Combination of Eltrombopag With Immunosuppressive Therapy in East-Asian Patients With Severe Aplastic Anemia

NCT04328727 | Completed Phase 2 Results

• 2 other identifiers: CETB115G22012024-000602-14
• Study Type: interventional
• Target: 36
• Locations: 4 countries
• Sites: 12

Brief Summary

This study was designed to evaluate the efficacy and safety of eltrombopag when added to r-ATG and CsA in treatment naive East-Asian adult and pediatric patients with severe aplastic anemia (SAA).

Conditions

Severe Aplastic Anemia (SAA)

Keywords

Treatment naïve severe aplastic anemia; SAA; eltrombopag; ETB115; immunosuppressive therapy; rabbit anti-thymocyte globulin; r-ATG; cyclosporine A; CsA; East-Asian patients

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate at Week 26

  Complete response rate was defined as percentage of patients achieving complete response (CR). Complete response was defined as subjects meeting all the three criteria on two consecutive serial blood count measurements at least one week apart but not more than four weeks apart: * Absolute neutrophil count \> 1.0 ×10\^9/L * Platelet count \> 100 ×10\^9/L * Hemoglobin \> 100 g/L The participants who discontinued from the trial before Week 26 and those that received blood products prior to response assessment (7 days prior for platelet transfusions, 14 days for RBC transfusion and 21 days for growth factors) were treated as non-responders.

  Week 26 (6 months after starting study treatment)

Secondary Outcomes (16)

• Complete Response (CR) Rate

  Week 13 (3 months), Week 52 (12 months) and yearly after up to 3 years

• Overall Response (ORR) Rate

  Week 13 (3 months), 26 weeks (6 months), 52 weeks and yearly after up to 3 years

• Duration of Complete Response

  Up to aproximately 3 years

• Duration of Overall Response

  Up to aproximately 3 years

• Overall Survival (OS)

  Up to approximately 3 years

Study Arms (1)

eltrombopag

EXPERIMENTAL

Participants received eltrombopag in combination with r-ATG and CsA. * Eltrombopag was administered orally once daily with initial doses of 75mg/day for ≥ 12 years old and 37.5 mg/day for participants between ≥ 6 and \< 12 years. Doses could be adjusted based on platelet count * r-ATG was administered intravenously at a dose of 2.5 to 3.5 mg/kg/day on Days 1-5 * CsA was administered orally every 12 h at a starting dose of 3-6 mg/kg/day

Drug: eltrombopag; Drug: rabbit anti-thymocyte globulin (r-ATG); Drug: cyclosporine A (CsA)

Interventions

eltrombopag DRUG

Tablet 25mg and 12.5mg

Also known as: ETB115

eltrombopag

rabbit anti-thymocyte globulin (r-ATG) DRUG

r-ATG 25 mg sterile lyophilized powder in 10 mL vials for IV use

Also known as: r-ATG

eltrombopag

cyclosporine A (CsA) DRUG

CsA 25mg Capsule or CsA 5.0g/50mL solution for oral use

Also known as: CsA

eltrombopag

Eligibility Criteria

• Age: 6 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written study informed consent and (where applicable) assent from the subject, parent, or guardian must be obtained prior to participation in the study.
• Subjects of East Asian ethnicity aged ≥ 6 years old at the time of written informed consent and assent form (if applicable).
• SAA characterized by:
• Bone marrow cellularity \< 25%, or 25-50% with \< 30% residual hematopoietic cells and pancytopenia, with at least two of the following parameters in peripheral blood:
• Absolute neutrophil count \< 0.5×109/L
• Platelet count \< 20×109/L
• Absolute reticulocyte count \< 20×109/L
• HSCT not suitable or available as a treatment option (determined as per local practices or national guidelines), or has been refused by subject.

You may not qualify if:

• Prior IST with any ATG/ALG , alemtuzumab, high dose cyclophosphamide (≥ 45 mg/kg/day), CsA within 6 months, or prior thrombopoietin receptor agonists.
• Eastern Cooperative Oncology Group (ECOG) performance status (age ≥ 16 years) \>2, or Lansky performance status (age \< 16 years) \<50.
• Prior and/or active medical history of:
• Known underlying congenital/inherited bone marrow failure or aplastic anemia (e.g.,such as but not limited to Fanconi anemia, congenital dyskeratosis, congenital amegakaryocytic thrombocytopenia, or Shwachman-Diamond Syndrome)
• Symptomatic paroxysmal nocturnal hemoglobinuria (PNH) and/or PNH clones \>50% of polymorphonuclear neutrophil (PMN) or RBC at time of enrollment
• Myelodysplastic syndrome (MDS)
• Any cytogenetic abnormalities on karyotyping or FISH within 30 days of study enrollment (an evaluable karyotyping with at least 10 metaphases is mandatory for eligibility)
• Other known or suspected underlying primary immunodeficiency
• Any concomitant malignancies that have not fully recovered from treatment or have not been disease-free for 5 years
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times the upper limit of normal (ULN).
• Creatinine ≥ 2.5×local ULN
• Past medical history of thromboembolism within 6 months, and/or prior or current antiphospholipid antibody syndrome (APS).
• Presence of clinically active uncontrolled significant (of such severity that it would preclude the subject's ability to consent, be compliant with study procedures, tolerate protocol therapy) infection, including bacterial, fungal, mycobacterial, parasitic or viral infection, or any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol
• Any severe and/or uncontrolled medical conditions which could cause unacceptable safety risks or compromise compliance with the protocol, such as:
• Known hepatocellular disease (e.g. active hepatitis or cirrhosis)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Guangzhou, Guangdong, 510000, China

Location

Novartis Investigative Site

Zhengzhou, Henan, 450052, China

Location

Novartis Investigative Site

Nanchang, Jiangxi, 330006, China

Location

Novartis Investigative Site

Changchun, Jilin, 130021, China

Location

Novartis Investigative Site

Tianjin, 300020, China

Location

Novartis Investigative Site

Tianjin, 300052, China

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 466 8560, Japan

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 812-8582, Japan

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104 8560, Japan

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 06351, South Korea

Location

Novartis Investigative Site

Kaohsiung City, 83301, Taiwan

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com
• A Pediatric Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

eltrombopag; Antilymphocyte Serum; Cyclosporine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 31, 2020
• Study Start: November 4, 2020
• Primary Completion: June 10, 2022
• Study Completion: December 6, 2024
• Last Updated: January 13, 2026
• Results First Posted: July 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

CN (6); JP (3); KR (2); TW (1)