 26, Week 52, Week 78 and then annually up to 3 years
description: Percentage of hematopoietic cells in bone marrow aspirate
measure: Bone marrow cytogenetics
time frame: Screening, Week 12, Week, 26, Week 52, Week 78 and then annually up to 3 years
description: Chromosomal structure by karyotyping and Fluorescence in situ hybridization (FISH)
measure: Acceptability and palatability for both tablets and powder for oral suspension
time frame: Week 1, Week 2, Week 3, Week 4, Week, 12, Week 26, Week 78
description: Standardized (total) summary score, ranged from 0-100 will be derived from all items from the questionnaire based on a scoring matrix.
measure: Clonal evolution to Paroxysmal Nocturnal Hemoglobinuria (PNH)
time frame: Baseline, Week 12, 26, 52, 78 and annually for up to 3 years to at time of disease progression.
description: Percentage of participants with PNH clones
measure: Exposure-response relationship of eltrombopag and overall response and platelet response
time frame: Week 12 or up to Week 26 when the PK highest dose has been achieved
description: Pharmacokinetic parameters of eltrombopag at the highest dose by the best overall response and platelet response
measure: Alternate Overall response (aOR)
time frame: Week 12, Week 26, Week 52, and Week 78.
description: Percentage of participants with alternate overall response rate (aORR) defined as the proportion of patients who have achieved an alternate complete response (aCR) or an alternate partial response (aPR)
measure: PK of eltrombopag at the starting dose (AUCtau)
time frame: Week 3 Day 1
description: Pharmacokinetic parameters of eltrombopag (AUCtau)
measure: PK of eltrombopag at the starting dose (Cmax)
time frame: Week 3 Day 1
description: Pharmacokinetic parameters of eltrombopag (Cmax)
measure: PK of eltrombopag at the starting dose (Ctrough)
time frame: Week 3 Day 1
description: Pharmacokinetic parameters of eltrombopag (Ctrough)
arm group label: Cohort A (Option 1)
arm group type: Experimental
description: Regimen 1: hATG (ATGAM®), CsA and eltrombopag begin on Day 1.
arm group label: Cohort A (option 2)
arm group type: Experimental
description: CsA and eltrombopag begin on Day 1.
arm group label: Cohort B
arm group type: Experimental
description: previously untreated SAA), hATG (ATGAM®), CsA and eltrombopag begin on Day 1 and all patients will be treated with the same regimen
intervention type: Drug
intervention name: Eltrombopag
description: Tablet for oral use, once daily or Powder for oral suspension (PfOS), once daily
arm group label: Cohort A (Option 1)
arm group label: Cohort A (option 2)
arm group label: Cohort B
other name: ETB115
intervention type: Drug
intervention name: hATG
description: Horse ATG (ATGAM) (hATG) is not considered an investigational medicinal product (IMP)
arm group label: Cohort A (Option 1)
arm group label: Cohort B
intervention type: Drug
intervention name: CsA
description: Cyclosporine (CsA) will be by supplied as either oral capsules or oral solution, administered twice a day
arm group label: Cohort A (Option 1)
arm group label: Cohort A (option 2)
arm group label: Cohort B
criteria: 
gender: All
minimum age: 1 Year
maximum age: 18 Years
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: Hong Kong
country: Portugal
country: Russian Federation
country: Thailand
country: United Kingdom
country: United States
country: Netherlands
responsible party type: Sponsor
mesh term: Anemia
mesh term: Anemia, Aplastic
sharing ipd: Undecided