Romiplostim in Combination With CsA vs. CsA in the Treatment of Newly Diagnosed NSAA

Study Overview
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Brief Summary
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Aplastic anemia (AA) is a group of clinical syndromes caused by a significant decrease in bone marrow hematopoietic tissue from different etiologies, resulting in hematopoietic failure. Treatment options for patients with aplastic anemia are very limited. In a phase II/III, multicenter, open-label study exploring the efficacy and safety of romiplostim, the primary endpoint showed an overall response rate of 84% [95% CI 66-95%] at week 27. However, there are no prospective clinical data exploring whether romiplostim combined with ciclosporin (CsA) can further improve efficacy than ciclosporin monotherapy in newly diagnosed NSAA. Therefore, we aimed to compare the efficacy and safety of romiplostim in combination with CsA versus CsA monotherapy.

Detailed Description
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Aplastic anemia (AA) is a group of clinical syndromes caused by a significant decrease in bone marrow hematopoietic tissue from different etiologies, resulting in hematopoietic failure. Treatment options for patients with aplastic anemia are very limited. By binding to the thrombopoietin (TPO) receptor, thrombopoietin receptor agonists (TPO-RAs) can cause conformational changes in the TPO receptor, activate the JAK2/STATS pathway, and increase megakaryocyte progenitor cells proliferation and platelet production. At present, TPO-RAs including eltrombopag, lusutrombopag, romiplostim, and avatrombopag have been approved by FDA. In a phase II/III, multicenter, open-label study exploring the efficacy and safety of romiplostim, 31 patients with refractory AA were enrolled. The primary endpoint for the proportion of patients who achieved any hematological (platelet, neutrophil, and red blood cell) response at week 27 was 84% [95% CI 66-95%]. At week 53, the three-line response rate was 39% (95% CI 22-58%). However, there are no prospective clinical data exploring whether romiplostim combined with ciclosporin (CsA) can further improve efficacy than ciclosporin monotherapy in newly diagnosed NSAA. Since romiplostim and CsA have good safety, if it is proved that the combination of the two drugs is superior to ciclosporin monotherapy, it can quickly improve blood patterns in NSAA, avoid the use of more expensive ATG, and provide some help to reduce the economic burden of AA patients.

Official Title
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Romiplostim in Combination With Ciclosporin Versus Ciclosporin in the Treatment of Newly Diagnosed Non-severe Aplastic Anemia

Conditions
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Non Severe Aplastic Anemia

Intervention / Treatment
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* Drug: Romiplostim
* Drug: Ciclosporin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old. Clearly diagnosed as untreated NSAA. At least one of the following conditions was met at the time of enrollment: hemoglobin <90 g/L. Platelet <30×109/L, neutrophils <1.0×109/L. Baseline liver and kidney function (ALT, AST, Cr) was less than 2 times the normal value. No active infection; Not pregnant or breastfeeding. Agree to sign the consent form. The Eastern Cancer Collaboration Group (ECOG) score was 0-2. Exclusion Criteria: Pancytopenia caused by other causes, such as myelodysplastic syndrome (MDS). There is cytogenetic evidence of clonal hematologic bone marrow diseases (MDS, AML). PNH clone ≥50%. Had received hematopoietic stem cell transplantation (HSCT) before enrollment. Immunosuppressive therapy such as ATG or cyclosporine use for more than 2 weeks. Infection or bleeding that is not controlled by standard treatment. Allergic to recombinant TPO or Hitrepopar. Active HIV, HCV, HBV infection or cirrhosis, or portal hypertension. Any concomitant malignancy or local basal cell carcinoma of the skin within 5 years. Previous history of thromboembolic events, heart attack or stroke (including antiphospholipid antibody syndrome), and current use of anticoagulants. Women who are pregnant or nursing (lactation). Have participated in other clinical trials within 3 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romiplostim+CsA<br>Romiplostim 10 µg/kg, subcutaneous injection, once a week, for at least 3 months. Patients with platelet count ≥50×109/L can stop using, and continue to use with platelet count < 50×109/L. Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction. | Drug: Romiplostim<br>* Romiplostim 10 µg/kg, subcutaneous injection, once a week.<br>Drug: Ciclosporin<br>* Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml.<br>|
| Experimental: CsA<br>Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction. | Drug: Ciclosporin<br>* Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate (ORR) | Proportion of patients who achieved complete response and partial response. | 3, 6 months | 
| complete response rate (CRR) | Proportion of patients who achieved complete response. | 3, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse event rate | All adverse events that occur or worsen during treatment, as well as those that occur later but are believed by the investigator to be related to the investigational drug, will be reported. | 3, 6 months |