Anemia; Hemodialysis Dependent Chronic Kidney Disease
Conditions
Brief summary
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.
Interventions
DRUGMT-6548
Oral tablet
DRUGDarbepoetin alfa
Intravenous administration
DRUGMT-6548-matching placebo
Oral tablet
DRUGDarbepoetin alfa-matching placebo
Intravenous administration
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Hb Level of Week 20 and Week 24 | Up to Week 24 |
Secondary
| Measure | 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 |
Countries
Japan
Contacts
STUDY_DIRECTORGeneral Manager
Tanabe Pharma Corporation
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MT-6548 MT-6548: Oral tablet. The dose was adjusted to 150-600 mg/day according to the pre-specified dose adjustment algorithm.
Darbepoetin alfa matching placebo: Intravenous administration | 162 |
| Darbepoetin Alfa Darbepoetin alfa: Intravenous administration. The dose was adjusted to 5-180 ug/week, 2 weeks or 4 weeks according to the pre-specified dose adjustment algorithm.
MT-6548-matching placebo: Oral tablet | 161 |
| Total | 323 |
Baseline characteristics
| Characteristic | MT-6548 | Darbepoetin Alfa | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 101 Participants | 93 Participants | 194 Participants |
| Age, Categorical Between 18 and 65 years | 61 Participants | 68 Participants | 129 Participants |
| Race/Ethnicity, Customized Asian (Japanese) | 162 Participants | 161 Participants | 323 Participants |
| Race/Ethnicity, Customized Asian (Other) | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 58 Participants | 52 Participants | 110 Participants |
| Sex: Female, Male Male | 104 Participants | 109 Participants | 213 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 162 | 1 / 161 |
| other Total, other adverse events | 130 / 162 | 131 / 161 |
| serious Total, serious adverse events | 41 / 162 | 44 / 161 |
Outcome results
Primary
Mean Hb Level of Week 20 and Week 24
Time frame: Up to Week 24
Population: This analysis was performed in subjects who measured Hb at least one visit after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MT-6548 | Mean Hb Level of Week 20 and Week 24 | 10.61 g/dL |
| Darbepoetin Alfa | Mean Hb Level of Week 20 and Week 24 | 10.65 g/dL |
Secondary
Hb Level at Each Assessment Time Point
Time frame: Up to Week 52
Population: This analysis was performed only in subjects who have Hb data at each visit.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MT-6548 | Hb Level at Each Assessment Time Point | Baseline | 10.73 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 2 | 10.61 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 4 | 10.38 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 6 | 10.24 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 8 | 10.24 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 10 | 10.24 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 12 | 10.43 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 16 | 10.57 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 20 | 10.69 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 24 | 10.65 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 28 | 10.58 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 32 | 10.60 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 36 | 10.49 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 40 | 10.53 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 44 | 10.54 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 48 | 10.50 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 52 | 10.47 g/dL |
| MT-6548 | Hb Level at Each Assessment Time Point | Week 52 (LOCF) | 10.24 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 40 | 10.67 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Baseline | 10.73 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 24 | 10.63 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 2 | 10.85 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 52 (LOCF) | 10.61 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 4 | 10.88 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 28 | 10.66 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 6 | 10.83 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 44 | 10.64 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 8 | 10.84 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 32 | 10.77 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 10 | 10.86 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 52 | 10.63 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 12 | 10.90 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 36 | 10.75 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 16 | 10.80 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 48 | 10.63 g/dL |
| Darbepoetin Alfa | Hb Level at Each Assessment Time Point | Week 20 | 10.65 g/dL |
Secondary
Mean Hb Level of Week 48 and Week 52
Time frame: Up to Week 52
Population: This analysis was performed in subjects who measured Hb at least one visit after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MT-6548 | Mean Hb Level of Week 48 and Week 52 | 10.42 g/dL |
| Darbepoetin Alfa | Mean Hb Level of Week 48 and Week 52 | 10.62 g/dL |
Secondary
Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period
Time frame: Up to Week 52
Population: This analysis was performed only in subjects who have Hb data at each visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 2 | 75.0 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 24 | 75.4 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 10 | 56.7 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 28 | 70.5 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 6 | 58.1 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 32 | 73.3 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 12 | 61.9 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 36 | 67.5 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 4 | 63.7 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 40 | 77.0 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 16 | 68.8 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 44 | 74.6 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 8 | 56.0 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 48 | 72.9 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 20 | 73.6 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 52 | 75.7 percentage of subjects |
| MT-6548 | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Baseline | 81.5 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 52 | 86.5 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Baseline | 78.9 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 2 | 81.3 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 4 | 83.0 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 6 | 84.3 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 8 | 85.4 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 10 | 81.5 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 12 | 86.6 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 16 | 84.6 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 20 | 74.0 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 24 | 75.7 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 28 | 77.3 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 32 | 79.5 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 36 | 78.9 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 40 | 81.6 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 44 | 85.6 percentage of subjects |
| Darbepoetin Alfa | Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period | Week 48 | 79.7 percentage of subjects |