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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (6)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Zhongshan hospital, Fudan University — Шанхай

Идентификаторы

NCT: NCT06725810 · B2024-443

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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