Study to Evaluate the Safety and Efficacy of GSK1278863 in Recombinant Human Erythropoietin (rhEPO) Hyporesponsive Hemodialysis-dependent Chronic Kidney Disease Subjects With Anemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Safety and Efficacy of GSK1278863 in Recombinant Human Erythropoietin (rhEPO) Hyporesponsive Hemodialysis-dependent Chronic Kidney Disease Subjects With Anemia (NCT02075463), a na phase 2 study. The primary outcome is Percentage of Participants Demonstrating an Increase in Hgb of >=1 g/dL (if Baseline Hgb is <9.5 g/dL), or >=0.5 g/dL (if Baseline Hgb is 9.5-<10 g/dL), or Stay Within Target Range and do Not Drop by >0.5 g/dL (if Baseline Hgb is >= 10 g/dL) at Week 16.

2. Clinical Question

The question is not simply whether the average Hgb changed. The primary endpoint classifies each participant according to a rule that depends on their baseline Hgb. Participants with lower baseline values needed to reach a stated increase threshold. Participants starting at higher values were assessed against a target-range and decline criterion. This approach makes the endpoint a percentage meeting a clinical measurement rule, rather than a continuous mean change.

The study was intended to evaluate whether GSK1278863 could increase Hgb or maintain it within a target range during treatment after switching from rhEPO. The registry summary also describes safety and efficacy evaluation over the treatment period. The primary endpoint is at Week 16; the listed secondary outcomes include Hgb measurements and iron-related measures. The record does not report the percentage meeting the primary rule, so the stated question cannot be answered from the posted outcome information.

3. Trial Design

The official title describes a 16-week, Phase 2a, single-arm, multicenter, open-label study. The registry phase is listed as Phase 2. The study has no randomized allocation and no masking, and its model is single group. Enrollment is 15. Its status is terminated. The registry record does not report the reason for termination.

The study schedule described in the registry summary includes a 4-week rhEPO run-in period, a 16-week GSK1278863 treatment period, and a 4-week follow-up period. The treatment arm description says participants received a fixed starting dose of 12 mg once daily orally for the first 4 weeks. From Week 4, the dose was to be adjusted based on Hgb levels and evaluated every 4 weeks until Week 16. The dose-adjustment description is incomplete in the registry record, so no further rule can be stated.

The registry lists GSK1278863 and placebo as interventions, but it describes a single GSK1278863 arm and no concurrent placebo group in the trial design or outcome population. Those entries do not establish a randomized placebo comparison. The listed analysis is therefore interpreted as a within-group description, not as an estimate of a treatment difference against a control group.

The registry lists a start date of 2014-06-11 and a primary completion date of 2016-03-16. It reports 22 outcome measures and 0 analyses. A sample-size justification, formal statistical analysis plan, and reason for the selected enrollment are not reported in the registry record. The dates and design features describe the study structure, but they do not supply the missing endpoint results or explain why the study ended.

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.

Before assignment: Study consisted of run-in period of 4 weeks (wk), 16-wk Treatment Phase and Follow-up period of 4-wk after completion of treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT population: participants who received at least one dose of drug, have a baseline Hgb and at least one corresponding on treatment Hgb assessment.

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Demonstrating an Increase in Hgb of >=1 g/dL (if Baseline Hgb is <9.5 g/dL), or >=0.5 g/dL (if Baseline Hgb is 9.5-<10 g/dL), or Stay Within Target Range and do Not Drop by >0.5 g/dL (if Baseline Hgb is >= 10 g/dL) at Week 16, measured over Week 16.

The primary endpoint is the percentage of participants meeting a baseline-dependent Hgb rule at Week 16. For participants whose baseline Hgb was less than 9.5 g/dL, the rule required an increase of at least 1 g/dL. For baseline Hgb from 9.5 to less than 10 g/dL, it required an increase of at least 0.5 g/dL. For baseline Hgb of 10 g/dL or higher, it required Hgb to remain within the target range and not decline by more than 0.5 g/dL.

This is a binary participant-level outcome: each participant either meets the applicable rule or does not. The percentage expresses how often the defined response occurred in the analyzed population. Using different criteria across baseline ranges recognizes that the endpoint's desired pattern differs according to starting Hgb. It does not, by itself, describe the size of each participant's change, the average change, or how Hgb behaved at every time point.

