A First Human Study of a Ferroportin Antibody: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A First Human Study of a Ferroportin Antibody (NCT01330953), a randomized phase 1 study. The primary outcome is Number of Participants With Clinically Significant Adverse Effects.

2. Clinical Question

This is a Phase 1 study in healthy subjects, rather than a trial of treatment for a stated illness. The registry lists safety, tolerability, pharmacokinetics, pharmacodynamics, blood iron levels, and immune reactions among the study purposes. The primary outcome focuses on adverse events; the secondary outcomes include pharmacokinetic measures, change from baseline in serum iron, and formation of antibodies to LY2928057.

The main descriptive question is therefore about the observed number of participants with an event in each assigned group. The posted counts are 7 of 8 for placebo, 6 of 6 for 30 mg, 5 of 6 for 100 mg, 5 of 6 for 300 mg, and 6 of 6 for 1000 mg. Those counts describe the participants assessed in this record. They do not, by themselves, estimate a causal effect or establish how the groups would compare in a larger population.

The registry does not report an inferential comparison for this outcome. The clinical question can be framed as a comparison among the five groups, but the posted results support a descriptive reading only. They do not report uncertainty intervals or an adjusted analysis for the primary outcome.

3. Trial Design

The registry identifies this as a randomized, single-masked, parallel-group Phase 1 study. It enrolled 32 participants and is marked completed. The recorded start was 2011-03, and primary completion was 2011-09. The sponsor is Eli Lilly and Company. These design and status details describe the registry record; they do not supply additional outcome data.

Participants were assigned to placebo or one of four LY2928057 dose cohorts: 30 mg, 100 mg, 300 mg, or 1000 mg. The primary outcome lists 8 participants in the placebo group and 6 participants in each dose group. The arm descriptions specify intravenous administration and describe observation and follow-up through Day 85, with a minimum of 12 weeks of follow-up stated for the dose cohorts. The full allocation procedure and the identity of the party or parties masked are not reported in the registry record.

The primary safety outcome covers baseline through Day 85. Its analysis population is described as all randomized participants dosed with placebo or LY2928057 who provided safety data at least through the Day 8 assessment. The record does not state whether every randomized participant met this criterion, nor does it provide a separate accounting of participants who did not.

The study lists 9 outcome measures and 8 secondary outcomes. Those secondary measures cover pharmacokinetics, serum iron change from baseline, and antibody formation. Although the outcome titles are listed, numerical results for those secondary measures are not reported in the registry record. The number of posted analyses is 0, and no formal comparison results for the primary outcome are reported.

Randomization and a parallel-group structure allow outcomes to be described by assigned group. However, the small group sizes and the absence of reported inferential analyses limit what can be concluded from group-to-group differences in counts. The registry does not report the planned statistical analysis in enough detail to assess its intended handling of comparisons or missing observations.

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

Analysis population for the primary outcome, as defined in the registry: The analysis population included all randomized participants dosed with placebo or LY2928057, and who provided safety data at least up to and including the Day 8 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 Number of Participants With Clinically Significant Adverse Effects, measured over Baseline through Day 85.

The primary endpoint is the number of participants with clinically significant adverse effects, measured from baseline through Day 85. The registry defines a clinically significant effect or event as an adverse event. The endpoint is reported as a count for each group, without a measure of spread because it is a count of participants rather than a continuous measurement.

A participant count is useful for a safety outcome because it records how many people in each group experienced at least one qualifying event under the registry’s definition. It provides a direct description of the number affected within each arm. The accompanying group sizes are important context: the same count has a different descriptive meaning in groups of different sizes, so counts should be read alongside the number of participants assessed.

In general, a binary endpoint reduces each participant’s experience for the endpoint to whether the qualifying event was recorded or not. That makes the outcome straightforward to summarize, but it does not describe event severity, duration, recurrence, or timing unless those details are separately reported. The primary endpoint count also does not give the number of individual events; one participant may have more than one adverse event, but this endpoint counts participants.

