Efficacy and Safety Study to Evaluate MT-6548 in Non-dialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan
Condition: Anemia; Non-dialysis Dependent Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia
Intervention: MT-6548; Darbepoetin alfa
Intervention description: Oral tablet; Subcutaneous
Intervention MeSH terms: Darbepoetin alfa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 304.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      For Non-dialysis subjects 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.

      For subjects not currently receiving ESAs, evaluate Hb correction and maintenance effect of
      MT-6548 and for subjects currently receiving ESAs, evaluate Hb conversion and maintenance
      effect of MT-6548
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of CKD

          -  eGFR < 60 mL/min/1.73m^2 during the screening period

          -  Not receiving dialysis for 8 weeks prior to the screening period, and not expected to
             start dialysis during the treatment period

          -  Correction group: Not being treated with ESAs for the recent 8 weeks prior to the
             screening period

          -  Conversion group: 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. Correction
             group: ≥8.0 g/dL and < 11.0 g/dL Conversion group: ≥9.0 g/dL and ≤12.5 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) during 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