A Phase 1, Randomized, Placebo-controlled, Dose-escalation Safety Study of MEDI4212 in Subjects With IgE >= 30 IU/mL: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 1, Randomized, Placebo-controlled, Dose-escalation Safety Study of MEDI4212 in Subjects With IgE >= 30 IU/mL (NCT01544348), a randomized phase 1 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs).

2. Clinical Question

The central clinical question was whether a single dose of MEDI4212, given at different dose levels and by different routes, was associated with treatment-emergent adverse events or serious adverse events during follow-up through Day 85. The registry record describes a Phase 1 safety study, not a trial designed to establish comparative clinical benefit. Its groups also included placebo and omalizumab.

The study used randomized assignment, double masking, and a parallel-group model. These design features describe how the trial was organized, but the registry record does not report the allocation ratio or details of how randomization and masking were implemented. The clinical question is therefore best read as a descriptive safety question across the listed treatment groups. It is not a question about whether one treatment improves a health outcome relative to another.

3. Trial Design

This was a Phase 1, randomized, double-masked, parallel-group study with an enrollment of 295. Its title and brief summary identify safety evaluation and dose escalation as the focus. The treatment groups included placebo, omalizumab, five subcutaneous MEDI4212 dose levels, and one intravenous MEDI4212 dose level. Each described administration was a single dose on Day 1. The registry record does not report the number assigned to each treatment group in the overall enrollment.

The placebo group received a single dose matched to MEDI4212 given by subcutaneous injection or intravenous infusion. Participants in the omalizumab group received a flexible subcutaneous dose between 150 to 375 mg, based on IgE level and body weight. MEDI4212 groups received 5 mg, 15 mg, 60 mg, 150 mg, or 300 mg subcutaneously, or 300 mg intravenously. The intravenous infusion was described as lasting 120 minutes.

The listed conditions were allergic asthma, atopic dermatitis, allergic rhinitis, and healthy volunteers. The registry record does not report the number of participants with each condition or how participants were distributed across these categories. It also does not report additional details about eligibility beyond the IgE threshold included in the title.

The primary outcome covered treatment-emergent adverse events and treatment-emergent serious adverse events from Day 1 to 85. The safety population was defined as participants who received any amount of investigational product and had safety data available. This population definition matters because it differs conceptually from an analysis of everyone enrolled or everyone randomized. The registry record does not report a full participant-flow account or group-specific denominators for every reported outcome.

The study began in 2012-01, reached primary completion in 2013-06, and is listed as completed. Those dates describe the registry record; they do not provide additional information about follow-up completeness, analysis timing, or the trial’s conduct beyond what is recorded.

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: A total of 295 participants were screened, out of which 209 were screen failures and 86 were randomized.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population included all participants who received any amount of investigational product and had safety data available.

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.

Population: Safety population included all participants who received any amount of investigational product and had safety data available.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs), measured over Day 1 to 85.

The primary endpoint counts participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) during Day 1 to 85. An adverse event was defined as an untoward medical occurrence in a participant who received study drug, without regard to whether it was considered caused by the drug. An event was treatment-emergent if it occurred after study-drug administration through Day 85 and was absent before treatment or worsened relative to the pre-treatment state.

The serious-event definition included events resulting in death, initial or prolonged inpatient hospitalization, a life-threatening experience involving immediate risk of dying, persistent or significant disability or incapacity, or congenital anomaly. An event could also be considered serious for another significant reason. The endpoint therefore separates the broad category of adverse events from the subset meeting the stated seriousness criteria.

Counting participants with events is a useful safety measure because it indicates how many people in each group experienced at least one event within the defined observation period. It does not, by itself, describe the total number of events per participant, event duration, severity among non-serious events, or whether events were judged related to treatment. The registry record gives no single combined numerical result for all TEAEs and TESAEs; it presents serious and other adverse-event counts by group. The number of participants affected is a descriptive measure, not proof that a treatment caused or prevented an event.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary outcome is expressed as the number of participants with events, rather than as a mean, median, or continuous measurement. For a participant-count endpoint, each person is classified according to whether the event definition was met during the stated observation period. This makes the result directly interpretable as a count of people affected, but it leaves out information about how many separate events an affected person experienced. The record reports counts for serious events and other adverse events; it does not give event totals or individual event histories in the posted results.

The distinction between “at risk” and “affected” is important. The at-risk count identifies the participants contributing to the group’s safety result, while the affected count identifies how many met the event category. The posted serious-event counts show no affected participants in any group. For other adverse events, affected counts are given for each group. A count should not be read as a rate unless the denominator and observation period are taken into account. Nor should a count by itself be interpreted as an adjusted comparison.

Why does the safety population definition matter?

The registry defines the safety population as participants who received any amount of investigational product and had safety data available. This makes the endpoint directly relevant to participants with recorded exposure and safety information. It also means that the safety population is not automatically identical to the number enrolled or randomized. The enrollment is 295, but the posted adverse-event groups have their own numbers at risk. The registry record does not report a complete flow of participants from enrollment through treatment and safety follow-up, so the reasons for the group-specific numbers at risk are not established in the record.

How should differences between groups be assessed?

In general, a comparison between treatment groups should account for the number of participants observed in each group, the outcome definition, follow-up, and uncertainty in the estimate. Raw counts can be useful descriptions, but they may be misleading as direct comparisons when group sizes are unequal. General statistical practice can express a binary endpoint as a proportion or compare groups using an effect estimate with a confidence interval. A confidence interval describes the range of values compatible with the data under the method’s assumptions and conveys precision. The registry record does not report confidence intervals, comparative effect estimates, or an inferential analysis for the adverse-event groups.

For sparse safety outcomes, estimates can be imprecise, especially when few participants are observed or few events occur. A zero count is still an observation, but it does not establish absence of risk. General statistical methods for sparse outcomes may use methods suited to small counts rather than relying on large-sample approximations. No such analysis is reported in the registry record, so no method-specific comparative conclusion can be drawn from the posted counts alone.

What does randomization contribute?

Randomized assignment can help balance measured and unmeasured characteristics across groups on average, and double masking can reduce the influence of treatment knowledge on care or reporting. Those are general design advantages, not proof that balance or masking was achieved in practice. The registry record identifies the trial as randomized and double-masked but does not report the allocation ratio, the randomization method, the success of masking, or group-level baseline characteristics. The arms also differ in their assigned intervention and dose, and the registry record does not report a single prespecified pairwise comparison for the safety endpoint.

What can planning calculations tell a reader?

General sample-size calculations illustrate how many participants might be needed under specified assumptions to detect a chosen effect with a stated statistical approach. Such calculations are planning illustrations, not findings from the trial and not observed power. The registry record describes an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also states that the effect to detect is a stated fraction of the observed effect. The record does not report the trial’s own sample-size justification, and no planning result should be treated as evidence that the enrolled study was adequately powered for a particular safety comparison.

More generally, power is a property of a planned design under assumptions, not a retrospective measure that proves whether a result is meaningful. For a safety study with several treatment groups and event categories, the relevant planning assumptions would need to match the intended comparisons and outcome definitions. The registry record does not report such a statistical plan. Consequently, the available counts are best treated as descriptive safety information rather than as a test of a stated treatment-effect hypothesis.

Why are adverse-event definitions consequential?

The endpoint’s definitions determine which observations enter each category. A TEAE is based on its timing relative to study-drug administration and whether it was new or worsened compared with the pre-treatment state. Seriousness is determined by specified clinical consequences or other significance. The definition also states that an adverse event is counted without regard to a possible causal relationship. Thus, the outcome is not a count of events adjudicated as caused by treatment. The record does not provide a separate causality classification or a severity breakdown for the other adverse events.

