This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Efficacy and Safety Study to Evaluate MT-6548 in Hemodialysis Subjects Currently Receiving ESAs With Anemia Associated With Chronic Kidney Disease in Japan (NCT03439137), a randomized phase 3 study. The primary outcome is Mean Hb Level of Week 20 and Week 24.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03439137 |
| Phase | Phase 3 |
| Condition | Anemia; Hemodialysis Dependent Chronic Kidney Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 323 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Tanabe Pharma Corporation |
| Results posted | Yes |
2. Clinical Question
Population
Hemodialysis subjects in Japan with anemia associated with chronic kidney disease who were currently receiving erythropoiesis-stimulating agents (ESAs). The primary analysis included subjects who had a hemoglobin measurement at least one visit after baseline.
Intervention
MT-6548. The record also lists MT-6548-matching placebo among the interventions, but does not describe the dosing regimen or how the matching placebo was used.
Comparator
Darbepoetin alfa. Darbepoetin alfa-matching placebo is also listed. Specific dose schedules and treatment adjustments are not reported in the registry record.
Primary question
The trial was intended to demonstrate non-inferiority of MT-6548 compared with darbepoetin alfa using hemoglobin values. The posted primary outcome is the mean hemoglobin level at Week 20 and Week 24, reported in g/dL, with a timeframe up to Week 24. A non-inferiority conclusion requires a prespecified margin and a suitable between-group estimate; these are not reported in the registry record.
The clinical question is therefore about hemoglobin levels during treatment in a defined population already receiving ESAs, rather than about a broad group of people with kidney disease. The primary endpoint focuses on measurements at specified visits, while the registry also lists secondary outcomes concerning later mean hemoglobin levels, values at assessment time points, and the proportion within a target range. Those outcomes address different aspects of hemoglobin over time and do not replace the primary comparison.
3. Trial Design
This was a phase III, randomized, quadruple-masked, parallel-group study. It compared MT-6548 with darbepoetin alfa in hemodialysis subjects with anemia associated with chronic kidney disease in Japan. The registry describes the study as double blind in its official title, while its masking entry specifies quadruple masking. The record does not identify which participant or study roles correspond to each masking level.
The registry lists MT-6548, darbepoetin alfa, and matching placebos for each treatment. That listing is consistent with the possibility of maintaining masking across treatments that may differ in presentation, but the precise administration scheme is not reported in the registry record. The arm descriptions are blank, so details such as dose, route, titration, and treatment schedules cannot be established from the record.
Enrollment was 323. The primary outcome reports 160 subjects for each arm, and the analysis population is described as subjects with at least one post-baseline hemoglobin measurement. These figures describe enrollment and the posted primary analysis; they should not be treated as a complete accounting of participant flow. Reasons for exclusions, withdrawals, and missing measurements are not reported in the registry record.
The study status is completed. The recorded start date is 2018-02-14, and the primary completion date is 2018-12-12. The registry identifies Tanabe Pharma Corporation as the sponsor. Its brief summary states that the study sought to demonstrate non-inferiority using hemoglobin and to evaluate long-term safety. The posted primary endpoint is limited to mean hemoglobin at Week 20 and Week 24, with a timeframe up to Week 24; the registry also lists a later mean hemoglobin outcome at Week 48 and Week 52.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | MT-6548 | Darbepoetin Alfa |
|---|---|---|
| STARTED | 162 | 161 |
| COMPLETED | 120 | 135 |
| NOT COMPLETED | 42 | 26 |
Reasons for not completing this period:
| Reason | MT-6548 | Darbepoetin Alfa |
|---|---|---|
| Adverse Event | 16 | 12 |
| Physician Decision | 0 | 5 |
| Withdrawal by Subject | 14 | 4 |
| Conducting rescue therapy | 2 | 1 |
| Difficult to control Hb | 10 | 2 |
| Initiation of a renal transplant | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: This analysis was performed in subjects who measured Hb at least one visit after baseline.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | MT-6548 | Darbepoetin Alfa | Total |
|---|---|---|---|---|
| Participants analysed | 162 | 161 | 323 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 61 | 68 | 129 |
| Age, Categorical: >=65 years | Participants | 101 | 93 | 194 |
| Sex: Female, Male: Female | Participants | 58 | 52 | 110 |
| Sex: Female, Male: Male | Participants | 104 | 109 | 213 |
| Race/Ethnicity, Customized: Asian (Japanese) | Participants | 162 | 161 | 323 |
| Race/Ethnicity, Customized: Asian (Other) | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Other | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Hb Level of Week 20 and Week 24, measured over Up to Week 24.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | g/dL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean hemoglobin level at Week 20 and Week 24, measured in g/dL. Hemoglobin is a continuous measure, so the result describes the average level for each treatment group rather than a count of subjects meeting a threshold. The registry reports least-squares means and 95% confidence intervals. It specifies an analysis population of subjects who measured hemoglobin at least one visit after baseline.