The endpoint is useful for assessing whether participants met a prespecified response or maintenance criterion at the stated time point. Its interpretation depends on the rule and on who had an available assessment. The record says participants available at the indicated time point were analyzed. It names a 95% confidence interval as the dispersion measure, but the primary percentage and its interval are not reported in the registry record. The target range itself is also not specified in the available endpoint description.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a proportion: the number of analyzed participants meeting the endpoint rule relative to the relevant analyzed group, expressed as a percentage. The rule applies individually using baseline Hgb and the Week 16 assessment. Because the rule has different criteria across baseline ranges, interpretation requires knowing which criterion applied to each participant. The registry record describes the criteria but does not report the number assessed in each baseline range or the resulting overall percentage.

What does a confidence interval contribute?

The primary endpoint names a 95% confidence interval as its dispersion measure. In general, a confidence interval gives a range of estimates compatible with the observed data under the method's assumptions. It helps readers judge precision, which an estimate alone cannot show. A wide interval signals substantial uncertainty; a narrow interval signals greater precision. These are general statistical interpretations, not findings about this study: the estimate and interval bounds are not reported in the registry record.

For a percentage outcome, the interval method matters, particularly when the analyzed group is small or the observed proportion is near an extreme. Different methods can yield different bounds. The registry record does not identify the method used to construct the primary confidence interval, and no interval is posted. The record also does not state whether the endpoint calculation used any adjustment or weighting.

Why does the single-group design matter?

A single-group study can describe what happened to the participants who received the study treatment and had the required measurements. It does not directly estimate the difference between treatment and control. A before-and-after comparison within participants is not the same as a randomized comparison: time trends, participant selection, co-interventions, and measurement patterns can also contribute to observed changes. This is a general design distinction. The registry record does not report a concurrent comparison group or a treatment-effect estimate against placebo.

Open-label status means masking is listed as none. In general, knowledge of treatment assignment can influence behavior, clinical management, or the assessment process, depending on the outcome and trial procedures. Hgb is a measured laboratory outcome, but the record does not specify assessment procedures, central laboratory use, or safeguards against measurement-related bias. Those details are not reported in the registry record.

How should the analysis population be understood?

The primary population is described as an ITT population consisting of participants who received at least one dose, had a baseline Hgb value, and had at least one corresponding on-treatment Hgb assessment. The outcome description separately says participants available at the indicated time point were analyzed. These descriptions define eligibility for the analysis, but the record does not give the number included in the Week 16 endpoint calculation. In general, an analysis that requires an observed assessment can exclude participants who lack that measurement; how such missing observations are handled can affect the interpretation of a percentage.

The record does not describe imputation, a missing-data sensitivity analysis, or assumptions about why participants might lack Week 16 data. It is therefore not possible to assess whether missing measurements could have changed the endpoint estimate. No method for handling participants who discontinued or had measurements outside the stated time point is reported.

What can be inferred from the planning assumptions?

The registry's sample-size assumptions describe a planning illustration based on the observed effect, not the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses a total number of events under the Schoenfeld approach; other outcomes are expressed as participants per arm.

Those assumptions are not evidence that this single-arm study was planned or analyzed as a two-arm comparison. The actual sample-size illustration values, the observed effect used for that illustration, and a prospective sample-size justification are not reported in the registry record. Such planning values are hypothetical illustrations, not observed power. They cannot replace the missing observed endpoint estimate or establish the study's ability to answer its primary question.

Over-dispersion is a general concern when variability in data exceeds what a simple statistical model assumes; if ignored, uncertainty can be understated. The primary endpoint is a participant-level binary outcome, but the registry record does not identify a model that would estimate it or indicate that over-dispersion was assessed. It would be inappropriate to attribute a particular model or correction to the analysis without a reported statistical plan.

Finally, a p-value, if reported, would address compatibility of data with a specified statistical hypothesis under a model; it would not describe the magnitude or precision of the response on its own. No p-value or hypothesis test for the primary endpoint is reported. Because this is a single-arm study and the record does not state a formal null hypothesis, a comparative significance claim cannot be reconstructed from the design description.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("GSK1278863 12 mg QD")
n      <- c(7)
events <- c(2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  GSK1278863 12 mg QD  7  2  28.6  3.7  71.0  8.2  64.1  8.5  65.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures, including the primary Week 16 Hgb response percentage and secondary outcomes. The listed secondary outcomes cover change in Hgb, time with Hgb within, below, and above the target range, achievement of an increase threshold, Hgb within the target range, stopping criteria, and changes in hepcidin, ferritin, and transferrin. The registry record does not report results for these outcomes in the information available for this analysis.

When a study examines multiple outcomes or multiple statistical tests, the chance of at least one apparently notable result can increase. General approaches to address this include identifying a primary outcome in advance, limiting confirmatory claims to a defined testing sequence, or adjusting for multiple comparisons. The registry identifies a primary endpoint, but it does not report a multiplicity procedure, testing hierarchy, or statistical analysis plan. It is not possible to determine whether any adjustment was planned or applied.

Missing-data handling is also not reported. The primary description says participants available at the indicated time point were analyzed, while the ITT population definition requires at least one on-treatment Hgb assessment. The number of participants with Week 16 data, reasons for missing assessments, and methods for handling missing values are not reported in the registry record. Without those details, the potential for missingness to affect the estimated percentage cannot be evaluated.

The registry lists 0 analyses. This should be read as the status of analyses listed in the registry record, not as proof that no analyses were conducted outside the record. No primary estimate, confidence-interval bounds, or p-value is reported in the posted results. A statistical analysis plan, interim-analysis plan, and rules governing any multiplicity adjustment are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute myocardial infarction (6.7%), angina unstable (6.7%), cardiac arrest (6.7%), ventricular tachycardia (6.7%), gastroenteritis viral (6.7%).

The registry safety summary gives a risk denominator of 15 participants for serious adverse events and a count of 9 affected participants. For other adverse events, it gives a risk denominator of 15 and a count of 11 affected participants. These are participant counts in the listed GSK1278863 12 mg QD group. They describe the reported safety summaries and do not establish that an event was caused by treatment.

The listed serious adverse event terms are acute myocardial infarction, angina unstable, cardiac arrest, ventricular tachycardia, viral gastroenteritis, and pneumonia. Each term is reported as 6.7%. The record does not provide further detail about event timing, severity beyond the serious classification, recurrence, relatedness assessment, or the number of events per affected participant. The percentages should be read as registry-reported values, not recomputed from the counts.

The death field is not populated; deaths are not reported in the registry record. This is distinct from a report of zero deaths. The safety group is small, and the study has no concurrent control group described, so these figures do not support a controlled comparison of event rates. They also do not establish whether an event is more or less common than it would be without study treatment.

13. What the Result Does, and Does Not, Mean

The study addresses a focused question: whether participants chronically hyporesponsive to rhEPO, while receiving hemodialysis for chronic kidney disease, meet a baseline-dependent Hgb criterion at Week 16 after switching to GSK1278863. The registry record supplies the endpoint definition and the treatment schedule. It does not supply the primary endpoint result, so the observed proportion and its precision cannot be described.

Even if a percentage were available, it would answer a particular measurement question in the analyzed group. It would not by itself establish the cause of a change, because the described design is single-arm and open-label. Nor would meeting the rule establish that every participant had the same Hgb trajectory: the endpoint reduces each person's Week 16 result to whether a threshold was met. The separately listed outcomes concerning Hgb change and time in the target range would give different views of the data, but their results are not reported in the registry record.

The planned treatment period was 16 weeks, with a 4-week rhEPO run-in and a 4-week follow-up period. The primary endpoint is specifically at Week 16; it does not summarize outcomes after that time. The registry record does not report the duration of follow-up actually available for each participant or the results of the follow-up assessments.

The safety summary records serious and other adverse events in the treated group, but these counts are descriptive. They do not show what would have occurred in a comparable group without GSK1278863. The registry status of terminated does not explain why the trial ended, and it should not be interpreted as a result about efficacy or safety.

