Aplastic AnemiaPhase 2NCT03025698
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
A Phase 2 study testing Eltrombopag, hATG and CsA in people with Aplastic Anemia, run by Novartis Pharmaceuticals at 20 sites in 6 countries.
Trial summary
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 (SAA) or… Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Aplastic Anemia
- What is being tested?
- Eltrombopag, hATG and CsA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 20 sitesin 6 countries
- Study dates
- 30 Sep 2017to 27 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- For Cohort A patients:
- History of prior diagnosis of SAA,
- Diagnosis of relapsed/refractory SAA or recurrent AA following treatment for SAA, as per Section 5.1. Patients with recurrent AA (e.g., losing their response) are exempt from meeting the diagnostic criteria for SAA relapse at the time of study enrollment, but must have been previously diagnosed with SAA.
- Agree to concurrent eltrombopag treatment with appropriate, investigator-selected Immunosuppressive therapy (IST) with either hATG + CsA or CsA.
- For Cohort B patients:
- Diagnosis of SAA at time of enrollment.
Show all 16Show fewer
- Patients must not have been previously treated with IST, and must meet all criteria as described in Table 5-1.
- Patients must agree to treatment with hATG + CsA concurrent with eltrombopag.
- All patients eligible for inclusion in this study must meet all of the following criteria:
- Age 1 to <18 years.
- 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.
- Hematopoietic stem cell transplantation (HSCT) is not suitable or available as a treatment option or has been refused by the patient. (Candidacy for HSCT will be determined as per local practices or national guidelines.)
- Bone marrow aspirate and biopsy at any time during the 4 weeks prior to first dose of eltrombopag.
- Performance status score: Karnofsky ≥50 for patients 16 years of age and older or Lansky ≥50 for patients below 16 years of age.
- Written informed consent must be signed by a parent or legal guardian prior to initiation of any study specific procedure.
- Normal karyotype within 4 weeks prior to first dose of eltrombopag. If there are insufficient metaphases (< 10) to determine karyotype, a repeat marrow aspirate is required. If upon repeat bone marrow aspirate, the number of metaphases is insufficient (< 10), then FISH probes performed in marrow aspirate as per protocol must be normal.
Who cannot join
- 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)
Show all 30Show fewer
- 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).
Trial locations and contacts
20 sites in 6 countries.
20 sites in 6 countries
United States12 sites
University of MI Health System
Ann Arbor, Michigan, 48109
Aflac Cancerand Blood Disorders Ctr
Atlanta, Georgia, 30342
Childrens Hospital Colorado
Aurora, Colorado, 80045
Childrens Hosp Boston Dept of Heme
Boston, Massachusetts, 02115
Ann and Robert H Lurie Childs Hosp
Chicago, Illinois, 60611
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Duke University Medical Center
Durham, North Carolina, 27710
Hackensack University Medical Center SC-2
Hackensack, New Jersey, 07601
Texas Childrens Cancer and Hematology Center
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202-5225
Arkansas Childrens Hospital
Little Rock, Arkansas, 72202
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Thailand3 sites
Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Bangkok, 10700
Novartis Investigative Site
Khon Kaen, THA, 40002
Russia2 sites
Novartis Investigative Site
Moscow, 117198
Novartis Investigative Site
Saint Petersburg, 197022
About this study
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
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 (SAA) or recurrent aplastic anemia (AA).
Read the detailed description
All patients were treated with eltrombopag for the 26-week Treatment Period, followed by a 52-week Follow-Up Period. Patients who had been previously untreated with immunosuppressive therapy were treated according to the standard of care, hATG plus cyclosporine plus eltrombopag. Patients with relapsed/refractory SAA or recurrent AA were enrolled into one of two treatment options: hATG plus cyclosporine plus eltrombopag or cyclosporine plus eltrombopag, depending on prior treatment with immunosuppressive therapy. Patients could receive eltrombopag beyond 26 weeks if the investigator thought that the patient was still receiving clinical benefit from the drug.