Using a mean can summarize the overall level of a continuous outcome across participants, while selecting scheduled visits makes the measurement time interpretable in relation to treatment. The Week 20 and Week 24 endpoint is relevant to the stated purpose of assessing hemoglobin during treatment. The record does not explain whether the two visits were averaged for each subject, how repeated measurements were handled, or how the least-squares means were adjusted. Those analytic details are not reported in the registry record.
The posted least-squares mean is 10.61 g/dL for MT-6548, with a 95% confidence interval from 10.45 to 10.76. For darbepoetin alfa, the reported mean is 10.65 g/dL, with a 95% confidence interval from 10.5 to 10.8. These are group-specific estimates. A non-inferiority assessment ordinarily depends on a treatment contrast evaluated against a prespecified margin, not merely on separate group means. The margin and a formal contrast are not reported in the registry record, so the endpoint values alone do not establish the intended non-inferiority conclusion.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome gives a least-squares mean hemoglobin level of 10.61 g/dL for MT-6548 and 10.65 g/dL for darbepoetin alfa. The corresponding 95% confidence intervals are 10.45 to 10.76 and 10.5 to 10.8. These results describe estimated mean levels in the two reported analysis groups. The intervals overlap, but overlap between separate group intervals is not a substitute for a confidence interval for the treatment difference or a formal test of non-inferiority.
The registry frames the study as a non-inferiority trial. To interpret such a trial, readers need the prespecified non-inferiority margin, the estimated treatment contrast, its uncertainty, and the analysis rule used to compare that uncertainty with the margin. The margin and the formal contrast are not reported in the registry record. The outcome entry also gives no p-value or analysis results. Accordingly, the posted group means do not by themselves show whether the non-inferiority criterion was met.
The reported group sizes for this primary analysis are 160 for MT-6548 and 160 for darbepoetin alfa. The stated analysis population includes subjects with at least one hemoglobin measurement after baseline. The record does not report a participant-flow account explaining how many randomized subjects lacked such a measurement, or how many were omitted for other reasons. It also does not state whether this was an intention-to-treat, per-protocol, or another analysis population. That distinction matters in a non-inferiority study because different analysis populations can provide different views of the treatment contrast.
The means are reported as least-squares means rather than as unadjusted arithmetic means. Least-squares means generally arise from a statistical model and can account for terms included in that model. Which terms were included, how the outcome was modeled, and how observations across the two visits contributed to the estimate are not reported in the registry record. The confidence intervals communicate uncertainty around each group estimate under the analysis used, but they do not disclose the model or its assumptions.
The registry lists secondary outcomes for mean hemoglobin at Week 48 and Week 52, hemoglobin at each assessment time point, and the percentage of subjects within the target range at each assessment time point during treatment. Three secondary outcomes are posted, but no analyses are listed. Their results therefore cannot be interpreted from the registry record. The brief summary’s reference to long-term safety describes a study objective, not a numerical safety conclusion.
Overall, the posted primary results indicate similar reported group mean levels at the specified visits, with uncertainty represented by group-specific confidence intervals. That descriptive statement is narrower than an inferential conclusion about equivalence or non-inferiority. Without the treatment contrast, margin, and analysis details, the registry record does not establish whether the trial’s stated confirmatory objective was achieved.
9. Statistical Methods Explained
The primary outcome is continuous: it measures hemoglobin in g/dL and is summarized with a least-squares mean for each treatment group. The registry reports a 95% confidence interval for each mean. In general, a confidence interval is a range of values compatible with the observed data and the statistical model at the stated confidence level. It reflects sampling uncertainty, not the spread of individual hemoglobin measurements. The width of an interval depends on factors such as the amount of information and variability, as well as the model used.
For MT-6548, the reported least-squares mean is 10.61 g/dL, with a 95% confidence interval from 10.45 to 10.76. For darbepoetin alfa, it is 10.65 g/dL, with a 95% confidence interval from 10.5 to 10.8. These intervals pertain to the separate group means. A confidence interval for a between-group difference would answer a different question: it would quantify uncertainty in the contrast between treatments. That contrast is not reported in the registry record.