Overall, the posted information supports understanding the study's population, design, endpoint, and reported safety counts. It does not support a conclusion about the primary Hgb response, comparative benefit, or causal effect. Those conclusions would require outcome results and, for comparative claims, a suitable comparison design or other evidence beyond this registry description.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary endpoint is not a single common threshold applied to everyone. It uses baseline Hgb to determine which response rule applies: a required increase for participants with lower baseline values, and a maintenance criterion for those starting at higher values. That construction makes the estimand—the quantity the analysis is intended to describe—more specific than a general statement about mean Hgb change. Readers need the rule as well as the percentage to understand what a response means.

The study also illustrates why design and endpoint interpretation must be considered together. A single-arm, open-label study can describe a treatment group's observed course, but without a concurrent control it cannot distinguish treatment effects from other changes over time. A numerical response percentage, even if reported, would not alone establish a causal effect. The comparator status matters as much as the endpoint's definition.

Precision is especially important for a percentage from a group with enrollment of 15. The primary outcome specifies a 95% confidence interval, but neither the estimate nor interval bounds are reported in the registry information. The interval would help show how uncertain the estimate is; the count alone would not be enough to assess that uncertainty. Since the primary result is absent, neither magnitude nor precision can be evaluated.

The record also demonstrates the distinction between a registry's design description and its statistical plan. It lists multiple outcomes and a sample-size planning illustration, but does not report a statistical analysis plan, missing-data procedures, or multiplicity strategy. Those omissions limit assessment of how analyses were specified and interpreted. The stated planning assumptions should not be treated as a prospective justification or as evidence of observed power.

These considerations matter because readers may otherwise mistake an outcome definition for an outcome result, a safety count for a treatment comparison, or a planning illustration for evidence of study capability. Careful statistical reading keeps each claim within what the design and posted results can support.

15. 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.

The registry record does not report the reason the study was terminated. It also does not state whether termination affected recruitment, treatment exposure, or completion of the planned assessments. These unknowns limit interpretation of the enrolled group and available follow-up.

Enrollment was 15, and no comparator group is described for the analyzed arm. The placebo intervention entry does not provide a like-for-like control comparison. Consequently, the design cannot directly estimate a between-group treatment difference. The record does not report randomization, masking, or a control-arm outcome.

The primary endpoint result, its 95% confidence interval, and the number assessed at Week 16 are not reported. The endpoint description says participants available at the time point were analyzed, but does not explain how missing Week 16 assessments were handled. The target Hgb range is not specified in the endpoint description, and the dose-adjustment description is incomplete. These missing details impede full replication of the endpoint and treatment procedures.

The registry lists 22 outcome measures and 0 analyses. It does not report an analysis plan, multiplicity approach, sample-size justification, or interim-analysis procedures. The sample-size assumptions describe a planning illustration, not necessarily the trial's own design, and no illustration results are reported in the information. The serious adverse event summary gives counts and terms, but deaths are not reported in the registry record and event relatedness is not stated in the listed data.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Safety and Efficacy of GSK1278863 in Recombinant Human Erythropoietin (rhEPO) Hyporesponsive Hemodialysis-dependent Chronic Kidney Disease Subjects With Anemia — NCT02075463.
• Registry record last updated 2026-08-04; status last verified 2026-07.
• Results first posted 2017-06-21.
• 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.

19. Record Summary

This is a terminated, single-arm, open-label Phase 2 study of GSK1278863 in hemodialysis-dependent participants with anemia associated with chronic kidney disease who were chronically hyporesponsive to rhEPO. Enrollment was 15. The described schedule includes a 4-week rhEPO run-in, 16 weeks of treatment, and a 4-week follow-up period.

The primary endpoint is the percentage meeting a baseline-dependent Hgb response or maintenance rule at Week 16. Although the endpoint definition specifies a 95% confidence interval, the primary result and interval are not reported in the registry record. The registry lists 22 outcome measures and 0 analyses. It also reports serious and other adverse event counts for the GSK1278863 group; deaths are not reported in the registry record.

The design has no randomized allocation or masking and describes no concurrent comparator for the analyzed arm. The registry record does not report the termination reason, a statistical analysis plan, missing-data procedures, or multiplicity methods. The posted information therefore describes the study question and design but does not permit assessment of the primary Hgb result or a comparative treatment effect.