Phase 2
N=21
A Study to Assess the Safety and Efficacy of Eltrombopag in Japanese Subjects With Refractory, Moderate or More Severe Aplastic Anemia
Cytopaenia
Bottom Line
View on ClinicalTrials.gov: NCT02148133 ↗Enrolled (actual)
21
Serious AEs
28.6%
Results posted
May 2019
Primary outcome: Primary: Hematological Response at Week 26 — 47.6 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Eltrombopag 12.5 mg (Drug); Eltrombopag 25 mg (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Sep 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Hematological Response at Week 26 |
47.6 | — |
| SECONDARY Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time |
12.19; 6.32; 13.09; 23.50; 21.50; 36.69 | — |
| SECONDARY Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time |
70.4; 4.9; 8.8; 19.3; 24.0; 32.8 | — |
| SECONDARY Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time |
0.8247; 0.3321; 0.2046; 0.4537; 0.5236; 0.8579 | — |
| SECONDARY Hematological Response at Week 13 in Terms of the Platelet Count, Hemoglobin Level and Neutrophil Count |
61.9 | — |
| SECONDARY Duration of Hematological Response in Participants Who Responded at the Week 13 |
10.68; 32.62; 19.19; 3.02 | — |
| SECONDARY Volume of (Platelet and RBC) Transfusion in Each Period |
600.0; 1663.2; 400.0; 1152.9; 280.0; 800.0 | — |
| SECONDARY Frequency of (Platelet and RBC) Transfusion in Each Period |
3.0; 4.1; 2.0; 2.9; 1.4; 1.9 | — |
| SECONDARY Percentage of Participants With Reduced Volume of Transfusion (Platelet and RBC) |
83.3; 73.7 | — |
| SECONDARY Percentage of Participants Who Become Transfusion (Platelet and RBC) Independent |
66.7; 47.4 | — |
| SECONDARY Long-term Safety and Tolerability of Eltrombopag |
100; 85.7; 81.0; 42.9; 4.8; 28.6 | — |
| SECONDARY Number of Participants With Bleeding Events and Severity of Bleeding |
11; 9; 2; 6; 5; 1 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) for Eltrombopag |
6410 | — |
| SECONDARY Time to Reach the Maximum Plasma Concentration (Tmax) for Eltrombopag |
2.00 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Subject Across All Treatments (AUC 0-t) and Over the Dosing Interval (AUC 0-tau) for Eltrombopag |
123000; 99200 | — |
| SECONDARY Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15 |
4530; 5240; 5980; 5870; 5720; 5430 | — |
Summary
This was a non-randomized, open-label, phase II study to assess the efficacy and safety of eltrombopag in Japanese moderate or more severe aplastic anemia (AA) subjects with a platelet count <30,000/microliter who were refractory to anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST), who have relapsed after ATG-based IST, or who are ineligible for ATG-based IST.
Eltrombopag was expected to improve trilineage blood cells and decrease transfusion frequency based on the result from the previous study in patients with severe AA. This study used the hematologic response rate, defined as the proportion of subjects showing improvement in at least one of the three blood cell lineages or a decrease in blood transfusion volume, as the primary endpoint.
A total of 36 subjects were screened and 21 were enrolled in the study. Treatment with eltrombopag started at 25 milligram (mg)/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day. Response assessment was performed at 3 months after starting the study treatment (Week 13). Subjects in whom the treatment was assessed as effective continued with the study treatment. Subjects in whom the treatment was assessed as effective (when meeting any of the response criteria) at 6 months after starting the study treatment (Week 26) might enter the extension phase and continue the treatment with eltrombopag. The primary endpoint was the hematologic response rate at Week26.
Eligibility Criteria
Key Inclusion Criteria
- Subject has given written informed consent. If a subject is under 20 years, both the subject and the subject's legally acceptable representative have to give informed consent.
- Japanese subjects aged >=18 and 40 milli international unit /milliliter (mIU/mL) or estradiol =50%
- Presence of chromosomal aberration (-7/7q- detected by fluorescence in situ hybridization (FISH), or other aberrations detected by Giemsa (G)-band staining) Note: Subjects with the result by G-band staining (bone marrow aspiration) not adopted into the abnormal clone definition of An International System for Human Cytogenetic Nomenclature (ISCN) can be enrolled as no chromosomal aberration.
- Past history of thromboembolism or current use of anticoagulants. Note: Subjects with antiphospholipid antibody syndrome (APS) should not be enrolled.
- Past or current history of malignant tumor. Note: Subjects who have a history of completely resected malignant tumor and have been disease-free for 5 years are eligible.
- Subjects who test positive for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at screening. Note: Subjects with inactive hepatitis B may be enrolled. Judgment of inactive hepatitis B will be done by the medical advisor.
- Subjects with concurrent uncontrollable severe infection (e.g., sepsis)
- Hepatic cirrhosis
- Cardiac disorder (congestive heart disease of New York Heart Association (NYHA) functional classification Grade II/III/IV), or arrhythmia with a risk of thrombosis (e.g., atrial fibrillation). Note: 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.
- Alcohol or drug abuse
- Pregnant women (a positive serum or urine pregnancy test within 7 days prior to the first dose of study treatment) or lactating women. Note: Female subjects who are lactating are eligible to participate if they discontinue nursing prior to the first dose of study treatment and refrain from nursing until 5 days after the treatment completion.
- Past history of immediate or delayed hypersensitivity to compounds chemically similar to eltrombopag or their activators
- Treatment with another investigational product within 30 days or the period 5-fold longer than the half-life of the investigational product, whichever longer, prior to the first dose of eltrombopag
- Prior treatment with eltrombopag, romiplostim, or any other Thrombopoietin (TPO) receptor agonist
- Use of prohibited concomitant medications.
Data sourced from ClinicalTrials.gov (NCT02148133). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.