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

Enarodustat Plus CsA Versus CsA Monotherapy in the Treatment of Newly-diagnosedTD-NSAA: a Single-center Randomized Trial

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

Study Overview

• Status: Withdrawn
• Conditions: Transfusion-dependent Non-severe Aplastic Anemia
• Intervention / Treatment: Drug: Enarodustat; Drug: Cyclosporin (CSA)

Detailed 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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CsA+Enarodustat; CsA 3-5mg/kg/d，trough concentration 100-200ng/ml Enarodustat 8mg qd	Drug: Enarodustat; Enarodustat 8mg qd; Drug: Cyclosporin (CSA); CsA 3-5mg/kg/d
Active Comparator: CsA monotherapy; CsA 3-5mg/kg/d，trough concentration 100-200ng/ml	Drug: Cyclosporin (CSA); CsA 3-5mg/kg/d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	overall response rate (ORR) = complete response rate (CRR) + partial response rate (PRR)	6-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	ORR = CRR + PRR	3-month, 12-month
RBC-TI rate	Proportion of patients who achieve red blood cell transfusion independence for 8 weeks or longer	3-month, 6-month, 12-month
hemoglobin response rate	Proportion of patients with hemoglobin response	3-month, 6-month, 12-month
AE rate	According to CTCAE, the proportion of patients with adverse events (AEs)	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: April 4, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Peptides; Amino Acids, Peptides, and Proteins; Polycyclic Compounds; Macrocyclic Compounds; Peptides, Cyclic; Cyclosporins; Cyclosporine; enarodustat
• Other Study ID Numbers: ENA01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No