After initiating treatment with eltrombopag, patients had their dose assessed and modified as tolerated, until the targeted platelet count or maximum dose was achieved. Pharmacokinetic assessments were 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 were 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].
- Conditions
- Aplastic Anemia
- Being tested
- Eltrombopag, hATG, CsA
- Keywords
- Eltrombopag, Horse anti-thymocyte globulin, Cyclosporine, previously untreated or relapsed severe aplastic anemia, recurrent aplastic anemia, Severe aplastic anemia, Pharmacokinetics, Immunosuppressive therapy, ETB115, Refractory
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EltrombopagDrug
Also called ETB115
Tablet for oral use, once daily or Powder for oral suspension (PfOS), once daily
hATGDrug
Horse ATG (ATGAM) (hATG) is not considered an investigational medicinal product (IMP)
CsADrug
Cyclosporine (CsA) was supplied as either oral capsules or oral solution, administered twice a day.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A (Option 1) | Experimental | hATG (ATGAM®), CsA and eltrombopag begin on Day 1. Receives: Drug: Eltrombopag; Drug: hATG; Drug: CsA |
| Cohort A (option 2) | Experimental | CsA and eltrombopag begin on Day 1. Receives: Drug: Eltrombopag; Drug: CsA |
| Cohort B | Experimental | hATG (ATGAM®), CsA and eltrombopag begin on Day 1. Receives: Drug: Eltrombopag; Drug: hATG; Drug: CsA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Eltrombopag PK Parameters: AUCtau, AUClast
AUC tau: Area under the curve calculated to the end of the dosing interval ( tau) (mass*time/volume) AUC last: Area under the curve calculated to the last quantifiable concentration point (Tlast) (mass*time/volume)
Measured: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Eltrombopag PK Parameter: Cmax
Cmax is the observed maximum plasma concentration following administration (mass/volume)
Measured: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Eltrombopag PK Parameter: Ctrough at the Highest Dose Level
Ctrough is the pre-dose plasma concentration (mass/volume).
Measured: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Secondary outcomes (24)
Percentage of Participants With an Overall Response Rate and Percentage of Participants With a Platelet Response Rate Based on Per Pediatric Committee of European Medicines Agency (PDCO)
Overall response rate (ORR) is defined as the percentage of participants who have achieved a complete response (CR) or partial response (PR) or No response (NR) by the Investigator. CR criteria: Platelet (PLT) and red blood cell (RBC) transfusion independence, Normal age-adjusted Hgb, PLT >100 × 10^9/L and absolute neutrophil count (ANC) >1.5 × 10^9/L. PR: PLT and RBC Transfusion independence and at least 2 of the following criteria: Reticulocytes >30 × 10^9/L, PLT >30 × 10^9/L, ANC >1.5 x 10^9L. PLT transfusion independence is defined as a period for at least 28 days without PLT transfusion. Platelet response rate (PRR): Platelet response rate is comprised of CR + PR based on the following criteria: CR: PLT >100 × 10^9/L; PR: PLT >30 × 10^9/L; NR: PLT transfusion within 4 weeks or PLT <= 30 × 10^9/L.
Measured: Week 12, Week 26, Week 52, Week 78
Hematologic Counts (Platelets (Blood), Neutrophils (Blood))
Individual Platelets (PLT) and neutrophil counts were summarized for all participants.
Measured: Week 12, Week 26, Week 52, Week 78, Week 130, Week 182, Week 234
Hematologic Counts (Hemoglobin (Blood))
Individual hemoglobin (Hgb) counts were summarized for all participants.
Measured: Week 12, Week 26, Week 52, Week 78, Week 130, Week 182, Week 234
Number of Red Blood Cells (RBC) Transfusions
Number of transfusions during the treatment period refers to total number of RBC transfusions participants have received while on treatment.
Measured: From date of first dose to approx. 4.5 years
Frequency of Red Blood Cell (RBC) Transfusions
Frequency of transfusions during the treatment period refers to number of RBC transfusions during the treatment period divided by number of months of treatment duration.
