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

Official title

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

Overview

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

This study is a prospective, open-label, randomized controlled, multicenter investigation conducted among adult patients with ND-CKD anemia in China, with the aim of exploring the rational hemoglobin target value for the treatment of patients with ND-CKD anemia using enarodustat.

This study plans to enrol 1,670 patients with non-dialysis chronic kidney disease (ND-CKD) anemia. After screening, patients who meet the inclusion criteria and do not meet the exclusion criteria will be randomly assigned at a 1:1 ratio to: the low Hb target value group: with a Hb target value of 11 g/dL; the high Hb target value group: with a Hb target value of 13 g/dL. The initial dose of enarodustat tablets in both groups is 4 mg once daily. The dose will be adjusted in accordance with the instructions and the requirements of different Hb value groups.

The follow-up period will last for 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.

Interventions

• Drug Enarodustat
  Patients are administered with enarodustat with dosage adjusted according to hemoglobin levels to achieve and maintain hemoglobin target over 96 weeks.

Primary outcome measures

• Improvement of quality of life [Time frame: At week 24]
• Effect on MACE+ events [Time frame: During 96 weeks]

Secondary outcome measures (6)

• Effect on blood transfusions [Time frame: During 96 weeks]
• Effect on thromboembolic events [Time frame: During 96 weeks]
• Effect on MACE events [Time frame: During 96 weeks]
• Effect on cardiovascular death [Time frame: During 96 weeks]
• Effect on renal events [Time frame: During 96 weeks]
• Effect on eGFR [Time frame: At weeks 24, 48, 72, and 96]

Eligibility criteria

Inclusion criteria

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

• 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;
• 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;
• 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;
• History of autoimmune diseases which could result in anemia such as systemic lupus erythematosus and ANCA vasculitis;
• History of active bleeding within 4 weeks prior to screening;
• 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;
• Severe heart failure (NYHA class IV) at screening;
• History of blood transfusion within 2 months prior to screening;
• History of usage of immunosuppressants or other immune therapies within 6 months prior to screening;
• Patients who are estimated to require dialysis, kidney transplantation, or major surgery within 6 months;
• 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;
• Receiving ESA combined with roxadustat treatment at screening;
• History of proliferative retinopathy or diabetic retinopathy requiring ophthalmological treatment;
• Severe hyperparathyroidism (iPTH ≥ 500 pg/mL);
• Severe active infections (such as active tuberculosis, fungal infections, etc.);
• Patients who are bedridden or have difficulty walking, or have a history of atrial fibrillation or deep vein thrombosis of the lower limbs;
• History of active tumors;
• Female patients who are pregnant or breastfeeding, or non-childbearing women who do not agree to effective contraception;
• 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;
• Patients who are currently participating in any other interventional clinical trial;
• Other reasons determined by the investigator not suitable for participation in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhongshan hospital, Fudan University — Shanghai

Identifiers

NCT: NCT06725810 · B2024-443

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