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

Sponsors

Lead sponsor: Novartis Pharmaceuticals

Source Novartis
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).

Overall Status Recruiting
Start Date December 9, 2019
Completion Date April 28, 2023
Primary Completion Date August 31, 2021
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Hematologic response rate 6 months (Week 26)
Secondary Outcome
Measure Time Frame
Hematologic response rate Week 13 and Week 52
Changes in platelet count Baseline to Week 26 or up to 3.5 years
Changes in hemoglobin count Baseline to Week 26 or up to 3.5 years
Changes in neutrophil count Baseline to Week 26 or up to 3.5 years
Time to hematologic response Baseline to Week 26 or up to 3.5 years
Duration of hematologic response Baseline to Week 26 or up to 3.5 years
Frequency of transfusion Baseline to Week 26 or up to 3.5 years
Volume of transfusion Baseline to Week 26 or up to 3.5 years
Plasma concentration of eltrombopag including the trough concentrations Baseline to Week 26
Rate of clonal evolution Baseline to Week 26 or up to 3.5 years
Enrollment 20
Condition
Intervention

Intervention type: Drug

Intervention name: Eltrombopag 25 mg

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

Arm group label: Eltrombopag

Other name: ETB115

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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals
Overall Contact

Last name: Novartis Pharmaceuticals

Phone: +41613241111

Email: [email protected]

Location
facility status
Novartis Investigative Site | Chengdu, Sichuan, 610041, China Recruiting
Novartis Investigative Site | Tianjin, Tianjin, 300020, China Recruiting
Novartis Investigative Site | Beijing, 100730, China Recruiting
Location Countries

China

Verification Date

May 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Eltrombopag

Arm group type: Experimental

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

Patient Data Yes
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov