Correction of Anemia with Enarodustat in Non-dialysis Dependent Chronic Kidney Disease

Phase 4

Not yet recruiting

• Conditions: Chronic Kidney Disease Associated Anemia
• Interventions: Drug: enadustat

• Registration Number: NCT06725810
• Lead Sponsor: Shanghai Zhongshan Hospital

Brief Summary

The CANNON trial is a prospective, open-label, randomized, multicenter study designed to investigate rational hemoglobin target value in patients with anemia of non-dialysis chronic kidney disease treated with enarodustat. Eligible patients are randomly assigned 1:1 to the high-hemoglobin target group （hemoglobin of 13 g/dl）and low-hemoglobin target group （hemoglobin of 11 g/dl）and administered with enarodustat to achieve and maintain target hemoglobin over 96 weeks. The first primary endpoint was the difference of mean change in 36-Item Short Form Health Survey at week 24. The second primary endpoint was safety endpoints included time to major adverse cardiovascular + event (MACE+; all-cause mortality, myocardial infarction, stroke, and congestive heart failure requiring hospitalization) during 96 weeks.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-12
• Study Start: 2024-12-01
• Study First Submitted: 2024-12-05
• Study First Submitted QC: 2024-12-05
• Last Update Submitted: 2024-12-05
• Study First Posted: 2024-12-10
• Last Update Posted: 2024-12-10
• Primary Completion: 2029-01-01
• Study Completion: 2029-02-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1670

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
high-hemoglobin target group	enadustat	Patients are managed to achieve and maintain hemoglobin target of 13 g/dl over 96 weeks.
low-hemoglobin target group	enadustat	Patients are managed to achieve and maintain hemoglobin target of 11 g/dl over 96 weeks.

Primary Outcome Measures

Name	Time	Method
Improvement of quality of life	At week 24	Mean change in 36-Item Short Form Health Survey
Effect on MACE+ events	During 96 weeks	First occurence of major adverse cardiovascular + event (MACE+; all-cause mortality, myocardial infarction, stroke, and congestive heart failure requiring hospitalization) .

Secondary Outcome Measures

Name	Time	Method
Effect on blood transfusions	During 96 weeks	Difference in the proportion of patients receiving blood transfusions between high- and low-hemoglobin target groups
Effect on thromboembolic events	During 96 weeks	The variance in the risk of thromboembolic events (excluding those in the cardiovascular system of the heart and brain) between high- and low-hemoglobin target groups
Effect on MACE events	During 96 weeks	Dissimilarity in the risk of the first occurrence of MACE events between high- and low-hemoglobin target groups
Effect on cardiovascular death	During 96 weeks	Discrepancy in the risk of cardiovascular death between high- and low-hemoglobin target groups
Effect on renal events	During 96 weeks	Divergence in the incidence of renal events (defined as a reduction in eGFR by more than 50%, persistent dialysis for more than 3 months, or kidney transplantation) between high- and low-hemoglobin target groups
Effect on eGFR	At weeks 24, 48, 72, and 96	Difference in the mean change of eGFR from baseline between high- and low-hemoglobin target groups

Trial Locations

Locations (1)

Zhongshan hospital, Fudan University; 🇨🇳 Shanghai, Shanghai, China