The registry record states that a listing of serious and non-serious adverse events is located in the Reported Adverse Event Module. The summary outcome does not provide event types or participant-level details. Thus, its role is to describe the number of participants meeting the broad adverse-event definition over the specified period, not to characterize each event or establish a treatment-related cause.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is binary at the participant level: each participant either contributes to the count of those with a qualifying adverse event or does not. The summary then gives a count for each arm, together with the group size. This is a descriptive approach. It does not, by itself, adjust for differences between groups or quantify statistical uncertainty.

What does a participant count represent?

A participant count records people with at least one event that meets the outcome definition, rather than the total number of event episodes. If a participant has multiple adverse events, the primary outcome as described still concerns whether that participant is counted as having an event. The registry defines a clinically significant effect or event as an adverse event, but does not provide a more detailed rule for determining which events qualify for the primary count.

In general, binary outcomes may be expressed as counts, proportions, or comparisons between groups. A proportion relates the count to the number assessed. Here, the posted results are given as counts and group sizes; no additional proportion or comparative estimate is reported. This explanation is general and does not add a recalculation to the trial’s results.

Why does uncertainty matter?

Any observed count is subject to sampling variability: a different set of participants could produce a different count even under similar study conditions. In general, confidence intervals help convey that imprecision, while hypothesis tests assess compatibility with a specified comparison under stated assumptions. Neither a confidence interval nor a p-value for the primary outcome is reported in the registry record. The posted analyses count is 0, and no two-group comparison is available for this binary endpoint.

General inferential methods for binary outcomes can compare event probabilities or model the event indicator, but the method depends on the study question and analysis plan. The registry record does not report the planned statistical test or model, whether any adjustment was intended, or how a formal comparison across the placebo and dose groups would be structured. It would be inappropriate to assign a method to the sponsor’s analysis when that information is not reported.

How should the group structure be understood?

The study is recorded as randomized and parallel-group, with placebo and four dose cohorts. Randomization is intended, in general, to support fair comparisons by reducing systematic differences in participant characteristics at assignment. It does not guarantee balance in a small study, and the registry provides no baseline characteristics with which to assess balance. The record identifies single masking but does not state who was masked. The dose cohorts are separate groups, so their outcomes can be described individually; no trend analysis or pooled dose comparison is reported.

The primary analysis population includes randomized participants who received placebo or LY2928057 and had safety data at least through the Day 8 assessment. This is the population definition stated for the outcome. The record does not explain how data after Day 8 were handled for participants with incomplete follow-up, whether all eligible participants had Day 85 information, or whether the analysis population differs from the set enrolled. These details matter because an analysis restricted by data availability can differ from an analysis of all randomized participants.

What do the sample-size illustrations mean?

The planning illustration method is described as using the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers effects expressed as a stated fraction of the observed effect. In general, such illustrations explore the number of participants per arm that might be needed to detect a specified effect under those assumptions. They are planning scenarios, not evidence that the trial had a particular probability of finding a result after it was conducted.

The registry does not report the trial’s own sample-size justification, and no numerical sample-size illustration results are reported in the registry record. The calculations should therefore not be read as the original design rationale or as observed power. Observed power is not a substitute for the uncertainty of an estimated effect; confidence intervals and the actual analysis are more informative when reported. In this record, no estimated comparison or uncertainty interval is posted.

There is no need to interpret a continuous-outcome dispersion measure for the primary endpoint, because the endpoint is a participant count. General statistical methods for continuous outcomes might use a mean and a measure of variability, but those summaries are not the form in which this primary safety result is reported. The listed secondary pharmacokinetic outcomes are not accompanied by numerical summaries in the registry record, so their analysis methods and estimates cannot be evaluated from the posted outcome information.

