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

Official title

A Randomized, Controlled, Multicenter, Double-blind Phase III Study Evaluating the Efficacy and Safety of Romiplostim N01 Combined With Standard Immunosuppressive Therapy (IST) Versus Placebo Combined With IST in Treatment-naïve Subjects With Severe Aplastic Anemia

Overview

This is a randomized, double-blind, multicenter trial designed to evaluate treatment with romiplostim N01+ IST compared with placebo + IST in the participants with treatment-naïve severe aplastic anemia.

Interventions

• Drug Romiplostim N01
  Starting from Day 1 of Week 1, administer the initial dose of romiplostim N01: 10 μg/kg. Platelet count (PLT) must be monitored weekly. The dose should be adjusted based on platelet values (adjusted by 5 μg/kg per change, see the table below for specific rules), administered once weekly, with a maximum dose of 20 μg/kg.
• Drug Cyclosporine A (CsA)
  Initiate at a dose of 5 mg/kg/day, administered orally in two divided doses (recommended at 12-hour intervals). The dose may be adjusted between 3 and 5 mg/kg/day based on the subject's tolerance.
• Drug pALG/ rATG
  25 mg/kg/day on Days 1 through 5 of Week 1.
• Drug Placebo
  Starting from Day 1 of Week 1, administer the initial dose of placebo: 10 μg/kg. Platelet count (PLT) must be monitored weekly. The dose should be adjusted based on platelet values (adjusted by 5 μg/kg per change, see the table below for specific rules), administered once weekly, with a maximum dose of 20 μg/kg.
• Drug Cyclosporine A (CsA)
  Initiate at a dose of 5 mg/kg/day, administered orally in two divided doses (recommended at 12-hour intervals). The dose may be adjusted between 3 and 5 mg/kg/day based on the subject's tolerance.
• Drug pALG/ rATG
  25 mg/kg/day on Days 1 through 5 of Week 1.

Primary outcome measures

• Complete Response (CR) rate at the 6-month time point of treatment. [Time frame: During 6 months of therapy]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07345000 · QL0911-304

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