What does a least-squares mean represent?
In general, a least-squares mean is a model-based estimate of a group mean. Its interpretation depends on the model, the included covariates or factors, and the way repeated measurements are represented. The registry does not report those model details. It therefore is not possible to determine from the posted outcome how the estimates were adjusted, whether the two assessment visits were combined by a particular method, or how within-subject correlation was handled.
What is needed for a non-inferiority interpretation?
In general, a non-inferiority analysis asks whether the treatment contrast is sufficiently compatible with a prespecified acceptable margin. The direction of the contrast and the placement of its confidence interval relative to the margin are central to the conclusion. A small observed difference or overlapping separate confidence intervals is not enough to establish non-inferiority. The registry does not report the margin, a contrast estimate, a confidence interval for that contrast, or a p-value for the primary analysis. A formal non-inferiority interpretation is therefore not available from the posted results.
What does the confidence interval not tell the reader?
In general, a confidence interval is not a range containing a stated proportion of individual outcomes, and it does not quantify every source of uncertainty. Its calculation relies on the analysis method and assumptions. The record’s confidence intervals apply to the group estimates as analyzed; they do not resolve concerns about missing data, the choice of analysis population, or whether the protocol’s non-inferiority assumptions were satisfied. Those details are not reported in the registry record.
How should planning illustrations be interpreted?
In general, a sample-size planning illustration estimates how many participants might be needed under stated assumptions to detect a chosen effect with a selected significance level and power. Such an illustration is not an observed trial result and is not a statement of the study’s actual design justification. The posted planning approach uses a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. The registry record does not report the trial’s own sample-size justification. Any planning illustration based on the observed effect should be treated as conditional on those assumptions, not as observed power or proof that the trial was adequately sized for its non-inferiority objective.
Why can over-dispersion matter?
In general, over-dispersion means that observed variation is greater than a statistical model expects. It can make standard errors too small if the model does not account for the extra variability, leading to confidence intervals that are too narrow. This concept is relevant to outcomes modeled as counts or proportions, but the primary endpoint is a continuous hemoglobin measure. The registry does not report evidence of over-dispersion or a model assessment for the primary endpoint, so no claim about its presence or handling is warranted.
What can be learned from the posted method details?
The record identifies the endpoint type, the group-level summary, the confidence level, the timeframe, and the population rule requiring at least one post-baseline measurement. It does not provide a full statistical analysis plan, model specification, treatment-effect contrast, non-inferiority margin, or analysis diagnostics. Those omissions limit how completely an independent reader can reconstruct or evaluate the inferential method from the registry entry.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three secondary outcomes: mean hemoglobin at Week 48 and Week 52, hemoglobin at each assessment time point, and the percentage of subjects within the target range at each assessment time point during treatment. The primary outcome concerns mean hemoglobin at Week 20 and Week 24. When a study evaluates multiple outcomes or time points, multiplicity can arise because the chance of at least one apparently notable result may increase as more comparisons are considered. In general, a prespecified testing hierarchy or adjustment can address this issue. The registry record does not report a multiplicity strategy, and it lists no analyses for the outcomes.
The primary analysis population is described as subjects with a hemoglobin measurement at least one visit after baseline. This definition indicates that the analysis did not require measurements at every scheduled visit, but it does not explain how incomplete outcome data were handled. The registry does not report the number of missing measurements, reasons for missingness, imputation methods, sensitivity analyses, or a comparison of participants included and excluded from the primary analysis. These details are important because missingness can affect the estimated mean and the reliability of a treatment comparison.
The record also does not identify the primary analysis as intention-to-treat, per-protocol, or another population. In general, non-inferiority trials often need careful consideration of more than one analysis population, because exclusions or protocol deviations may influence apparent similarity between treatments. No such analysis strategy or sensitivity analysis is reported in the registry record. The posted group means should therefore be read as results for the stated population, without assuming how other populations would compare.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| MT-6548 | 41 | 162 | 25.3% |
| Darbepoetin Alfa | 44 | 161 | 27.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| MT-6548 | 2 of 162 |
| Darbepoetin Alfa | 1 of 161 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| MT-6548 | 130 of 162 |
| Darbepoetin Alfa | 131 of 161 |
Most frequent serious adverse event terms
| Event term | Organ system | MT-6548 | Darbepoetin Alfa |
|---|---|---|---|
| Shunt stenosis | Injury, poisoning and procedural complications | 4 of 162 | 4 of 161 |
| Shunt occlusion | Injury, poisoning and procedural complications | 4 of 162 | 3 of 161 |
| Angina pectoris | Cardiac disorders | 1 of 162 | 3 of 161 |
| Pneumonia | Infections and infestations | 3 of 162 | 1 of 161 |
| Cerebral infarction | Nervous system disorders | 1 of 162 | 3 of 161 |
| Peripheral arterial occlusive disease | Vascular disorders | 2 of 162 | 2 of 161 |
| Large intestine polyp | Gastrointestinal disorders | 1 of 162 | 2 of 161 |
| Cardiac failure congestive | Cardiac disorders | 2 of 162 | 0 of 161 |
| Coronary artery stenosis | Cardiac disorders | 1 of 162 | 1 of 161 |
| Myocardial ischaemia | Cardiac disorders | 1 of 162 | 1 of 161 |
Most frequent non-serious adverse event terms
| Event term | Organ system | MT-6548 | Darbepoetin Alfa |
|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 74 of 162 | 73 of 161 |
| Diarrhoea | Gastrointestinal disorders | 25 of 162 | 24 of 161 |
| Shunt stenosis | Injury, poisoning and procedural complications | 20 of 162 | 24 of 161 |
| Contusion | Injury, poisoning and procedural complications | 21 of 162 | 19 of 161 |
| Vomiting | Gastrointestinal disorders | 10 of 162 | 17 of 161 |
| Retinal haemorrhage | Eye disorders | 16 of 162 | 10 of 161 |
| Back pain | Musculoskeletal and connective tissue disorders | 15 of 162 | 11 of 161 |
| Skin abrasion | Injury, poisoning and procedural complications | 9 of 162 | 15 of 161 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 10 of 162 | 11 of 161 |
| Pruritus | Skin and subcutaneous tissue disorders | 12 of 162 | 9 of 161 |
Serious events with the highest arm-level rate: shunt stenosis (2.5%), shunt occlusion (2.5%), angina pectoris (1.9%), cerebral infarction (1.9%), pneumonia (1.9%).
The adverse-event record reports serious adverse events affecting 41 of 162 subjects in the MT-6548 group and 44 of 161 subjects in the darbepoetin alfa group. Other adverse events are reported as affecting 130 of 162 subjects and 131 of 161 subjects, respectively. Deaths are reported as 2 in the MT-6548 group and 1 in the darbepoetin alfa group. These are descriptive counts with the group sizes at risk as recorded; they do not by themselves establish a treatment-related difference or cause.
The listed serious-event terms include shunt stenosis and shunt occlusion, each reported as 2.5%; angina pectoris, cerebral infarction, and pneumonia, each 1.9%; and large intestine polyp, 1.2%. The registry excerpt does not specify which treatment group each listed percentage belongs to, so the terms should not be assigned to a particular group. It also does not provide event onset, duration, severity grading, relatedness assessments, or exposure-adjusted rates in the information.
In general, adverse-event counts depend on how events and affected participants are defined and on the observation period. Comparisons should account for those definitions and exposure, not just compare raw counts. The figures describe what the registry reports; they are not, by themselves, proof that an event was caused by treatment or that the treatments have equivalent safety.
12. What the Result Does, and Does Not, Mean
The primary results report group-level mean hemoglobin estimates at Week 20 and Week 24: 10.61 g/dL for MT-6548 and 10.65 g/dL for darbepoetin alfa. Their respective 95% confidence intervals are 10.45 to 10.76 and 10.5 to 10.8. These estimates describe the recorded primary analysis among subjects with at least one post-baseline hemoglobin measurement. They are not individual-level predictions and do not summarize all possible benefits or risks.
The study’s stated aim was to demonstrate non-inferiority. The posted group means alone do not answer whether that aim was met. A formal conclusion requires a defined non-inferiority margin and a treatment contrast with uncertainty assessed against that margin. Those elements are not reported in the registry record. It would therefore be inappropriate to infer non-inferiority, equivalence, or superiority from the two means or from the overlap of their separate intervals.
The registry also reports adverse-event counts and deaths for the treatment groups. These figures give a descriptive account of affected subjects but do not establish that an event was caused by a treatment. The serious-event terms and percentages are not linked to individual arms in the available entry. In addition, the registry lists secondary hemoglobin outcomes but no corresponding analyses, so those outcomes cannot extend the primary result into a complete account of hemoglobin over the full treatment period.