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("Placebo", "30 mg LY2928057", "100 mg LY2928057", "300 mg LY2928057", "1000 mg LY2928057")
n      <- c(8, 6, 6, 6, 6)
events <- c(7, 6, 5, 5, 6)
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  Placebo  8  7  87.5  47.3  99.7  52.9  97.8  51.8  97.2
ARM  30 mg LY2928057  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  100 mg LY2928057  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3
ARM  300 mg LY2928057  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3
ARM  1000 mg LY2928057  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures, including the primary safety endpoint and 8 secondary outcomes. Those secondary outcomes span several kinds of measurement, including pharmacokinetic parameters, change from baseline in serum iron, and antibody formation. When multiple outcomes or comparisons are examined, the chance of obtaining a seemingly notable result by chance can increase; in general, statistical plans may address this through a prespecified hierarchy or multiplicity adjustment. The registry does not report whether such a plan was used.

No formal primary outcome analyses are posted, and the registry does not report p-values, confidence intervals, or adjusted comparisons. The statistical approach to multiple dose groups and multiple secondary outcomes is not reported in the registry record. As a result, there is no basis for describing any multiplicity correction or for interpreting the listed outcomes as a single confirmatory testing program.

The outcome population includes randomized participants who were dosed and provided safety data through at least the Day 8 assessment. This criterion is reported, but the handling of missing Day 85 data and other incomplete follow-up is not reported in the registry record. The record does not state whether missing outcomes were imputed, treated as absent, excluded, or handled in another way. It also does not provide an arm-by-arm accounting of missing primary outcome data.

The stated population definition should therefore be kept distinct from an assumption that all randomized participants contributed complete follow-up. The primary results are counts for the posted groups, but the registry information does not fully explain the relationship between those counts, the randomized participants, and any later missing observations. These omissions limit assessment of the possible effect of missing data and of the robustness of the reported summaries.

There are no posted analyses for the listed secondary outcomes. Their titles indicate what was intended for measurement, but numerical results and analysis details are not reported in the registry record. Thus, multiplicity, missing-data handling, and the relationship between primary and secondary analyses remain unclear.

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 non-serious adverse event terms

The serious adverse event summary reports 0 affected participants in the placebo group, with 8 at risk, and 0 in each LY2928057 group, with 6 at risk in each. These figures describe serious adverse events in the reported groups. The registry’s serious-event summary does not list any serious event terms.

A zero count means that no affected participants are recorded in that group in this summary; it does not establish that the true risk is zero. With the small numbers of participants, the summary has limited ability to characterize uncommon events. The registry record does not provide uncertainty intervals for these serious-event counts or a comparative analysis.

The serious-event figures are separate from the primary outcome counts. The primary outcome counts participants with adverse events under the registry definition, while the serious-event summary concerns serious adverse events. The primary counts are 7 of 8 for placebo, 6 of 6 for 30 mg, 5 of 6 for 100 mg, 5 of 6 for 300 mg, and 6 of 6 for 1000 mg. They should not be mistaken for serious-event counts.

The death values are not reported in the registry record. The adverse-event summary does not establish whether an event was caused by the intervention, and the listed figures do not provide event-level descriptions. The registry directs readers to the Reported Adverse Event Module for listings of serious and non-serious adverse events.

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

The results show the number of participants with an adverse event, as defined for the primary outcome, in each study group during baseline through Day 85. The posted counts range from 5 to 7 across groups, with group sizes of 6 or 8. The separate serious adverse event summary records 0 affected participants in each group. Both summaries are observations from this study’s participants and should be read as such.

These results do not establish that LY2928057 caused or prevented an adverse event. The primary endpoint definition identifies an adverse event, not an event judged related to treatment. Nor do the group counts demonstrate that one dose is safer or less safe than another. The record offers no comparative estimate, uncertainty interval, or formal analysis that would support such a conclusion.

The findings also do not determine how frequently adverse events would occur in a larger or different population. This was a Phase 1 study in healthy volunteers with small groups. Generalizing beyond the enrolled participants requires evidence beyond these descriptive counts. The registry’s listed pharmacokinetic and other secondary outcomes cannot extend the interpretation because their numerical results are not reported in the registry record.

