A Phase 2A Study to Evaluate the Safety and Effect on Exercise Challenge Testing of MEDI-528 in Adults With Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 2A Study to Evaluate the Safety and Effect on Exercise Challenge Testing of MEDI-528 in Adults With Asthma (NCT00590720), a randomized phase 2 study. The primary outcome is Incidence of Adverse Events.

2. Clinical Question

The trial focused on adults with stable asthma and exercise-induced bronchoconstriction, a specific population rather than a general asthma population. Its title also identifies exercise challenge testing as an area of evaluation. The registry record lists secondary outcomes concerning anti-drug antibodies and measures of forced expiratory volume in 1 second, including absolute and percent maximum change and area under the curve. Those outcome labels indicate a broader assessment than the primary safety count alone, but the registry entries do not establish the results of those assessments.

The key clinical-research question is therefore descriptive: among participants who received at least one dose, how many experienced any adverse event during the stated follow-up window, and what serious events were reported? The posted counts can describe the participants in each arm. They do not, by themselves, establish whether the observed difference reflects a treatment effect, chance variation, or features of the small trial. The registry record does not report a reliable two-arm estimate for the primary binary endpoint.

3. Trial Design

The study is identified as a phase 2A randomized, double-blind, placebo-controlled trial in adults with stable asthma and exercise-induced bronchoconstriction. It used a parallel-group design. The registry record reports total enrollment of 11 participants and lists a placebo arm with 4 participants and a MEDI-528 50 mg arm with 7 participants. The primary outcome population was defined as participants who received at least one dose of investigational product.

The active intervention was MEDI-528 50 mg, given as a subcutaneous injection twice weekly for 4 weeks. Placebo was administered by the same route and schedule. The official title describes multiple fixed subcutaneous doses and dose escalation, but the posted intervention and arm descriptions identify only the 50 mg MEDI-528 arm and placebo. The record does not report details that would establish additional treatment groups or explain how dose escalation was implemented.

Randomization is intended to assign participants to study arms in a way that reduces systematic differences in baseline characteristics. Double masking is intended to limit the influence of treatment knowledge on participants and study personnel. The registry record identifies those design features but does not report the randomization method, allocation concealment procedures, or precisely who was masked.

The study started in 2008-03, reached primary completion in 2008-12, and is listed as terminated. A reason for termination is not reported in the registry record. Nor is it reported whether termination was related to recruitment, operational considerations, safety, or another circumstance. These design details matter when interpreting a small study: the randomization and masking provide context for the comparison, but the posted record does not provide enough information to reconstruct all trial procedures or determine why the trial ended in this status.

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: Treatment assignments were determined using a block randomization procedure with a 2:1 ratio (MEDI-528:placebo) via an interactive voice response system on Day 0 before study drug administration.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of investigational product (MEDI-528 or placebo).

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 Incidence of Adverse Events, measured over Days 0 - 150.

The primary endpoint is the number of participants who experienced adverse events, including serious adverse events, during Days 0 - 150. It is a binary participant-level outcome: for each participant, the question is whether at least one qualifying event occurred during the stated timeframe. The reported endpoint is a count of participants, not a count of every separate event experienced by each participant.

Safety and tolerability are central concerns in a study evaluating an investigational biological treatment. Counting participants with an adverse event provides a direct summary of how many people experienced an event after receiving study product. Including serious adverse events in the endpoint makes the definition broad; it does not mean that every event counted was serious. The registry also reports serious-event information separately, which helps distinguish the broad any-event count from the narrower serious-event counts.

The primary outcome population includes all participants who received at least one dose of MEDI-528 or placebo. That definition makes exposure part of eligibility for the endpoint population. The record does not report the detailed rules for attributing events, handling participants with incomplete follow-up, or defining the precise analysis dataset beyond that population description.

As a general statistical point, a participant-level binary endpoint is easy to interpret as a count, but the count alone does not express uncertainty around the difference between arms. Such an estimate requires a defined comparison and suitable inferential results. The registry record does not report an estimable two-arm comparison for this endpoint, so the posted counts should be read descriptively rather than as a definitive comparative effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

There are two related but distinct ways to read a binary safety outcome. The first is descriptive: count how many participants in each arm experienced at least one adverse event. The second is inferential: estimate how much the event experience differs between arms and quantify uncertainty around that estimate. The registry record gives the arm-level participant counts for the primary endpoint, but says values were missing or not estimable for a two-arm comparison. Thus, the descriptive information is available while a reported comparative estimate is not.

What does a confidence interval describe?

In general, a confidence interval is a range of values compatible with the observed data under a specified statistical method. For a treatment comparison, it communicates uncertainty about the size and direction of the difference. A narrow interval would indicate greater precision than a wide interval, while an interval spanning many plausible effects would indicate substantial uncertainty. No confidence interval for the primary two-arm comparison is reported in the registry record, so the precision of a comparative effect cannot be assessed from a reported interval.