Measured: From date of first dose to approx. 4.5 years
Number of Platelet (PLT) Transfusions
Number of transfusions during the treatment period refers to total number of PLT transfusions participants have received while on treatment.
Measured: From date of first dose to approx. 4.5 years
Frequency of Platelet (PLT) Transfusions
Frequency of transfusions during the treatment period refers to number of PLT transfusions during the treatment period divided by number of months of treatment duration.
Measured: From date of first dose to approx. 4.5 years
Total Duration of Red Blood Cell (RBC) Transfusion Independence During the Treatment Period
RBC transfusion independence is defined as a period of time of at least 56 days without RBC transfusion. Duration of RBC transfusion independence is defined as a period of time of at least 56 days without RBC transfusion. First transfusion duration was calculated as the date of the day before the first transfusion after baseline minus the date of first exposure eltrombopag + 1.
Measured: From date of first dose to approx. 4.5 years
Total Duration of Platelet (PLT) Transfusion Independence During the Treatment Period
Platelet transfusion independence during the treatment period is defined as the duration from the first day of the 28-day period without PLT transfusion until the occurrence of a PLT transfusion after the period free from any PLT transfusion. Duration of PLT transfusion independence is defined as a period of time of at least 28 days without platelet transfusion. First transfusion duration was calculated as the date of the day before the first transfusion after baseline minus the date of first exposure eltrombopag + 1.
Measured: From date of first dose to approx. 4.5 years
Maximum Duration of Red Blood Cell (RBC) Transfusion Independence
RBC transfusion independence is defined as a period of time of at least 56 days without RBC transfusion. Maximum duration of RBC transfusion independence is defined as the maximum duration among the durations of RBC transfusion independence. First transfusion duration was calculated as the date of first transfusion after baseline minus the date of first exposure eltrombopag + 1.
Measured: From date of first dose to approx. 4.5 years
Maximum Duration of Platelet (PLT) Transfusion Independence
Maximum duration of PLT transfusion independence is defined as the maximum duration among the durations of PLT transfusion independence. First transfusion duration was calculated as the date of first transfusion after baseline minus the date of first exposure eltrombopag + 1.
Measured: From date of first dose to approx. 4.5 years
Overall Bone Marrow Cellularity
Percentage of cells in bone marrow biopsy - a comprehensive diagnostic evaluation to distinguish between the various bone marrow disorders.
Measured: Screening, Week 26, Week 52, Week 78, Week 130, Week 182, Week 234
Bone Marrow Morphology
Percentage of morphology (erythropoiesis, granulopoiesis, megakaryopoiesis, CD34+ (blast cells) cells in bone marrow aspirate - a comprehensive diagnostic evaluation to distinguish between the various bone marrow disorders.
Measured: Screening, Week, 26, Week 52, Week 78, Week 130, Week 182, Week 234
Bone Marrow Cytogenetics
Number of bone marrow cytogenetics (chromosomal structure) by kryotyping and Fluorescence in situ hybridization (FISH). This is a comprehensive diagnostic evaluation to distinguish between the various bone marrow disorders.
Measured: Screening, Week 12, Week 26, Week 52, Week 78, Week 130, Week 182, Week 234
Acceptability and Palatability for Both Tablets and Powder Formulation for Oral Solution (PfOS)
Standardized (total) summary score, ranged from 0-100, (where 0 means worst and 100 means the best), was derived from all items from the questionnaire based on a scoring matrix. The questionnaire was completed by parents and caregivers of patients under 12 years of age (ObsRO) and a questionnaire completed by patients 12 years and older (PRO).
Measured: any day from Day 1 of drug initiation up to Week 78
Clonal Evolution to Paroxysmal Nocturnal Hemoglobinuria (PNH)
Percentage of participants with clonal evolution to Paroxysmal Nocturnal Hemoglobinuria (PNH).
