NCT07523009

CsA+EPAG/HPAG+Romiplostim N01 in the Treatment of Newly-diagnosed SAA/TD-NSAA

Cyclosporine, Eltrombopag or Hetrombopag, and Romiplostim N01 in the Treatment of Newly-diagnosed Transfusion-dependent Non-severe Aplastic Anemia/ Severe Aplastic Anemia

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (estimated)
• Sponsor: Peking Union Medical College Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study aimed to explore the efficacy and safety of cyclosporine (CsA) combined with eltrombopag (EPAG)/hetrombopag (HPAG) and romiplostim N01 in the treatment of newly-diagnosed transfusion-dependent aplastic anemia (TD-NSAA) and severe aplastic anemia (SAA)

Detailed description

For SAA/TD-NSAA patients without HLA-matched donors and those over 40 years old, the first choice is immunosuppressive therapy (IST) + cyclosporine A (CsA) combined with thrombopoietin receptor agonists (TPO-RAs). TPO-RAs could bind to the thrombopoietin (TPO) receptor, causing conformational changes in the TPO receptor and activating the JAK2/STAT5 pathway, thereby increasing the proliferation of megakaryocyte progenitor cells and platelet production. Previous studies have shown that compared with IST alone, the combination of IST and eltrombopag (EPAG)/hetrombopag (HPAG) as the first-line treatment for SAA can increase the overall response rate (ORR) to 60%-70%. However, ATG treatment requires hospitalization and has significant toxic effects, leading to a high risk of complications in the elderly or patients with poor health. Therefore, in recent years, treatment regimens without ATG have also been gradually explored. The results of the SOAR trial showed that in newly diagnosed SAA patients, the overall hematological response rate after 6 months of CsA + EPAG was 46%. In a phase II/III study for refractory AA, romiplostim monotherapy achieved an ORR of 84% at week 27. Although both romiplostim and eltrombopag/hyrtiopeg activate the TPO receptor (c-Mpl), there are differences and complementarities in their molecular mechanisms. Romiplostim is a peptide mimetic that binds to the extracellular domain of the receptor to mimic endogenous TPO; while eltrombopag and hetrombopag are small molecules that target the transmembrane domain, among which hetrombopag replaces the biphenyl structure to enhance lipophilicity, improve efficacy, and reduce liver toxicity. The binding sites of the two drugs are spatially separated and may produce a synergistic effect through different intensities and dynamics of downstream STAT, PI3K/AKT, and other signaling pathways.

Conditions

• Severe Aplastic Anemia (SAA)
• Transfusion-dependent Non-severe Aplastic Anemia

Interventions

Type	Name	Description
DRUG	Cyclosporine (CsA)	CsA 3-5mg/kg/d
DRUG	Thrombopoietin Receptor Agonist	Eltrombopag: initial dose 50mg/d, maximum dose 150mg/d hetrombopag 7.5mg/d, maximum dose 15mg/d
DRUG	Romiplostim N01	Romiplostim N01: 20 µg/kg, subcutaneously, once a week

Timeline

• Start date: 2026-04-01
• Primary completion: 2028-12-01
• Completion: 2029-12-01
• First posted: 2026-04-13
• Last updated: 2026-04-13