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Study to Assess the Safety and Efficacy of Eltrombopag in Chinese Refractory or Relapsed Severe Aplastic Anemia (SAA) Subjects.

Primary Purpose

Aplastic Anemia

Status

Completed

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Eltrombopag 25 mg

About this trial

This is an interventional treatment trial for Aplastic Anemia focused on measuring Severe Aplastic Anemia, Eltrombopag, ETB115, Chinese subject, Chinese refractory or relapsed SAA subjects, refractory severe aplastic anemia, relapsed severe aplastic anemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Chinese patients aged greater than or equal to 18 years old.
Patient with a previous diagnosis of severe aplastic anemia and had insufficient response following at least one treatment course in the period time of > 6 months of immunosuppression with a regimen containing anti-thymocyte globulin (ATG), anti-lymphocyte globulin (ALG), and/or cyclophosphamide, or alemtuzumab.
Platelet count ≤ 30 × 10^9/L at screening.
Patient must not currently have the option of stem cell transplantation.
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Patient with QTcF (Fridericia's QT correction formula) at screening <450 msec, or <480 msec with bundle branch block, as determined via the mean of a triplicate ECG and assessed at site.

Exclusion Criteria:

Treatment with ATG/ALG, cyclophosphamide or alemtuzumab in the past 6 months.
Congenital aplastic anemia
AST or ALT ≥3 times the upper limit of normal.
Creatinine, total bilirubin, and alkaline phosphatase (ALP) ≥ 1.5× local ULN (total bilirubin ≥ 2.5 × local ULN with Gilbert's Syndrome).
Paroxysmal nocturnal hemoglobinuria (PNH) granulocyte clone size determined by flow cytometry ≥ 50%.
Presence of chromosomal aberration (-7/7q- detected by fluorescence in situ hybridization (FISH), or other aberrations detected by G-band staining).
Evidence of a clonal hematologic bone marrow disorder on cytogenetics.
Past medical history of thromboembolism within 6 months or current use of anticoagulants.
Have any concomitant malignancies and must be fully recovered from treatment for any other malignancy and have been disease-free for 5 years.
Patient with clinically significant.
Patient with known hepatocellular disease
Presences of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening.
Cardiac disorder (NYHA) functional classification Grade II/III/IV
Past medical history of immediate or delayed hypersensitivity to compounds chemically similar to eltrombopag or their excipients.
Treatment with another investigational product within 30 days.
Prior treatment with eltrombopag, romiplostim, or any other TPO (thrombopoietin) receptor agonist.
Positive result for HIV (Human Immunodeficiency Virus) antibody test.
Pregnant or nursing (lactating) woman.
Woman of child-bearing potential.

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Eltrombopag

Arm Description

Subjects will start eltrombopag treatment at 25 mg/day since Day 1.

Outcomes

Primary Outcome Measures

Hematologic response rate

Hematologic response rate is defined as the percentage of all subjects who meet any of the IWG criteria (International Working Group).

Secondary Outcome Measures

Hematologic response rate

Hematologic response rate is defined as the percentage of all subjects who meet any of the IWG criteria (International Working Group).

Changes in platelet count

Changes in platelet count in the absence of platelet transfusion.

Changes in hemoglobin count

Changes in hemoglobin in the absence of RBC (Red Blood Cell) transfusion.

Changes in neutrophil count

Changes in neutrophil count in the absence of G-CSF (Granulocyte Colony Stimulating Factor).

Time to hematologic response

Time to hematologic response (any response according to the response criteria for the primary endpoint).

Duration of hematologic response

Duration of hematologic response (any response according to the response criteria for the primary endpoint).

Frequency of transfusion

Frequency of transfusion (platelet and RBC (Red Blood Cell))

Volume of transfusion

Volume of transfusion (platelet and RBC (Red Blood Cell))

Plasma concentration of eltrombopag including the trough concentrations

Plasma concentration of eltrombopag including the trough.

Rate of clonal evolution

Rate of clonal evolution including clonal evolution to PNH (Paroxysmal Nocturnal Hemoglobinuria), evolution to AML (Acute Myeloid Leukemia) or MDS (Myelodysplastic Syndromes).

Full Information

NCT ID

NCT03988608

First Posted

June 13, 2019

Last Updated

June 23, 2023

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03988608

Brief Title

Study to Assess the Safety and Efficacy of Eltrombopag in Chinese Refractory or Relapsed Severe Aplastic Anemia (SAA) Subjects.

Official Title

A Non-randomized, Open-label, Multi-center, Phase II Study to Assess the Safety and Efficacy of Eltrombopag in Chinese Subjects With Refractory or Relapsed Severe Aplastic Anemia

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

December 9, 2019 (Actual)

Primary Completion Date

July 16, 2021 (Actual)

Study Completion Date

May 17, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a non-randomized, open-label, phase II study to assess the efficacy and safety of eltrombopag in Chinese subjects with refractory or relapsed severe aplastic anemia (SAA). Treatment with eltrombopag will be started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day. The hematological response rate will be assessed at 3, 6 months and 1 year after starting the study treatment (Week 13, 26 and 52).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Aplastic Anemia

Keywords

Severe Aplastic Anemia, Eltrombopag, ETB115, Chinese subject, Chinese refractory or relapsed SAA subjects, refractory severe aplastic anemia, relapsed severe aplastic anemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Eltrombopag

Arm Type

Experimental

Arm Description

Subjects will start eltrombopag treatment at 25 mg/day since Day 1.

