A Study to Evaluate Efficacy and Safety of JTZ-951 Compared to Darbepoetin Alfa in Korean Renal Anemia Patients Receiving Hemodialysis.

Study Overview
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Brief Summary
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JTZ-951 is a currently being developed as a treatment for renal anemia. This study aims to evaluate the efficacy and safety of JTZ-951 following a switch from erythropoiesis-stimulating agent (ESA) in Korean subjects receiving HemoDialysis with renal anemia. This study is a Phase III, open, active-controlled, parallel-group, multi-center study. The total duration of the study will be 30 weeks including screening, treatment and follow-up.

Detailed Description
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The primary objective is to demonstrate non-inferiority of JTZ-951 to darbepoetin alfa.

Official Title
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A Multi-center, Randomized, Open-label, Active-controlled, Parallel-group, Phase III Study to Compare the Efficacy and Safety of JTZ-951 With Darbepoetin Alfa in Anemic Patients With Chronic Kidney Disease Receiving Maintenance Hemodialysis.

Conditions
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Anemia of Chronic Kidney Disease

Intervention / Treatment
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* Drug: JTZ-951
* Drug: Darbepoetin Alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Korean patients aged ≥ 19 years at the time of consent Patients receiving hemodialysis (including hemodiafiltration) consistently three times a week for at least 12 weeks before Scr Visit 1 Patients with TSAT (Transferrin saturation) *2 > 20% or ferritin > 75 ng/mL at Scr Visit 1*1 Patients being treated with ESAs for as least 4 weeks before Scr Visit 1. Patients receiving ESAs at protocol specified dose regimen (i.e., frequency and dose) Patients who have received the same ESA received in most recent week before Scr Visit 1 as during the period between Scr Visit 1 and the day before Week 0 at the same total dose and dosing frequency a week*4. Patients with pre-dialysis Hb levels measured after the maximum interdialytic interval at Scr Visit 1 and Scr Visit 2 (2 weeks after Scr Visit 1) of ≥ 9.5 g/dL and < 12.0 g/dL and a difference (in absolute value) between Scr Visit 1 and Scr Visit 2 of ≤1.0 g/dL Exclusion Criteria: Patients with poorly controlled hypertension Patients with severe hepatobiliary disease Patients with congestive heart failure (NYHA Class III or more) or unstable angina Patients who have developed myocardial infarction, cerebral infarction (excluding asymptomatic cerebral infarction), or venous thromboembolism (pulmonary embolism or deep vein thrombosis) during the period between 24 weeks before Scr Visit 1 and Week 0. Patients who will undergo an ophthalmological procedure (photocoagulation therapy or vitreous surgery) for the treatment of diabetic retinopathy, diabetic macular edema, or age- related macular degeneration during the period between Scr Visit 1 and the end of the study Patients who have undergone erythrocyte transfusion during the period between 12 weeks before Scr Visit 1 and Week 0. Patients who have received protein anabolic hormones, testosterone enanthate, or mepitiostane during the period between 12 weeks before Scr Visit 1 and Week 0. Patients with severe hyperparathyroidism Patients with severe infection, systemic blood disorder (e.g., myelodysplastic syndrome, aplastic anemia, abnormal hemoglobin disease), or hemolytic anemia, or patients with anemia caused by obvious bleeding lesions (e.g., gastrointestinal hemorrhage) Patients who are suspected to have anemia caused by noninfectious chronic inflammatory disease (e.g., connective tissue disease) Patients with malignancy (including hematological malignancy) or previous history of malignancy during the period between 5 years before Scr Visit 1 and Week 0 Patients with previous history of a serious drug allergy such as anaphylactic shock or a hypersensitivity to DA Patients with current or previous history of drug dependence or alcohol dependence Patients who have received another investigational product or have received treatment with an investigational device, or have participated in clinical research involving intervention (medical action beyond the scope of ordinary medical practice intended for research purposes) and received treatment within 12 weeks before Scr Visit 1 Patients who have previously participated in a clinical study of JTZ-951 and received the investigational product Patients who are pregnant, lactating, or may be pregnant (the possibility of pregnancy cannot be ruled out by the PI or the SI based on the results of pregnancy test at Scr Visit 1) Female patients of childbearing potential who have not agreed to use appropriate contraception methods (medically accepted contraceptive methods: surgical sterilization, intrauterine device, condom, diaphragm, etc.) from the time of signing of informed consent to the end of the study, or male patients who have not agreed to use appropriate contraception methods from the start of study treatment to the end of the study. Other patients who, in the judgment of the PI or the SI, are ineligible for the study

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JTZ-951<br>Oral doses once daily | Drug: JTZ-951<br>* Oral tablet Dose adjustments as maintenance dose is allowed according to the result of Hb level.<br>* Other names: enarodustat;|
| Active Comparator: Darbepoetin Alfa<br>Intravenous doses of Darbepoetin Alfa administered once weekly | Drug: Darbepoetin Alfa<br>* Intravenous administration Dose adjustments as maintenance dose is allowed according to the result of Hb level.<br>* Other names: Nesp pre-filled syringe;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in mean Hb level change during the evaluation period from baseline (evaluation period - baseline) between study arm and control arm | Hb level during the evaluation period is the mean of the Hb levels at Week 20, Week 22 and End of Treatment (Week 24 or at discontinuation). | baseline and Week 20 to 24 | 
| Difference in mean Hb level between study arm and control arm during the evaluation period | Hb level during the evaluation period is the mean of the Hb levels at Week 20, Week 22 and End of Treatment (Week 24 or at discontinuation). | baseline and Week 20 to 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with Hb level within the range of baseline ± 1.0 g/dL at Week 4 |  | Week4 | 
| Proportion of subjects with mean Hb level of ≥10.0 g/dL and <12.0 g/dL during the evaluation period |  | Week 20, 22, 24 | 
| Hb level at each Visit |  | Week 2, 4, 8, 12, 16, 20, 22, 24 | 
| Change from baseline in Hb level at each Visit |  | Week 0, 2, 4, 8, 12, 16, 20, 22, 24 |