With small groups, estimates based on a few participants are inherently sensitive to each observed outcome. The primary outcome count is 4 in the placebo arm and 6 in the MEDI-528 50 mg arm, with arm sizes of 4 and 7, respectively. These counts should not be converted into a claim of a dependable difference. A count is not an uncertainty measure, and the record specifically notes that the binary two-arm comparison was missing or not estimable.

Why distinguish counts from events?

The primary endpoint is defined as the number of participants experiencing adverse events, including serious adverse events. This is a participant-level measure, so a participant with more than one event still contributes as a participant who experienced an event. The registry entries do not specify whether or how multiple events were handled in other outcome listings. Separately reported serious-adverse-event counts identify participants with serious events and should not be conflated with the broader any-adverse-event endpoint.

As a general statistical concept, binary-outcome methods compare the frequency of participants with an event against those without an event. The precise method matters, particularly when groups are small or event counts are sparse. Different methods can yield different estimates or uncertainty measures in sparse data. The statistical method used for the primary comparison is not reported in the registry record, and no recalculated comparison is available in the registry entries.

What does randomization contribute?

In general, randomization aims to make assigned groups comparable on average with respect to measured and unmeasured baseline factors. It does not guarantee balance in every realized trial, especially with few participants. Double masking can reduce bias in how participants and study personnel experience, assess, and report outcomes, but masking does not remove random error or replace a clearly specified analysis. The record identifies randomization and double masking but does not report the sequence-generation method, allocation concealment, masking procedures, or the analysis methods used to preserve the randomized comparison.

What can planning calculations tell readers?

Sample-size calculations are planning tools that relate a chosen effect size, significance level, allocation, and statistical method to a proposed study size. They are not a measure of the probability that the observed result is true, and they do not establish the precision of results after a trial. The registry record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial was designed using them. A numerical planning estimate is not reported in the registry record, and the trial's own sample-size justification is not reported.

Any planning illustration based on the observed effect is conditional on that effect and the stated assumptions. It should not be called observed power. In general, such retrospective illustrations can depend strongly on an unstable observed effect, particularly when the study is small. They cannot substitute for a prespecified design justification or for an interval estimate of the actual result.

What is the role of over-dispersion?

Over-dispersion is a general concern for count models when the observed variability exceeds what a chosen model assumes. It is often relevant when analyzing counts of events, especially when participants may experience multiple events. The primary endpoint in this record counts participants with at least one event rather than the total number of events, so its basic form is binary rather than an event-count outcome. Whether any other registry outcome required a model addressing over-dispersion is not reported in the registry record. No such modeling choice should be inferred from the endpoint names alone.

Overall, the methods information supports a cautious reading: identify the primary outcome as a participant-level safety count, distinguish it from the serious-event counts, and recognize that no estimable comparative analysis is reported. The registry does not report enough statistical detail to reconstruct the analysis or independently evaluate its assumptions.

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", "MEDI528 50 mg")
n      <- c(4, 7)
events <- c(4, 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  4  4  100.0  39.8  100.0  51.0  100.0  47.8  99.5
ARM  MEDI528 50 mg  7  6  85.7  42.1  99.6  48.7  97.4  47.3  96.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures and 17 posted secondary outcomes. The secondary outcome descriptions include anti-drug antibodies, absolute and percent maximum change in forced expiratory volume in 1 second, and area under the curve of forced expiratory volume in 1 second. Multiple outcome assessments can raise a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and structure of comparisons. That is a general statistical consideration, not a claim about what occurred in this trial.

The registry record does not report a multiplicity strategy, a hierarchy of outcomes, adjustment procedures, or which secondary outcomes were considered confirmatory. It is therefore not possible to determine whether the reported secondary results, if any, were adjusted for multiple testing or intended as exploratory. The primary endpoint is clearly named, but details of the broader inferential plan are not reported in the registry record.

The primary outcome population is described as participants who received at least one dose of MEDI-528 or placebo. The record does not report the number of randomized participants who may not have received treatment, detailed analysis-population definitions for secondary outcomes, or a complete participant flow. It also does not describe how missing endpoint data were handled, whether follow-up was complete for every participant, or whether any sensitivity analyses were performed.

These omissions matter because missing outcomes can affect both the descriptive counts and a comparison between arms. As a general principle, analyses relying on different assumptions about missing outcomes may lead to different conclusions. No imputation approach, missing-data assumption, or sensitivity analysis is reported in the registry record. The absence of these details should not be mistaken for proof that data were missing; it means that the record does not explain how missingness was assessed or handled.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nuclear magnetic resonance imaging abnormal (14.3%).

