Phase 2
N=10
Eltrombopag in Combination With Rabbit Anti-thymocyte Globulin/Cyclosporine A in Naive Aplastic Anemia (AA) Subjects
Aplastic Anemia
Bottom Line
View on ClinicalTrials.gov: NCT02404025 ↗Enrolled (actual)
10
Serious AEs
20.0%
Results posted
Jul 2019
Primary outcome: Primary: ORR at 6 Months: Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at Week 26 — 7; 0; 7 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Eltrombopag (Drug); Rabbit ATG (Drug); CsA (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Jul 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY ORR at 6 Months: Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at Week 26 |
7; 0; 7 | — |
| SECONDARY ORR at 3 Months |
2 | — |
| SECONDARY Complete Response (CR), and Partial Response (PR) Rate at 3 Months |
0; 2 | — |
| SECONDARY CR Rate Based on the Criteria Used in NIH 12-H-0150 Study at 6 Months |
1 | — |
| SECONDARY Changes in Hematology Parameters (Haemoglobin) in the Absence of Platelet Transfusion |
24.6; 39.0 | — |
| SECONDARY Changes in Hematology Parameters in the Absence of Platelet Transfusion |
1.2196; 1.2978; 66.94; 107.33; 30.0175; 48.0900 | — |
| SECONDARY Frequency of Platelet and Red Blood Cells (RBC) Transfusions |
4.0; 1.0; 3.4; 1.0 | — |
| SECONDARY Volume of Platelet and RBC Transfusions |
1600.0; 400.0; 687.5; 200.0 | — |
| SECONDARY The Proportion of Subjects Whose Transfusion Unit (or Volume) Are Decreased or Who Became Transfusion (Platelet, RBC) Independent |
6; 4; 8; 5 | — |
| SECONDARY Duration of Hospitalization |
49.0 | — |
| SECONDARY Time to Onset of CR and PR |
3.75 | — |
| SECONDARY Duration of CR or PR |
17.28 | — |
| SECONDARY Degree of Exposure to Eltrombopag : Average Daily Dose |
43.8 | — |
| SECONDARY Degree of Exposure to Eltrombopag : Cumulative Dose |
17687.5 | — |
| SECONDARY Degree of Exposure to Eltrombopag : Days on Study |
493.7 | — |
| SECONDARY Number of Participants With Adverse Events |
10; 8; 5; 8; 2 | — |
| SECONDARY Vital Signs (Blood Pressure) as a Measure of Safety and Tolerability |
115.7; 126.4; 64.3; 76.9 | — |
| SECONDARY 12-lead Electrocardiogram (ECG) as Measure of Safety and Tolerability |
8; 2; 0; 6; 3; 0 | — |
| SECONDARY The Trough Concentrations of Eltrombopag Following Repeat Doses of at 75 mg, 50 mg and 25 mg |
6070; 20800; 21800 | — |
| SECONDARY The Concentration After 4 Hours of Dose of Eltrombopag 75 mg |
21800; 28400 | — |
| SECONDARY Composite of Laboratory Parameters Assessment as a Safety Measure (Haemoglobin and Albumin). |
77.2; 102.4; 38.7; 44.9 | — |
| SECONDARY Composite of Laboratory Parameters Assessment as a Safety Measure (Lymphocytes and Neutrophils). |
1.896; 2.682; 1.3943; 0.7108; 0.4033; 1.6120 | — |
| SECONDARY Composite of Laboratory Parameters Assessment as a Safety Measure (Alcaline Phosphatase and Aspartate Amino Transferase) . |
186.7; 319.6; 14.3; 16.8; 14.9; 18.8 | — |
| SECONDARY Composite of Laboratory Parameters Assessment as a Safety Measure. |
2.565; 2.850; 5.301; 6.080; 7.866; 8.930 | — |
| SECONDARY Vital Signs (Temperature) as a Measure of Safety and Tolerability |
36.55; 36.71 | — |
| SECONDARY Vital Signs (Pulse Rate) as a Measure of Safety and Tolerability |
76.2; 80.4 | — |
Summary
This was an open label, non-randomized, phase II study of eltrombopag in combination with rabbit ATG/CsA in subjects with moderate or more severe AA who did not received prior ATG/ALG-based immunosuppressive therapy. The objective was to assess additive effects of eltorombopag on overall response rate (ORR) at 6 months (Week 26) of treatment with ATG/CsA. Subjects were assessed at least weekly for safety during the period from the start of ATG/CsA to 4 weeks after the start of administration of eltrombopag. After that, subjects had visits every 2 weeks until Week 26. Subjects in whom the treatment was assessed as effective at Week 26 could continued treatment with eltrombopag after 6 months when clinically indicated at the discretion of the investigator. There were five follow-up visits: at discontinuation of the treatment of eltrombopag, and Weeks 1, 2, 3, 4 and 26 after treatment discontinuation. As this study was the first Japanese phase II study in which this product was administered in combination with ATG/CsA to subjects with naive moderate or more severe AA, the subject number of this study was determined to be 10 based on the feasibility survey.
Eligibility Criteria
Inclusion Criteria
- Japanese subjects aged >=18 and =71 and =2 units per month) is required: Reticulocyte 40 milli-international units (mIU)/milliliter (mL) or estradiol 50% by flow cytometric analysis.
- Pre-existing cardiac disease (congestive heart failure New York Heart Association (NYHA) Grade II/III/IV), or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation)
- Past history of thromboembolic event (including anti-phospholipid antibody syndrome) and current use of anticoagulants.
- Subjects with past or current malignancy. 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.
- Infection not adequately responding to appropriate therapy.
- Subject with liver cirrhosis
- Subjects with any clinically significant severe cardiac, renal, or hepatic medical condition.
- Pregnant women (a positive serum or urine pregnancy test within 7 days prior to the first dose of ATG/CsA or lactating women) Note: Female subjects who are lactating are eligible to participate if they discontinue nursing prior to the first dose of ATG/CsA and refrain from nursing until 5 days after the completion of treatment with eltrombopag.
- Known hypersensitivity, intolerance or allergy to rabbit ATG, cyclosporine A, eltrombopag or any of their excipients.
- Current alcohol or drug abuse.
- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) proceeding the first dose of ATG/CsA.
- Subjects who is not candidates for ATG.
- Subjects who is not candidates for CsA.
- History of treatment with eltrombopag, romiplostim or other thrombopoietin-receptor (TPO-R) agonists.
Data sourced from ClinicalTrials.gov (NCT02404025). 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.