Clinical trial NCT06009497: Romiplostim in Combination With CsA vs. CsA in the Treatment of Newly Diagnosed NSAA
Official title: Romiplostim in Combination With Ciclosporin Versus Ciclosporin in the Treatment of Newly Diagnosed Non-severe Aplastic Anemia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Non Severe Aplastic Anemia
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2023-08-24
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years old.
2. Clearly diagnosed as untreated NSAA.
3. 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.
4. Baseline liver and kidney function (ALT, AST, Cr) was less than 2 times the normal value.
5. No active infection; Not pregnant or breastfeeding.
6. Agree to sign the consent form.
7. The Eastern Cancer Collaboration Group (ECOG) score was 0-2.

Exclusion Criteria:

1. Pancytopenia caused by other causes, such as myelodysplastic syndrome (MDS).
2. There is cytogenetic evidence of clonal hematologic bone marrow diseases (MDS, AML).
3. PNH clone ≥50%.
4. Had received hematopoietic stem cell transplantation (HSCT) before enrollment.
5. Immunosuppressive therapy such as ATG or cyclosporine use for more than 2 weeks.
6. Infection or bleeding that is not controlled by standard treatment.
7. Allergic to recombinant TPO or Hitrepopar.
8. Active HIV, HCV, HBV infection or cirrhosis, or portal hypertension.
9. Any concomitant malignancy or local basal cell carcinoma of the skin within 5 years.
10. Previous history of thromboembolic events, heart attack or stroke (including antiphospholipid antibody syndrome), and current use of anticoagulants.
11. Women who are pregnant or nursing (lactation).
12. Have participated in other clinical trials within 3 months

Primary outcomes:
measure: overall response rate (ORR)
timeFrame: 3, 6 months
measure: complete response rate (CRR)
timeFrame: 3, 6 months
Secondary outcomes:
measure: adverse event rate
timeFrame: 3, 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking union medical college hospital
Study officials:
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