Measured: Baseline, Week (W) 26 Day (D) 1, W52D1, W78D1, W130D1, W182D1, W234D1
Exposure (AUCtau) - Response Relationship of Eltrombopag and Best Overall Response Rate by Age Groups
Pharmacokinetic parameter (AUCtau) of eltrombopag at the highest dose in relationship to best overall response rate in regard to complete response (CR), partial response (PR) and no response (NR). AUC tau: Area under the curve calculated to the end of the dosing interval (tau) (mass*time/volume)
Measured: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Exposure (Cmax, Ctrough) - Response Relationship of Eltrombopag and Best Overall Response Rate by Age Groups
Pharmacokinetic parameters (Cmax and Ctrough) of eltrombopag at the highest dose in relationship to overall response rate in regard to complete response (CR), partial response (PR) and no response (NR). Cmax is the observed maximum plasma concentration following administration (mass/volume). Ctrough is the pre-dose plasma concentration (mass/volume).
Measured: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Exposure (AUCtau) - Response Relationship of Eltrombopag and Best Platelet Response Rate by Age Groups
Pharmacokinetic parameter (AUCtau) of eltrombopag at the highest dose in relationship to platelet response rate. AUC tau: Area under the curve calculated to the end of the dosing interval ( tau) (mass*time/volume)
Measured: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Exposure (Cmax, Ctrough) - Response Relationship of Eltrombopag and Best Platelet Response Rate by Age Groups
Pharmacokinetic parameters (Cmax and Ctrough) of eltrombopag at the highest dose in relationship to platelet response rate. Cmax is the observed maximum plasma concentration following administration (mass/volume). Ctrough is the pre-dose plasma concentration (mass/volume).
Measured: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Alternate Overall Response Rate (aORR)
Alternate overall responses were derived using hematological parameters (i.e., hemoglobin, platelet, reticulocyte, and ANC). aORR is defined as the percentage of participants who achieved an alternate complete response (aCR) or an alternate partial response (aPR)
Measured: Week 12, Week 26, Week 52, Week 78
Pharmacokinetics (PK) of Eltrombopag at the Starting Dose (AUCtau)
PK parameter, AUCtau. AUC tau: Area under the curve calculated to the end of the dosing interval (tau) (mass*time/volume)
Measured: Week 3 Day 1
PK of Eltrombopag at the Starting Dose (Cmax)
PK parameter, Cmax Cmax is the observed maximum plasma concentration following administration (mass/volume)
Measured: Week 3 Day 1
PK of Eltrombopag at the Starting Dose (Ctrough)
PK parameter, Ctrough Ctrough is the pre-dose plasma concentration (mass/volume).
Measured: Week 3 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2017 (estimated)
- Study start30 Sep 2017
- Primary completion22 Apr 2022
- Study completion27 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03025698
- Sponsor's protocol ID
- CETB115E2201
- Other IDs
- 2015-003166-91, 2015
- Status last verified
- Jul 2026
- First submitted
- 12 Jan 2017
- Last updated
- 10 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided are anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Shimamura A, Maschan A, Bennett C, Samarasinghe S, Farrar JE, Li CK, Sirachainan N, Pongtanakul B, Komvilaisak P, Zubarovskaya L, Rothman JA, Walkovich K, Nakano TA, Bertuch AA, Ferrao A, Bhat R, Hanna R, Overholt K, Boklan J, Wong TF, Wang Q, Urban P, Strahm B, Wang W, Vlachos A, Williams DA. Eltrombopag in combination with immunosuppressive therapy in pediatric severe aplastic anemia: phase 2 ESCALATE trial. Blood Adv. 2025 Aug 12;9(15):3728-3738. doi: 10.1182/bloodadvances.2024015102.
PubMed 40315366
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03025698
- Acronym / sponsor ID
- CETB115E2201
- Conditions
- Aplastic Anemia
- Keywords
- Eltrombopag, Horse anti-thymocyte globulin, Cyclosporine, previously untreated or relapsed severe aplastic anemia, recurrent aplastic anemia, Severe aplastic anemia, Pharmacokinetics, Immunosuppressive therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Sep 2017 (actual)
- Primary completion
- 22 Apr 2022 (actual)
- Study completion
- 27 Jan 2025 (actual)
- First posted
- 19 Jan 2017 (estimated)
- Results
- Posted 10 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (SAA) or recurrent aplastic anemia (AA).
