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

NCT ID: NCT04328727

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-04
• Study Completion Date: 2024-12-06

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).

Detailed Description

This was a non-randomized, open label, single arm, multi-center, Phase II study to evaluate the efficacy and safety of eltrombopag in combination with immunosuppressive therapy (IST) regimen of r-ATG + CsA in East-Asian patients with severe aplatsic anemia who had not received prior IST.

Eligible participants were enrolled into the study and received eltrombopag (from Day 1 to Week 26) concomitantly with r-ATG (on Days 1-5) and CsA (from Day 1 to Week 26) in the core treatment part.

Participants who were assessed as responders (meeting complete (CR) or partial (PR) response criteria) at Week 26 were eligible for the extension part of the study and continued treatment with eltrombopag and CsA after Week 26 up to Week 52. During the extension part, eltrombopag treatment was provided up to Week 52. CsA was maintained or tapered at the investigator's discretion according to local practice, with a total duration of at least 2 years (18 months after Week 26). There was a 30 days after end of treatment safety follow-up at the end of the extension part.

All participants were offered to enter the long term follow-up after the discontinuation of eltrombopag, with yearly efficacy and clonal evolution assessments up to Year 3 (Week 156).

Conditions

Severe Aplastic Anemia (SAA)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

eltrombopag

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

Group Type: EXPERIMENTAL

eltrombopag

Intervention Type: DRUG

Tablet 25mg and 12.5mg

rabbit anti-thymocyte globulin (r-ATG)

Intervention Type: DRUG

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

cyclosporine A (CsA)

Intervention Type: DRUG

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

Interventions

eltrombopag

Tablet 25mg and 12.5mg

Intervention Type: DRUG

rabbit anti-thymocyte globulin (r-ATG)

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

Intervention Type: DRUG

cyclosporine A (CsA)

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

Intervention Type: DRUG

Other Intervention Names

ETB115; r-ATG; CsA

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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)
• Impairment of gastrointestinal (GI) function or gastrointestinal disease that may significantly alter the absorption of study treatment (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
• Active skin, mucosa, ocular or GI disorders of Grade > 1
• Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at screening. A positive serology for Hepatitis B (HB) is considered as a positive test for HBsAg. In addition, if serology is negative for HBsAg but hepatitis B core antibody (HBcAb) is positive (regardless of hepatitis B surface antibody (HBsAb) status), a hepatitis B virus (HBV) DNA test will be performed and if positive the patient will be excluded.
• Cardiac disorder (subjects with congestive heart disease of New York Heart Association (NYHA) functional classification Grade II/III/IV (for pediatric subjects, refer to the Grade II/III/IV of Modified ross heart failure classification for Children) should not be enrolled; subjects with NYHA Grade II due to cardiac disorder should not be enrolled but those with NYHA Grade II due to aplastic anemia (AA) may be enrolled.), arrhythmia with a risk of thrombosis (e.g. atrial fibrillation), pulmonary hypertension, or uncontrolled hypertension (>180/100 mmHg).

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Guangzhou, Guangdong, China

Novartis Investigative Site

Zhengzhou, Henan, China

Novartis Investigative Site

Nanchang, Jiangxi, China

Novartis Investigative Site

Changchun, Jilin, China

Novartis Investigative Site

Tianjin, , China

Novartis Investigative Site

Tianjin, , China

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Fukuoka, Fukuoka, Japan

Novartis Investigative Site

Chuo Ku, Tokyo, Japan

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Kaohsiung City, , Taiwan

Countries

China; Japan; South Korea; Taiwan

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2649

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

https://www.novctrd.com/ctrdweb/ppatientsummary/ppatientsummaries?periodicPatientSummaryId=700

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

Other Identifiers

2024-000602-14

Identifier Type: REGISTRY

Identifier Source: secondary_id

CETB115G2201

Identifier Type: -

Identifier Source: org_study_id