Efficacy and Safety Study to Evaluate MT-6548 in Hemodialysis Subjects Currently Receiving ESAs With Anemia Associated With Chronic Kidney Disease in Japan

Study Overview
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Brief Summary
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For hemodialysis subjects currently receiving ESAs with anemia associated with chronic kidney disease, demonstrate non-inferiority of MT-6548 compared to darbepoetin alfa using Hb value and evaluate long-term safety of MT-6548.

Official Title
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A Phase III, Double Blind, Confirmatory Study of MT-6548 Compared to Darbepoetin Alfa in Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan

Conditions
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Anemia; Hemodialysis Dependent Chronic Kidney Disease

Intervention / Treatment
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* Drug: MT-6548
* Drug: Darbepoetin alfa
* Drug: MT-6548-matching placebo
* Drug: Darbepoetin alfa-matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CKD Receiving hemodialysis or hemodiafiltration 3 times a week for more than 12 weeks prior to the screening period, excluding receiving home dialysis or combination of peritoneal dialysis. Being treated with ESAs for the recent 8 weeks prior to the screening period Mean of the two screening Hb levels closest in time to the baseline visit is ≥9.5 g/dL and ≤12.0 g/dL Fluctuation between the two Hb levels closest in time to the baseline visit during the screening period less than 1.5 g/dL Serum ferritin ≥ 100 ng/mL, or TSAT ≥20% during the screening period Folate and vitamin B12 ≥ lower limit of normal during the screening period Exclusion Criteria: Anemia due to a main cause other than CKD: sickle cell disease, myelodysplastic syndrome, bone marrow fibrosis, hematologic malignancy, hemolytic anemia, thalassemia, or pure red cell aplasia Active bleeding or recent blood loss within 8 weeks prior to the screening period RBC transfusion within 8 weeks prior to the screening period Received testosterone enanthate or mepitiostane within 8 weeks prior to the screening period AST, ALT, or total bilirubin >2.5 x upper limit of normal during the screening period Uncontrolled hypertension (diastolic blood pressure >110 mm Hg or systolic blood pressure >180 mm Hg) at the first day of the screening period and Day 1 Ophthalmic examinations during the screening period correspond to either of the following criteria; No available fundal findings Findings indicating the presence of active fundal disease Severe heart failure (New York Heart Association Class IV) Cerebrovascular disorder or acute coronary syndrome (hospitalization due to unstable angina or myocardial infarction), requiring hospitalization due to urgent percutaneous intervention for coronary or heart failure within 12 weeks prior to the screening period Current or history of malignancy. History of malignancy with no recurrence for the recent 5 years is not an exclusion criterion New onset or recurrent event of deep vein thrombosis or pulmonary embolism within 12 weeks prior to the screening period Current or history of hemosiderosis or hemochromatosis History of prior organ transplantation or scheduled organ transplant, or prior transplantation of hematopoietic stem cell or bone marrow Males and females of childbearing potential who are unwilling to use an acceptable method of contraception during the designated period (Males: during the study and 90 days after the last dose, females: during study and 30 days after the last dose) Females who are pregnant or breast feeding, or are predicted to be pregnant

Ages Eligible for Study
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Minimum Age: 20 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MT-6548<br> | Drug: MT-6548<br>* Oral tablet<br>* Other names: AKB-6548;Drug: Darbepoetin alfa-matching placebo<br>* Intravenous administration<br>|
| Active Comparator: Darbepoetin alfa<br> | Drug: Darbepoetin alfa<br>* Intravenous administration<br>Drug: MT-6548-matching placebo<br>* Oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Hb Level of Week 20 and Week 24 |  | Up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Hb Level of Week 48 and Week 52 |  | Up to Week 52 | 
| Hb Level at Each Assessment Time Point |  | Up to Week 52 | 
| Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period |  | Up to Week 52 |