Treatment-naïve Severe Aplastic Anemia
Conditions
Brief summary
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
DRUGRomiplostim 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.
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.
DRUGpALG/ rATG
25 mg/kg/day on Days 1 through 5 of Week 1.
DRUGPlacebo
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.
Sponsors
Qilu Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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). 2. 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): 1. Absolute neutrophil count (ANC) \<0.5×10⁹/L 2. Platelet count (PLT) \<20×10⁹/L 3. Absolute reticulocyte count (RET) \<60×10⁹/L The diagnostic criterion for VSAA is: meeting the SAA criteria + ANC \<0.2×10⁹/L. 3. Written informed consent
Exclusion criteria
1. 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. 2. Evidence of clonal cytogenetic abnormalities at screening. 3. 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). 4. 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) 5. 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. 6. 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. 7. Previous history of hematopoietic stem cell transplantation. 8. 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. 9. Concomitant active CMV and EBV infection (positive test).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) rate at the 6-month time point of treatment. | During 6 months of therapy | Proportion of subjects achieving hematopoietic complete response at the 6-month. Hematopoietic complete response is defined as: hemoglobin ≥10 g/dL, absolute neutrophil count ≥1×10⁹/L, and platelet count ≥100×10⁹/L. |
Contacts
Primary Contactjun shi, Professor
Outcome results
None listed