Using enarodustat to correct anemia in adults with non-dialysis chronic kidney disease

A Prospective, Open-label, Randomized, Multicenter Study on the Rational Hemoglobin Target Value in Patients With Anemia of Non-dialysis Chronic Kidney Disease Treated With Enarodustat

This test gives enarodustat to adults with non-dialysis chronic kidney disease and anemia to see if aiming for a higher hemoglobin (13 g/dL) versus a lower hemoglobin (11 g/dL) improves quality of life and is safe.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 1670 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Zhongshan Hospital (Academic / other)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06725810 on ClinicalTrials.gov

What this trial studies

This is a prospective, open-label, randomized multicenter trial in China that will enroll about 1,670 adults with non-dialysis chronic kidney disease (stages 2–5) and anemia. Participants are randomized 1:1 to an enarodustat dosing strategy targeting either hemoglobin 13 g/dL or hemoglobin 11 g/dL, with dose adjustments to maintain the assigned target over 96 weeks. The main clinical outcome is change in the 36-Item Short Form Health Survey (SF-36) at week 24, and the key safety outcome is time to major adverse cardiovascular events (MACE+) over 96 weeks. The initial enarodustat dose is 4 mg once daily for all patients, with subsequent titration per protocol and hemoglobin target group.

Who should consider this trial

Good fit: Adults aged 18–75 with non-dialysis chronic kidney disease (eGFR ~10–90 mL/min/1.73m2), anemia meeting the trial hemoglobin criteria, adequate iron stores (ferritin >100 µg/L or TSAT >20%), and body weight 45–100 kg who can consent and attend study visits are ideal candidates.

Not a fit: People on dialysis, those with uncontrolled hypertension or very heavy proteinuria, severe comorbid conditions, or inadequate iron stores are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the trial could identify an optimal hemoglobin target when treating ND-CKD anemia with enarodustat that improves quality of life without excess cardiovascular risk.

How similar studies have performed: Other drugs in the HIF-PH inhibitor class (for example roxadustat and daprodustat) have effectively raised hemoglobin in CKD-related anemia, but cardiovascular safety and optimal hemoglobin targets remain under study.

Eligibility criteria

Inclusion Criteria:

1. Aged 18-75 years at the time of consent to participate;
2. Body weight ranged from 45 to 100 kg;
3. Diagnosed with CKD stages 2-5 (10 ≤ eGFR \< 90 mL/min/1.73m2) and were not dialysis dependent;
4. Diagnosed with renal anemia:

1)Hemoglobin level of 6 - 10 g/dL for those who have not received ESA or HIF-PHI treatment within 6 weeks at screening; 2)Hemoglobin level of 8 - 12 g/dL for those who are currently receiving ESA (ESA dosage ≤ 10,000 IU/week) or HIF-PHI (roxadustat dosage≤ 100 mg TIW) at screening; 5. Serum ferritin \> 100 μg/L or transferrin saturation \> 20% at screening; 6. Voluntary participation in the trial and signing of the informed consent form.

Exclusion Criteria:

1. Uncontrolled hypertension identified as systolic blood pressure \>160mmHg or diastolic blood pressure \>100mmHg after 4 weeks of regular and adequate drug therapy prior to screening;
2. Uncontrolled proteinuria identified as UACR \>3000mg/g or 24-hour urine protein \>3.5g in non-diabetic patients and UACR of \>5000mg/g or 24-hour urine protein \>5.5g in diabetic patients;
3. Anemia due to other reasons except CKD including systemic hematological disorders (such as myelodysplastic syndrome, aplastic anemia, etc.), hemolytic anemia, hemorrhagic anemia or cancer-related anemia;
4. History of autoimmune diseases which could result in anemia such as systemic lupus erythematosus and ANCA vasculitis;
5. History of active bleeding within 4 weeks prior to screening;
6. History of serious thrombotic event such as a myocardial infarction, cerebral infarction, pulmonary embolism, unstable angina, or PCI or cardiac surgery within 6 months prior to screening;
7. Severe heart failure (NYHA class IV) at screening;
8. History of blood transfusion within 2 months prior to screening;
9. History of usage of immunosuppressants or other immune therapies within 6 months prior to screening;
10. Patients who are estimated to require dialysis, kidney transplantation, or major surgery within 6 months;
11. Severe liver and biliary system complications (AST or ALT \>3 times the upper limit of normal, total bilirubin \>2 times the upper limit of normal) at screening;
12. Receiving ESA combined with roxadustat treatment at screening;
13. History of proliferative retinopathy or diabetic retinopathy requiring ophthalmological treatment;
14. Severe hyperparathyroidism (iPTH ≥ 500 pg/mL);
15. Severe active infections (such as active tuberculosis, fungal infections, etc.);
16. Patients who are bedridden or have difficulty walking, or have a history of atrial fibrillation or deep vein thrombosis of the lower limbs;
17. History of active tumors;
18. Female patients who are pregnant or breastfeeding, or non-childbearing women who do not agree to effective contraception;
19. Patients with a history of severe drug allergies (such as anaphylactic shock), or known allergies to any of the active ingredients or excipients of enarodostat;
20. Patients who are currently participating in any other interventional clinical trial;
21. Other reasons determined by the investigator not suitable for participation in the study.

Where this trial is running

Shanghai, Shanghai Municipality

• Zhongshan hospital, Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Xiaoqiang Ding — Fudan University
• Study coordinator: Xiaoqiang Ding

Conditions Chronic Kidney Disease Associated Anemia; HIF-PH inhibitor; anemia; chronic kidney disease; quality of Life; major adverse cardiovascular events; enarodustat