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

Qilu Pharmaceutical

Status and phase: Not yet enrolling; Phase 3

Conditions: Treatment-naïve Severe Aplastic Anemia

Treatments: Drug: Cyclosporine A (CsA); Drug: Romiplostim N01; Drug: pALG/ rATG; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07345000

QL0911-304

Details and patient eligibility

About

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.

Enrollment: 210 estimated patients

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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210 participants in 2 patient groups

Romiplostim N01+ IST

Experimental group

Treatment:

Drug: Cyclosporine A (CsA)

Drug: pALG/ rATG

Drug: pALG/ rATG

Drug: Romiplostim N01

Drug: Cyclosporine A (CsA)

Placebo+ IST

Active Comparator group

Treatment:

Drug: Placebo

Drug: Cyclosporine A (CsA)

Drug: pALG/ rATG

Drug: pALG/ rATG

Drug: Cyclosporine A (CsA)