Clinical trial NCT06725810: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Chronic Kidney Disease Associated Anemia
Keywords: HIF-PH inhibitor
anemia
chronic kidney disease
quality of Life
major adverse cardiovascular events
enarodustat
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
Collaborators: name: Shenzhen Salubris Pharmaceuticals Co., Ltd. (Salubris)
First posted: 2024-12-10
Enrollment: 1670
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Improvement of quality of life
timeFrame: At week 24
measure: Effect on MACE+ events
timeFrame: During 96 weeks
Secondary outcomes:
measure: Effect on blood transfusions
timeFrame: During 96 weeks
measure: Effect on thromboembolic events
timeFrame: During 96 weeks
measure: Effect on MACE events
timeFrame: During 96 weeks
measure: Effect on cardiovascular death
timeFrame: During 96 weeks
measure: Effect on renal events
timeFrame: During 96 weeks
measure: Effect on eGFR
timeFrame: At weeks 24, 48, 72, and 96
Other outcomes:
measure: Effect on the usage of iron agents
timeFrame: During 96 weeks
measure: Effect on the indices of iron metabolism
timeFrame: at weeks 12, 24, 48, 72, and 96
measure: Difference of dosage of enarodostat
timeFrame: During 24 weeks
measure: Evaluation of adverse drug events
timeFrame: during 96 weeks
Locations:
city: Shanghai
country: China
facility: Zhongshan hospital, Fudan University
state: Shanghai
Study officials:
References: