Enarodustat+CsA vs CsA in the Treatment of Newly-diagnosed TD-NSAA

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Not yet enrolling; Phase 3

Conditions: Transfusion-dependent Non-severe Aplastic Anemia

Treatments: Drug: Enarodustat; Drug: Cyclosporin (CSA)

Study type: Interventional

Funder types: Other

Identifiers

NCT07522996

ENA01

Details and patient eligibility

About

This study aimed to compare the efficacy and safety of enarodustat combined with cyclosporine versus cyclosporine alone in the treatment of TD-NSAA.

Full description

For TD-NSAA patients without HLA-matched donors, the firstline therapy is immunosuppressive therapy (IST) combined with thrombopoietin receptor agonists (TPO-RAs). However, some patients only have partial hematological responses, and their hemoglobin levels cannot be effectively increased.

Inflammatory factors such as IFN-γ, TNF-α, and IL-6 are significantly elevated in the bone marrow and peripheral blood of AA patients. Even in patients who respond effectively to IST, the proportion of CD3+ IFN+ and CD3+ TNF+ lymphocytes is still higher than that in healthy controls, and these cytokines may be involved in inhibiting the recovery of hemoglobin in patients.

HIF-PHI prevent the hydroxylation of HIF-α, thereby enabling the transcription and expression of genes related to erythropoiesis, such as those related to erythropoietin and iron transport. Roxadustat and enarodustat have been approved for the treatment of anemia in chronic kidney disease. Studies have shown that roxadustat can significantly reduce the levels of inflammatory factors such as IFN-γ, TNF-α, and IL-6 in the serum of patients with chronic kidney disease. A preliminary study has shown that roxadustat monotherapy in patients with insufficient erythroid response after IST can achieve a red blood cell response rate of 71.4%. Enarodustat has a similar mechanism to roxadustat, and in a rat model of inflammatory anemia, it was found that enarodustat can stimulate erythropoiesis by increasing iron utilization and improving inflammatory anemia. However, there are currently no studies on the use of enarodustat in AA patients.

Thus, this study aims to conduct a single-center, prospective, randomized controlled trial to compare the efficacy and safety of CsA+enarodustat with CsA monotherapy in newly diagnosed TD-NSAA patients.

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years old;
2. Diagnosed with aplastic anemia (AA) through routine blood tests, bone marrow puncture, bone marrow biopsy, and exclusion tests, and determined as transfusion-dependent non-severe aplastic anemia (TD-NSAA) according to the Camitta criteria; Hemoglobin<90g/L;
3. Had no HLA-matched donors or was not suitable for first-line allogeneic hematopoietic stem cell transplantation (HSCT);
4. With baseline liver and kidney functions <2 ULN;
5. ECOG score ≤ 2;
6. Signed the informed consent;

Exclusion criteria

1. Had other primary or secondary bone marrow failure (BMF) diseases, such as Fanconi anemia, congenital keratinization disorder, etc.;
2. With evidence of clonal hematological bone marrow diseases (MDS, AML) in cytogenetics;
3. PNH clone ≥ 50%;
4. Received HSCT before enrollment;
5. Previously used immunosuppressive treatments such as ATG, CsA, TPO receptor agonists (TPO-RAs), roxadustat;
6. Allergic or intolerant to enarodustat or CsA;
7. Pregnant or lactating patients;
8. Severe bleeding or infection that cannot be controlled by standard treatment;
9. Complicated with malignant tumors;
10. Participated in other clinical trials within 3 months;
11. Patients considered not suitable to participate in this study by the investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

CsA+Enarodustat

Experimental group

Description:

CsA 3-5mg/kg/d，trough concentration 100-200ng/ml Enarodustat 8mg qd

Treatment:

Drug: Cyclosporin (CSA)

Drug: Enarodustat

CsA monotherapy

Active Comparator group

Description:

CsA 3-5mg/kg/d，trough concentration 100-200ng/ml

Treatment:

Drug: Cyclosporin (CSA)