Detailed description
All patients were treated with eltrombopag for the 26-week Treatment Period, followed by a 52-week Follow-Up Period. Patients who had been previously untreated with immunosuppressive therapy were treated according to the standard of care, hATG plus cyclosporine plus eltrombopag. Patients with relapsed/refractory SAA or recurrent AA were enrolled into one of two treatment options: hATG plus cyclosporine plus eltrombopag or cyclosporine plus eltrombopag, depending on prior treatment with immunosuppressive therapy. Patients could receive eltrombopag beyond 26 weeks if the investigator thought that the patient was still receiving clinical benefit from the drug.
After initiating treatment with eltrombopag, patients had their dose assessed and modified as tolerated, until the targeted platelet count or maximum dose was achieved. Pharmacokinetic assessments were 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 were 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].
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A (Option 1) | Experimental | Drug: Eltrombopag, Drug: hATG, Drug: CsAhATG (ATGAM®), CsA and eltrombopag begin on Day 1. |
| Cohort A (option 2) | Experimental | Drug: Eltrombopag, Drug: CsACsA and eltrombopag begin on Day 1. |
| Cohort B | Experimental | Drug: Eltrombopag, Drug: hATG, Drug: CsAhATG (ATGAM®), CsA and eltrombopag begin on Day 1. |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- History of prior diagnosis of SAA,
- Diagnosis of relapsed/refractory SAA or recurrent AA following treatment for SAA, as per Section 5.1. Patients with recurrent AA (e.g., losing their response) are exempt from meeting the diagnostic criteria for SAA relapse at the time of study enrollment, but must have been previously diagnosed with SAA.
- Agree to concurrent eltrombopag treatment with appropriate, investigator-selected Immunosuppressive therapy (IST) with either hATG + CsA or CsA.
- Diagnosis of SAA at time of enrollment.
- Patients must not have been previously treated with IST, and must meet all criteria as described in Table 5-1.
Key exclusion criteria (30 listed)
- Prior and/or active medical history of:
- Symptomatic Paroxysmal Nocturnal Hemoglobinuria (PNH) and/or PNH clones >50% of White blood cell (WBC) or Red blood cell (RBC) at time of enrollment.
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EltrombopagAlso: ETB115Tablet for oral use, once daily or Powder for oral suspension (PfOS), once daily | Drug | Cohort A (Option 1), Cohort A (option 2), Cohort B |
| hATGHorse ATG (ATGAM) (hATG) is not considered an investigational medicinal product (IMP) | Drug | Cohort A (Option 1), Cohort B |
| CsACyclosporine (CsA) was supplied as either oral capsules or oral solution, administered twice a day. | Drug | Cohort A (Option 1), Cohort A (option 2), Cohort B |
Primary outcome
Eltrombopag PK Parameters: AUCtau, AUClast
Time frame: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
AUC tau: Area under the curve calculated to the end of the dosing interval ( tau) (mass*time/volume) AUC last: Area under the curve calculated to the last quantifiable concentration point (Tlast) (mass*time/volume)
Eltrombopag PK Parameter: Cmax
Time frame: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Cmax is the observed maximum plasma concentration following administration (mass/volume)
Eltrombopag PK Parameter: Ctrough at the Highest Dose Level
Time frame: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Ctrough is the pre-dose plasma concentration (mass/volume).
