A Study of Romiplostim N01 Plus IST vs. Placebo Plus IST for Treatment-Naive Severe Aplastic Anemia

Inclusion criteria

• Age ≥15 years, regardless of sex (subjects ≥18 years old will be enrolled first; enrollment of subjects aged 15-18 years will commence after sufficient PK/PD data are obtained).
• Diagnosis of SAA or VSAA according to the British Journal of Haematology (BJH) guidelines. The diagnostic criteria for SAA are as follows:

①Bone marrow cellularity <25% of normal; or between 25% and <50%, with residual hematopoietic cells comprising <30%.

②Peripheral blood counts must meet at least two of the following three criteria (based on the lowest values from tests within 28 days prior to the first dose):

• Absolute neutrophil count (ANC) <0.5×10⁹/L
• Platelet count (PLT) <20×10⁹/L
• Absolute reticulocyte count (RET) <60×10⁹/L The diagnostic criterion for VSAA is: meeting the SAA criteria + ANC <0.2×10⁹/L.
• Written informed consent

Exclusion criteria

• History and/or concomitant presence of other primary or secondary bone marrow failure (BMF) syndromes, such as:

①Primary: Fanconi anemia, dyskeratosis congenita, congenital amegakaryocytic thrombocytopenia or Shwachman-Diamond syndrome, symptomatic paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndromes (MDS), clonal cytopenia of undetermined significance (CCUS), antibody-mediated BMF, idiopathic cytopenia of undetermined significance (ICUS), etc.

• Secondary: large granular lymphocyte (LGL) leukemia, infiltration of the bone marrow by other systemic malignancies, myelofibrosis, and acute hematopoietic arrest, etc.

Note: Asymptomatic PNH and hepatitis-associated SAA may be included if they meet all other inclusion criteria.

• Evidence of clonal cytogenetic abnormalities at screening.
• Participation in another clinical trial with investigational drugs or medical devices within 30 days prior to the first dose or within 5 half-lives of the investigational product (whichever is longer).
• Previous use of any of the following agents prior to the first dose:

• ATG/ALG

• Alemtuzumab

• Mycophenolate mofetil ④Sirolimus

• Tacrolimus ⑥High-dose cyclophosphamide (≥45 mg/kg/day)
• Cumulative cyclosporine A (CsA) therapy exceeding 4 weeks prior to the first dose. If cumulative use is ≤4 weeks, a washout period of >14 days prior to the first dose is required.
• Cumulative use of thrombopoietin receptor agonists (TPO-RAs) for >14 days prior to the first dose, or cumulative use ≤14 days with a washout period of <14 days, including:

• Romiplostim / Nplate® (romiplostim)

• Eltrombopag ③Hetrombopag ④Recombinant human thrombopoietin, etc.
• Previous history of hematopoietic stem cell transplantation.
• Uncontrolled bleeding and/or infection after standard treatment prior to the first dose [defined as persistent signs/symptoms related to infection without improvement despite appropriate antibiotic and/or other therapy], or requiring intravenous (IV) antibiotic administration.
• Concomitant active CMV and EBV infection (positive test).