Conditions: Aplastic Anemia
Keywords: Eltrombopag rabbit anti-thymocyte globulin additive effect cyclosporine A bone marrow hematopoietic stem cells pancytopenia leukopenia platelets throbocytopenia mature blood cells bone marrow biopsy
Enrollment: 10
Healthy volunteers: no

Brief 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.

Detailed description:

Arms:
arm 1: Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag wasadministered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26.After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.

Interventions: intervention 1: Eltrombopag intervention 2: Rabbit ATG intervention 3: CsA
Intervention descriptions: intervention 1: Eltrombopag was provided as white round film-coated tablets containing 12.5 mg or 25 mg of eltrombopag free acid (SB-497115-GR, eltrombopag). intervention 2: Rabbit ATG, as an intravenous drip infusion, diluted by 500 mL of saline or 5% glucose injection was administered at a dose of 2.5 to 3.75 mg per kg per day as a slow intravenous infusion over 6 hours. intervention 3: CsA as capsules, oral solution, or fine granule, was administered at a dose of 3 mg per kg twice a day.

Protocol document: