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

NCT03025698 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CETB115E22012015-003166-91
• Study Type: interventional
• Target: 51
• Locations: 6 countries
• Sites: 20

Brief 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 recurrent aplastic anemia (AA).

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; ETB115; Refractory

Outcome Measures

Primary Outcomes (3)

• 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)

  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)

  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).

  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)

  Week 12, Week 26, Week 52, Week 78

• Hematologic Counts (Platelets (Blood), Neutrophils (Blood))

  Week 12, Week 26, Week 52, Week 78, Week 130, Week 182, Week 234

• Hematologic Counts (Hemoglobin (Blood))

  Week 12, Week 26, Week 52, Week 78, Week 130, Week 182, Week 234

• Number of Red Blood Cells (RBC) Transfusions

  From date of first dose to approx. 4.5 years

• Frequency of Red Blood Cell (RBC) Transfusions

  From date of first dose to approx. 4.5 years

Study Arms (3)

Cohort A (Option 1)

EXPERIMENTAL

hATG (ATGAM®), CsA and eltrombopag begin on Day 1.

Drug: Eltrombopag; Drug: hATG; Drug: CsA

Cohort A (option 2)

EXPERIMENTAL

CsA and eltrombopag begin on Day 1.

Drug: Eltrombopag; Drug: CsA

Cohort B

EXPERIMENTAL

hATG (ATGAM®), CsA and eltrombopag begin on Day 1.

Drug: Eltrombopag; Drug: hATG; Drug: CsA

Interventions

Eltrombopag DRUG

Tablet for oral use, once daily or Powder for oral suspension (PfOS), once daily

Also known as: ETB115

Cohort A (Option 1); Cohort A (option 2); Cohort B

hATG DRUG

Horse ATG (ATGAM) (hATG) is not considered an investigational medicinal product (IMP)

Cohort A (Option 1); Cohort B

CsA DRUG

Cyclosporine (CsA) was supplied as either oral capsules or oral solution, administered twice a day.

Cohort A (Option 1); Cohort A (option 2); Cohort B

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (20)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Childrens Hospital

Little Rock, Arkansas, 72202, United States

Location

Childrens Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Aflac Cancerand Blood Disorders Ctr

Atlanta, Georgia, 30342, United States

Location

Ann and Robert H Lurie Childs Hosp

Chicago, Illinois, 60611, United States

Location

Indiana University

Indianapolis, Indiana, 46202-5225, United States

Location

Childrens Hosp Boston Dept of Heme

Boston, Massachusetts, 02115, United States

Location

University of MI Health System

Ann Arbor, Michigan, 48109, United States

Location

Hackensack University Medical Center SC-2

Hackensack, New Jersey, 07601, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Texas Childrens Cancer and Hematology Center

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Hong Kong, 999077, Hong Kong

Location

Novartis Investigative Site

Lisbon, 1649-035, Portugal

Location

Novartis Investigative Site

Moscow, 117198, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197022, Russia

Location

Novartis Investigative Site

Khon Kaen, THA, 40002, Thailand

Location

Novartis Investigative Site

Bangkok, 10400, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

London, WC1N 3JH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 40315366 DERIVED

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-3000

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2017
• First Posted: January 19, 2017
• Study Start: September 30, 2017
• Primary Completion: April 22, 2022
• Study Completion: January 27, 2025
• Last Updated: August 10, 2026
• Results First Posted: August 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

US (12); RU (2); TH (3); HK (1); PT (1); GB (1)