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

Aplastic Anemia Clinical Trial

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

Status Completed

Clinical Trial 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).

Clinical Trial Description

This is a bridging study to support China registration. An estimation strategy rather than a formal hypothesis testing was pursued. Twenty subjects were enrolled into the study.

Treatment with eltrombopag started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count, up to 150 mg/day. Hematological response rate was assessed at 3, 6 months and 1 year (Week 13, 26 and 52) after starting the study treatment. Subjects in whom the treatment was found to be effective at 6 months continued to receive the treatment. Eltrombopag was discontinued if the treatment was ineffective at 6 months. Subjects were to discontinue eltrombopag before 6 months if any of the treatment discontinuation criteria were met.

Analysis set for the primary endpoint is Full Analysis Set (FAS) and subjects who discontinue from the study before Week 26 were treated as non-responders in the response analysis. Eltrombopag treatment was provided to subjects who were considered to require continued treatment at Week 26. After Week 26, if all of the hematologic response criteria (i.e., platelet count > 50×109/L, hemoglobin level > 100 g/L without transfusion, and neutrophil count > 1.0×109/L) remained fulfilled for more than 8 weeks, the dose of eltrombopag was decreased by half. If the response continued for further 8 weeks even at the decreased dose, the treatment was discontinued. If a decrease in any of the hematologic values (i.e., platelet count < 30×109/L, hemoglobin < 90 g/L, or neutrophil count < 0.5×109/L) was found after dose reduction, the dose was increased to the previous level. Furthermore, after treatment interruption, the treatment was restarted if any of the hematologic values decreased to the above-mentioned levels. The response assessment and safety evaluation were performed at Week 52.

The Extension part of this study started 1 year (Week 52) after the initiation of study treatment. This part was included in the study with an ethical consideration for subjects who required continued treatment. The continued treatment was provided up to the launch of eltrombopag after approval. Follow-up visit was performed 30 days after the discontinuation of eltrombopag treatment.

To better understand the PK characteristics of eltrombopag in Chinese SAA patient population, intensive PK blood samples was collected only in the initial 12 Chinese subjects receiving 25 mg/day dose after reaching steady-state to provide evaluable full PK profiles. Steady-state trough concentrations were collected at other dose levels and in other subjects. ;

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia

• NCT number: NCT03988608
• Study type: Interventional
• Source: Novartis
• Status: Completed
• Phase: Phase 2
• Start date: December 9, 2019
• Completion date: May 17, 2023