Intervention Type

Drug

Intervention Name(s)

Eltrombopag 25 mg

Other Intervention Name(s)

ETB115

Intervention Description

film-coated tablets containing 25 mg of eltrombopag free acid in each tablet

Primary Outcome Measure Information:

Title

Hematologic response rate

Description

Hematologic response rate is defined as the percentage of all subjects who meet any of the IWG criteria (International Working Group).

Time Frame

6 months (Week 26)

Secondary Outcome Measure Information:

Title

Hematologic response rate

Description

Hematologic response rate is defined as the percentage of all subjects who meet any of the IWG criteria (International Working Group).

Time Frame

Week 13 and Week 52

Title

Changes in platelet count

Description

Changes in platelet count in the absence of platelet transfusion.

Time Frame

Baseline to Week 26 or up to 3.5 years

Title

Changes in hemoglobin count

Description

Changes in hemoglobin in the absence of RBC (Red Blood Cell) transfusion.

Time Frame

Baseline to Week 26 or up to 3.5 years

Title

Changes in neutrophil count

Description

Changes in neutrophil count in the absence of G-CSF (Granulocyte Colony Stimulating Factor).

Time Frame

Baseline to Week 26 or up to 3.5 years

Title

Time to hematologic response

Description

Time to hematologic response (any response according to the response criteria for the primary endpoint).

Time Frame

Baseline to Week 26 or up to 3.5 years

Title

Duration of hematologic response

Description

Duration of hematologic response (any response according to the response criteria for the primary endpoint).

Time Frame

Baseline to Week 26 or up to 3.5 years

Title

Frequency of transfusion

Description

Frequency of transfusion (platelet and RBC (Red Blood Cell))

Time Frame

Baseline to Week 26 or up to 3.5 years

Title

Volume of transfusion

Description

Volume of transfusion (platelet and RBC (Red Blood Cell))

Time Frame

Baseline to Week 26 or up to 3.5 years

Title

Plasma concentration of eltrombopag including the trough concentrations

Description

Plasma concentration of eltrombopag including the trough.

Time Frame

Baseline to Week 26

Title

Rate of clonal evolution

Description

Rate of clonal evolution including clonal evolution to PNH (Paroxysmal Nocturnal Hemoglobinuria), evolution to AML (Acute Myeloid Leukemia) or MDS (Myelodysplastic Syndromes).

Time Frame

Baseline to Week 26 or up to 3.5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Chinese patients aged greater than or equal to 18 years old. Patient with a previous diagnosis of severe aplastic anemia and had insufficient response following at least one treatment course in the period time of > 6 months of immunosuppression with a regimen containing anti-thymocyte globulin (ATG), anti-lymphocyte globulin (ALG), and/or cyclophosphamide, or alemtuzumab. Platelet count ≤ 30 × 10^9/L at screening. Patient must not currently have the option of stem cell transplantation. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Patient with QTcF (Fridericia's QT correction formula) at screening <450 msec, or <480 msec with bundle branch block, as determined via the mean of a triplicate ECG and assessed at site. Exclusion Criteria: Treatment with ATG/ALG, cyclophosphamide or alemtuzumab in the past 6 months. Congenital aplastic anemia AST or ALT ≥3 times the upper limit of normal. Creatinine, total bilirubin, and alkaline phosphatase (ALP) ≥ 1.5× local ULN (total bilirubin ≥ 2.5 × local ULN with Gilbert's Syndrome). Paroxysmal nocturnal hemoglobinuria (PNH) granulocyte clone size determined by flow cytometry ≥ 50%. Presence of chromosomal aberration (-7/7q- detected by fluorescence in situ hybridization (FISH), or other aberrations detected by G-band staining). Evidence of a clonal hematologic bone marrow disorder on cytogenetics. Past medical history of thromboembolism within 6 months or current use of anticoagulants. Have any concomitant malignancies and must be fully recovered from treatment for any other malignancy and have been disease-free for 5 years. Patient with clinically significant. Patient with known hepatocellular disease Presences of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening. Cardiac disorder (NYHA) functional classification Grade II/III/IV Past medical history of immediate or delayed hypersensitivity to compounds chemically similar to eltrombopag or their excipients. Treatment with another investigational product within 30 days. Prior treatment with eltrombopag, romiplostim, or any other TPO (thrombopoietin) receptor agonist. Positive result for HIV (Human Immunodeficiency Virus) antibody test. Pregnant or nursing (lactating) woman. Woman of child-bearing potential. Other protocol-defined inclusion/exclusion criteria may apply.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210000

Country

China

Facility Name

Novartis Investigative Site

City

Nanchang

State/Province

Jiangxi

ZIP/Postal Code

330006

Country

China

Facility Name

Novartis Investigative Site

City

Chengdu

State/Province

Sichuan

ZIP/Postal Code

610041

Country

China

Facility Name

Novartis Investigative Site

City

Tianjin

State/Province

Tianjin

ZIP/Postal Code

300020

Country

China

Facility Name

Novartis Investigative Site

City

Tianjin

ZIP/Postal Code

300052

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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 expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com

IPD Sharing URL

https://www.clinicalstudydatarequest.com

Learn more about this trial

Study to Assess the Safety and Efficacy of Eltrombopag in Chinese Refractory or Relapsed Severe Aplastic Anemia (SAA) Subjects.

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