In general, clear and consistent definitions improve comparability, but interpretation also depends on ascertainment, follow-up completeness, and how missing safety information is handled. Those details are not reported in the registry record. The defined time window is Day 1 to 85, which makes the reported outcome a measure of events within that window; it does not describe events outside it.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint that includes TEAEs and TESAEs and lists secondary outcomes for observed serum concentration, participants exhibiting anti-drug antibodies at any visit, and free IgE serum concentration. The record reports four outcome measures overall, but it does not report a statistical analysis for the listed safety endpoint or other outcomes. It does not report an analysis plan describing how multiple outcomes, dose groups, routes, or pairwise comparisons would be handled. Therefore, whether any multiplicity adjustment was planned or applied is not reported in the registry record.

Multiplicity matters in general when many outcomes or comparisons are examined: the chance of at least one apparently unusual result can increase as the number of tests grows. Methods for addressing this depend on the research question and planned analysis. Without a reported plan or inferential results, the posted counts should be read descriptively rather than as evidence from a set of formal tests.

The registry record defines the safety population as participants who received any amount of investigational product and had safety data available. It does not report how missing safety observations were handled, whether any participants lacked data during the Day 1 to 85 window, or whether follow-up was complete for all participants at risk. The record also does not report reasons for missing data or sensitivity analyses assessing their effect. These omissions limit assessment of whether the observed counts capture all relevant events during follow-up.

Randomization and double masking are recorded design features, but the registry record does not specify an analysis population for treatment comparisons beyond the safety-population definition. It does not report an intention-to-treat analysis, a per-protocol analysis, or a prespecified method for handling participants who received only part of an assigned intervention. Details about allocation concealment, baseline balance, and statistical adjustment are also not reported in the registry record.

11. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event results list zero affected participants in every group. The associated numbers at risk are 17 for placebo, 6 for omalizumab, 3 for MEDI4212 5 mg subcutaneous, 3 for MEDI4212 15 mg subcutaneous, 15 for MEDI4212 60 mg subcutaneous, 18 for MEDI4212 150 mg subcutaneous, 14 for MEDI4212 300 mg subcutaneous, and 8 for MEDI4212 300 mg intravenous. The serious-event terms list is empty.

Zero recorded serious events means none were reported in these groups for the endpoint and observation period described. It does not establish that serious events are impossible, that the risk is zero, or that the groups have equivalent safety. In general, when no events are observed, the available information still has uncertainty, and the amount of information depends in part on how many participants were observed and how completely outcomes were captured. The registry record does not provide uncertainty intervals or a comparative analysis for the serious-event counts.

The record also reports other adverse-event counts: 8 of 17 in placebo, 2 of 6 in omalizumab, 2 of 3 in MEDI4212 5 mg subcutaneous, 1 of 3 in MEDI4212 15 mg subcutaneous, 4 of 15 in MEDI4212 60 mg subcutaneous, 9 of 18 in MEDI4212 150 mg subcutaneous, 7 of 14 in MEDI4212 300 mg subcutaneous, and 6 of 8 in MEDI4212 300 mg intravenous. These are counts of participants with other events, not event totals or judgments of causation. The registry record does not report further details about these events in the listed results.

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

The posted results describe safety events recorded in a Phase 1 study with multiple MEDI4212 dose groups, placebo, and omalizumab. They show zero participants with a serious adverse event in each listed group and report the number of participants with other adverse events by group. The endpoint covers events from study-drug administration through Day 85, and the safety population consists of participants who received investigational product and had safety data available.

These observations do not establish that MEDI4212 is safe or unsafe, and they do not establish whether it is more or less safe than placebo or omalizumab. A count of affected participants does not identify whether an event was caused by treatment, because the endpoint definition includes events without regard to possible causal relationship. The record does not report comparative estimates, uncertainty intervals, or formal tests for the group differences. Without those analyses and relevant context, the raw counts should not be interpreted as a treatment ranking.

The study’s Phase 1 focus and single-dose administration are important context. The posted endpoint is limited to the stated follow-up period; it does not describe events outside Day 1 to 85. The results also do not, by themselves, describe event severity for the other adverse events, repeated-dose experience, or effects on clinical outcomes. The registry record does not report those additional details in the results.

