Background

Aplastic anemia (AA) is a bone marrow failure syndrome characterized by pancytopenia and hypocellular marrow, and is classified into severe (SAA) and non-severe (NSAA) subtypes. Thrombopoietin receptor agonists (TPO-RAs) have been shown to enhance the efficacy of immunosuppressive therapy (IST), particularly in SAA. Eltrombopag is widely used as a first-line agent in combination with IST(Townsley, Scheinberg et al. 2017), though concerns remain regarding its potential risk of clonal evolution. Romiplostim, a second-generation TPO-RA, has demonstrated durable platelet responses and trilineage hematopoietic improvement in both treatment-naïve and refractory AA(Jang, Tomiyama et al. 2021). Higher initial dosing, such as 10 µg/kg, may enhance hematopoietic stem and progenitor cell (HSPC) stimulation and accelerate platelet response (Lee, Lee et al. 2019, Zhao, Sicre De Fontbrune et al. 2019). Romiplostim N01, the first domestically developed biosimilar in China, received regulatory approval from the National Medical Products Administration (NMPA) in April 2024. However, clinical data on romiplostim in NSAA remain limited, and no studies to date have evaluated the efficacy and safety of Romiplostim N01 in this population.Study Design and Methods

We initiated a prospective, open-label, multi-centre, single-arm phase II trial (ChiCTR2500096280), conducted across multiple regions in China, to evaluate the efficacy and safety of Romiplostim N01 combined with cyclosporine or tacrolimus in patients diagnosed with NSAA and severe thrombocytopenia (platelet counts <30×10⁹/L). Romiplostim N01 is administered subcutaneously at a fixed initial dose of 10 µg/kg weekly during weeks 1–4, with subsequent dose adjustment (5–10 µg/kg/week) based on platelet response and toxicity from weeks 5–24. IST is administered continuously for ≥6 cycles. Platelet count exceeding 100×10⁹/L triggers a one-level dose reduction; Romiplostim No1 is withheld if counts exceed 200×10⁹/L.

Major eligibility criteria are: age ≥ 16, confirmed NSAA diagnosis, ECOG performance status of 0–2, QT interval <460 ms on electrocardiogram, adequate hepatic and renal function, prior TPO-RA recipients (including eltrombopag, hetrombopag, or avatrombopag) must complete a 1-month washout period before enrollment.Endpoints

The primary endpoint is the overall hematologic response rate at weeks 12 and 24. Secondary endpoints include the proportion of patients achieving any hematologic response (white blood cells, neutrophils, hemoglobin, or platelets) at weeks 4 and 25; cytogenetic changes; transfusion dependency; progression-free survival (PFS); safety; and health-related quality of life (HRQoL) assessed at week 25. Safety will be assessed by reporting the frequency of adverse events according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) criteria, and HRQoL will be measured using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).The study open to recruitment date is June 2024. A total of 40 subjects are anticipated.

The study open to recruitment date is June 2024. A total of 40 subjects are anticipated.Outlook

This trial aims to evaluate the efficacy and safety of Romiplostim N01 in combination with IST in patients diagnosed with NSAA, with the goal of improving hematologic response rates, reducing treatment failure, and enhancing quality of life. The findings are expected to support Romiplostim N01 as a novel and effective therapeutic option for NSAA.

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2025
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