In general, a study can be informative about the conduct of a structured early clinical evaluation while still leaving substantial uncertainty about group differences. The count data are useful for describing the recorded safety observations, but a count alone does not convey precision, account for all sources of bias, or explain whether observed events were related to the assigned intervention. The available record supports a bounded description, not a broad claim about clinical benefit or harm.

Accordingly, the result means that the stated number of participants in each group met the registry’s adverse-event definition in the primary outcome summary, and that no serious adverse event participants are recorded in the serious-event summary. It does not mean that the intervention is free of risk, that there is no difference between groups, or that a particular dose has a proven safety profile.

14. Why This Trial Matters Statistically

This study illustrates the statistical role of descriptive safety summaries in an early-phase, dose-cohort trial. Reporting counts together with the number of participants at risk makes the observed data interpretable at a basic level. In a study with small groups, however, those counts carry substantial uncertainty and should not be mistaken for precise estimates of event frequency.

The design includes placebo and four dose cohorts, which creates several possible descriptive comparisons. The registry record does not report a formal comparison or the statistical plan for handling these groups. That distinction matters: a pattern across dose labels can look informative, but a trend is not established by the ordering of a few counts. Formal analysis and uncertainty estimates would be needed to evaluate comparisons more fully.

The record also highlights the value of clearly distinguishing endpoint definitions. The primary outcome counts participants with adverse events, while the separate serious-event summary counts participants with serious adverse events. These are related but not interchangeable summaries. A reader should also distinguish participant counts from counts of event episodes, and distinguish recorded events from events judged to have been caused by the intervention.

Finally, an outcome list is not the same as a set of numerical results. The record identifies secondary pharmacokinetic, serum iron, and antibody outcomes, but their values and analyses are not reported. Statistical interpretation depends on the information actually reported, including analysis populations, handling of missing data, and uncertainty. Where those details are absent, a careful account should preserve that uncertainty rather than infer a result from the study’s aims or design.

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 primary outcome groups are small: 8 participants in the placebo group and 6 in each dose group. The counts therefore provide limited precision, and the registry does not report confidence intervals or a formal comparison to quantify uncertainty. No claim about group differences or dose trends can be supported by the posted counts alone.

The primary outcome is defined broadly as a clinically significant effect or event being an adverse event. The summary does not describe event type, number of episodes, duration, severity beyond the separate serious-event classification, or attribution to the assigned intervention. Event listings are referenced in another registry module, but the primary summary does not reproduce those details.

The outcome population includes dosed randomized participants with safety data through at least Day 8, whereas the outcome timeframe extends through Day 85. The registry does not report how incomplete follow-up or missing Day 85 information was handled, or provide a complete accounting of participants with missing outcome data. The identity of the masked party, details of allocation procedures, and the trial’s own sample-size justification are not reported in the registry record.

The registry lists secondary outcomes but does not report their numerical results or analysis methods. It also does not report a statistical plan for comparisons across the dose cohorts or for multiplicity. These gaps prevent a broader integrated interpretation of safety and the other stated study aims. The death figures are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A First Human Study of a Ferroportin Antibody — NCT01330953.
• Registry record last updated 2018-07-30; status last verified 2017-10.
• Results first posted 2018-07-30.
• 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

The registry record describes a completed Phase 1 randomized, single-masked, parallel-group study of LY2928057 in healthy volunteers. Enrollment was 32. Participants were assigned to placebo or one of four intravenous dose cohorts: 30 mg, 100 mg, 300 mg, or 1000 mg. The primary outcome was the number of participants with clinically significant adverse effects, defined as adverse events, from baseline through Day 85.

The primary counts were 7 of 8 for placebo, 6 of 6 for 30 mg, 5 of 6 for 100 mg, 5 of 6 for 300 mg, and 6 of 6 for 1000 mg. The serious adverse event summary recorded 0 affected participants in each group. No formal primary outcome comparison, confidence interval, or p-value is reported. Numerical results for the 8 listed secondary outcomes are not reported in the registry record.