These findings should be understood within the trial’s stated population and setting: hemodialysis subjects in Japan with anemia associated with chronic kidney disease who were receiving ESAs. The record does not report sufficient details to generalize beyond that population or to reconstruct all aspects of treatment delivery, missing-data handling, or the statistical plan. The result is a registry-reported description of two group means with confidence intervals, not a complete account of the study’s inferential conclusions.
13. Why This Trial Matters Statistically
This study is statistically notable because its stated objective is non-inferiority, while the posted primary outcome presents separate group means and confidence intervals rather than the treatment contrast needed to evaluate that objective. The distinction illustrates a central principle of trial interpretation: descriptive estimates for each arm do not automatically answer a comparative question. A non-inferiority claim depends on a prespecified margin and an analysis that evaluates the contrast in relation to that margin.
The endpoint is a continuous measure summarized as a least-squares mean at specified visits. This makes it important to know how the model combined observations, whether any adjustment was used, and how repeated measurements and missing values were handled. Those details are not reported in the registry record. Without them, readers can describe the posted estimates but cannot fully assess the assumptions underlying their precision.
The analysis population is also relevant. The record specifies subjects with at least one post-baseline measurement, but does not give a full participant flow or identify the population under a standard trial-analysis label. In general, the handling of participants with incomplete follow-up can affect treatment comparisons, particularly when the objective is to establish that one treatment is not unacceptably worse than another.
Finally, the record separates a stated long-term safety objective from the available numerical primary outcome and adverse-event summaries. The posted information supports a careful account of what was measured and counted, while leaving key inferential details unavailable. Recognizing that boundary is essential: a registry entry can describe trial results without containing enough information to verify every aspect of the protocol’s planned statistical conclusion.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
Several trial-specific gaps constrain interpretation. The registry does not report the non-inferiority margin, the primary treatment contrast, a confidence interval for that contrast, or a p-value. It also does not report a statistical analysis plan or identify the primary analysis as intention-to-treat, per-protocol, or another defined population. As a result, the stated non-inferiority objective cannot be evaluated from the posted primary outcome alone.
The least-squares means and confidence intervals are presented without the model specification. Covariates, handling of the Week 20 and Week 24 measurements, assumptions about repeated observations, and diagnostics are not reported in the registry record. The analysis population requires at least one post-baseline measurement, but the record does not explain the participant flow, missing-data pattern, reasons for missingness, or sensitivity analyses.
The trial enrolled 323 subjects, while the primary outcome reports 160 subjects in each arm. The registry does not reconcile those figures or explain exclusions from the analysis. Arm descriptions are blank, and the treatment schedules, doses, titration procedures, and use of matching placebos are not described. The masking entry is quadruple, while the official title describes a double-blind study; the roles masked are not specified.
For safety, the record gives affected-subject counts and selected serious-event terms, but does not provide the group assignment for the listed percentages, event-level details, exposure-adjusted rates, or relatedness assessments in the available information. Secondary outcomes are listed without analyses. The registry also does not report the trial’s own sample-size justification or a multiplicity strategy. These limitations do not negate the posted numbers, but they restrict what can be concluded from them.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety Study to Evaluate MT-6548 in Hemodialysis Subjects Currently Receiving ESAs With Anemia Associated With Chronic Kidney Disease in Japan — NCT03439137.
- Registry record last updated 2026-04-06; status last verified 2026-03.
- Results first posted 2021-04-12.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT03439137 is a completed phase III randomized parallel-group trial sponsored by Tanabe Pharma Corporation. It enrolled 323 hemodialysis subjects in Japan with anemia associated with chronic kidney disease who were currently receiving ESAs. The study compared MT-6548 with darbepoetin alfa and was recorded as quadruple masked. The start date was 2018-02-14, and the primary completion date was 2018-12-12.
The primary outcome was mean hemoglobin at Week 20 and Week 24, reported as least-squares means with 95% confidence intervals. The registry reports 10.61 g/dL for MT-6548 and 10.65 g/dL for darbepoetin alfa. The primary analysis population included subjects with at least one post-baseline hemoglobin measurement. The record lists three secondary outcomes and adverse-event counts, but does not list secondary analyses or the formal comparative statistics needed to assess the stated non-inferiority objective.