24 secondary outcomes
Percentage of Participants With an Overall Response Rate and Percentage of Participants With a Platelet Response Rate Based on Per Pediatric Committee of European Medicines Agency (PDCO)
Time frame: Week 12, Week 26, Week 52, Week 78
Hematologic Counts (Platelets (Blood), Neutrophils (Blood))
Time frame: Week 12, Week 26, Week 52, Week 78, Week 130, Week 182, Week 234
Hematologic Counts (Hemoglobin (Blood))
Time frame: Week 12, Week 26, Week 52, Week 78, Week 130, Week 182, Week 234
Number of Red Blood Cells (RBC) Transfusions
Time frame: From date of first dose to approx. 4.5 years
Frequency of Red Blood Cell (RBC) Transfusions
Time frame: From date of first dose to approx. 4.5 years
Number of Platelet (PLT) Transfusions
Time frame: From date of first dose to approx. 4.5 years
Frequency of Platelet (PLT) Transfusions
Time frame: From date of first dose to approx. 4.5 years
Total Duration of Red Blood Cell (RBC) Transfusion Independence During the Treatment Period
Time frame: From date of first dose to approx. 4.5 years
Total Duration of Platelet (PLT) Transfusion Independence During the Treatment Period
Time frame: From date of first dose to approx. 4.5 years
Maximum Duration of Red Blood Cell (RBC) Transfusion Independence
Time frame: From date of first dose to approx. 4.5 years
Maximum Duration of Platelet (PLT) Transfusion Independence
Time frame: From date of first dose to approx. 4.5 years
Overall Bone Marrow Cellularity
Time frame: Screening, Week 26, Week 52, Week 78, Week 130, Week 182, Week 234
Bone Marrow Morphology
Time frame: Screening, Week, 26, Week 52, Week 78, Week 130, Week 182, Week 234
Bone Marrow Cytogenetics
Time frame: Screening, Week 12, Week 26, Week 52, Week 78, Week 130, Week 182, Week 234
Acceptability and Palatability for Both Tablets and Powder Formulation for Oral Solution (PfOS)
Time frame: any day from Day 1 of drug initiation up to Week 78
Clonal Evolution to Paroxysmal Nocturnal Hemoglobinuria (PNH)
Time frame: Baseline, Week (W) 26 Day (D) 1, W52D1, W78D1, W130D1, W182D1, W234D1
Exposure (AUCtau) - Response Relationship of Eltrombopag and Best Overall Response Rate by Age Groups
Time frame: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Exposure (Cmax, Ctrough) - Response Relationship of Eltrombopag and Best Overall Response Rate by Age Groups
Time frame: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Exposure (AUCtau) - Response Relationship of Eltrombopag and Best Platelet Response Rate by Age Groups
Time frame: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Exposure (Cmax, Ctrough) - Response Relationship of Eltrombopag and Best Platelet Response Rate by Age Groups
Time frame: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78
Alternate Overall Response Rate (aORR)
Time frame: Week 12, Week 26, Week 52, Week 78
Pharmacokinetics (PK) of Eltrombopag at the Starting Dose (AUCtau)
Time frame: Week 3 Day 1
PK of Eltrombopag at the Starting Dose (Cmax)
Time frame: Week 3 Day 1
PK of Eltrombopag at the Starting Dose (Ctrough)
Time frame: Week 3 Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40315366Shimamura A, Maschan A, Bennett C, Samarasinghe S, Farrar JE, Li CK, Sirachainan N, Pongtanakul B, Komvilaisak P, Zubarovskaya L, Rothman JA, Walkovich K, Nakano TA, Bertuch AA, Ferrao A, Bhat R, Hanna R, Overholt K, Boklan J, Wong TF, Wang Q, Urban P, Strahm B, Wang W, Vlachos A, Williams DA. Eltrombopag in combination with immunosuppressive therapy in pediatric severe aplastic anemia: phase 2 ESCALATE trial. Blood Adv. 2025 Aug 12;9(15):3728-3738. doi: 10.1182/bloodadvances.2024015102.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided are anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
20 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eltrombopag, hATG and CsA in people with Aplastic Anemia, run by Novartis Pharmaceuticals at 20 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Thailand, Russia, Hong Kong, Portugal and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Eltrombopag PK Parameters: AUCtau, AUClast (time frame: at least 11 weeks after dose initiation or later when patients are taking the highest dose, up to Week 78). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03025698, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.