General statistical interpretation distinguishes absence of an observed event from evidence that the event cannot occur. Sparse counts, particularly zero counts, can leave substantial uncertainty about the frequency of an outcome. The group-specific numbers at risk are limited and vary across arms, and the registry record provides no uncertainty estimates to quantify the precision of comparisons. The counts are therefore useful as descriptive safety observations within this study, but they are not a definitive estimate of comparative risk or a substitute for a broader evaluation of safety.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it reports a safety endpoint across several dose groups, routes, and comparators while focusing on a relatively short, defined follow-up window. The design includes randomized assignment and double masking, features that can strengthen a comparison when implemented successfully. At the same time, a reader needs more than the design labels to evaluate how comparable the groups were and how precisely the safety outcomes were estimated.

Its primary outcome is based on participant counts, which are readily understood but do not capture the full structure of adverse-event experience. The distinction between all treatment-emergent adverse events and the serious subset is consequential: serious events are important but may be uncommon, while broader event counts include more occurrences but can combine events of different kinds and clinical importance. The record gives group counts, yet no event-level descriptions or comparative uncertainty estimates are reported.

Multiple arms also raise general design and analysis questions. A dose-escalation study may include a range of treatment exposures, but the registry record does not describe a prespecified trend analysis, dose-response model, or planned set of comparisons. With unequal group-specific numbers at risk and no reported inferential analysis, counts across arms should not be treated as a formal dose-response finding.

The record highlights a broader statistical principle: a safety result is not just a count. Interpretation also depends on the outcome definition, denominator, observation period, missingness, and analytic plan. The registry record supplies a clear endpoint window and safety-population definition, but does not report details of missing-data handling, confidence intervals, or multiplicity procedures. These limits make careful descriptive reading especially important. The posted data can document what was observed in this study without resolving the precision or comparative meaning of those observations.

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 limitations specific to this registry record constrain interpretation. The adverse-event results are presented as group counts, while the group-specific numbers at risk vary. The record does not provide confidence intervals, comparative effect estimates, or a statistical test of differences among the treatment groups. Consequently, the precision of any comparison cannot be assessed from the posted results.

The serious-event counts are zero in each listed group, but the numbers at risk are limited, including groups with 3 participants at risk. A zero count in those groups cannot establish the absence of possible serious events. Conversely, the other adverse-event counts do not provide enough event-level information to assess the types, severity, duration, or possible treatment relationship of those events. The serious-event terms list is empty.

The endpoint timeframe is Day 1 to 85, and the treatment descriptions specify single-dose administration on Day 1. These data therefore do not characterize events beyond the stated window or experience with repeated administration. The registry record does not report completeness of follow-up, missing-data handling, reasons for any unavailable safety data, or a participant-flow account explaining group-specific numbers at risk.

The record identifies randomization, double masking, and a parallel-group model but does not report the allocation method, allocation ratio, baseline characteristics by group, or whether masking remained intact. It also does not report a statistical plan for the primary safety outcome, a prespecified comparative analysis, or procedures for handling multiple outcomes and treatment comparisons. These missing details do not negate the descriptive counts, but they limit assessment of how directly they answer comparative questions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase 1, Randomized, Placebo-controlled, Dose-escalation Safety Study of MEDI4212 in Subjects With IgE >= 30 IU/mL — NCT01544348.
• Registry record last updated 2014-12-30; status last verified 2014-12.
• Results first posted 2014-12-30.
• 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.

18. Record Summary

The registry record describes a completed, randomized, double-masked, parallel-group Phase 1 safety study with enrollment of 295. The listed population includes participants with IgE at least 30 IU/mL and conditions including allergic asthma, atopic dermatitis, allergic rhinitis, and healthy volunteers. Treatment groups received placebo, omalizumab, or a single dose of MEDI4212 at one of several subcutaneous doses or by intravenous infusion.

The primary endpoint counted participants with treatment-emergent adverse events and treatment-emergent serious adverse events from Day 1 to 85. The posted serious-event count was zero in every listed group. Other adverse-event counts are reported by group, but no comparative statistical analysis or uncertainty estimates are reported. The registry record does not report details of missing-data handling, multiplicity procedures, or the trial’s own sample-size justification. The results are best understood as descriptive safety observations for the defined population and follow-up period.