The serious-adverse-event figures are participant counts: 0 of 4 participants in the placebo group and 1 of 7 participants in the MEDI-528 50 mg group experienced a serious adverse event, according to the registry listing. These are separate from the broader primary endpoint, which counts participants with any adverse event, including serious adverse events. A serious-event count should not be read as a count of all adverse events or as the total number of event episodes.

The registry identifies Nuclear magnetic resonance imaging abnormal at 14.3% among the top serious-event terms. This is a listed term and percentage; the record details do not give further details about its attribution or clinical context. It should not be interpreted as proof that treatment caused the event.

Because the arm sizes are small, the serious-event counts describe only the participants observed in this trial. They do not provide a precise estimate of how often serious events would occur in a larger population. The registry does not report an estimable comparative analysis for the primary binary endpoint, and no comparative serious-event estimate is stated. The trial is listed as terminated, but the reason for termination is not reported in the registry record; that status alone does not establish a safety-related cause.

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

The result means that the registry records adverse events in 4 participants assigned to placebo and 6 assigned to MEDI-528 50 mg for the primary safety endpoint. It also reports serious adverse events in 0 of 4 placebo participants and 1 of 7 MEDI-528 participants. These observations describe the enrolled and treated groups captured in the record. The primary endpoint covers Days 0 - 150 and includes both adverse events and serious adverse events.

The result does not establish that the treatment caused or prevented any particular event. The counts alone cannot distinguish a real difference in underlying event experience from chance variation, and the record does not report a usable two-arm comparison for the binary primary endpoint. No confidence interval or inferential result for that contrast is given. The findings also do not establish that the groups have equivalent safety profiles; the absence of an estimable comparison is not evidence of equivalence.

The trial enrolled 11 participants and is listed as terminated. The reason for termination is not reported in the registry record. The registry entries do not describe a sample-size justification, a prespecified statistical analysis plan, interim analyses, or procedures for missing data. Those absent details limit the ability to assess how completely the primary question was addressed and how the analyses were planned.

The record also lists secondary outcomes related to anti-drug antibodies and lung-function measures. Their outcome names do not, on their own, establish whether results were favorable, unfavorable, precise, or statistically reliable. The registry entries do not provide results for those measures. Consequently, the responsible interpretation is narrow: the primary participant counts and separate serious-event counts can be described, while broader comparative or mechanistic conclusions are not supported by the available record.

More generally, a small randomized trial can contribute descriptive safety information and help characterize the feasibility and conduct of research in a specific population. It cannot make a sparse set of outcomes precise merely because allocation was randomized or masking was used. Conclusions should remain tied to the endpoints and results actually reported, without extending them to all adults with asthma or to outcomes not summarized in the registry.

14. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between reporting arm-level counts and reporting a comparative analysis. For a binary safety outcome, the number of participants with an event in each arm is an important descriptive result. But a treatment comparison also needs an estimate of the contrast and a measure of uncertainty. The registry record gives the counts while identifying the two-arm binary comparison as missing or not estimable. Readers should therefore resist treating the visible counts as if they were a complete inferential result.

The study also makes the scale of small-trial uncertainty concrete. The arm sizes are 4 and 7, and the primary counts are 4 and 6. In groups of this size, individual outcomes have considerable influence on the observed pattern. Randomization and double masking are valuable design features, but neither can make a small sample large or remove uncertainty about an effect. Statistical interpretation must account for both design strengths and the amount of information the trial can provide.

Another important distinction is between the broad primary endpoint and serious adverse events. The primary outcome includes any adverse event and serious adverse events, while serious-event counts are reported separately. Keeping those definitions clear prevents a broad safety count from being mistaken for a serious-event count, or a participant count from being mistaken for a total event count.

Finally, the record highlights the importance of transparent reporting. Details such as the reason for termination, analysis methods, sample-size justification, multiplicity handling, and missing-data procedures are not reported in the registry record. Those details affect how readers assess completeness, precision, and the intended role of secondary outcomes. The statistical value of a trial record depends not only on the observed numbers but also on whether the methods and limitations are documented well enough for readers to understand what those numbers 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 small enrollment is a central limitation for interpreting the safety counts. The record reports 11 participants overall, with 4 in the placebo arm and 7 in the MEDI-528 50 mg arm. In this setting, a small number of outcomes can strongly shape the observed arm-level pattern. The registry record does not report an estimable two-arm comparison for the primary binary endpoint, so the posted counts do not provide a quantified treatment contrast or its precision.

The status is listed as terminated, but the reason for termination is not reported in the registry record. The record also does not establish whether planned enrollment was completed or whether the study ended earlier than intended. Without that context, termination should be treated as a limitation in interpreting the record, not as evidence of a particular cause.

The title describes multiple fixed doses and dose escalation, while the posted intervention descriptions identify MEDI-528 50 mg and placebo. The record details do not resolve whether other dose groups were planned, used, or omitted from the posted arm descriptions. This limits reconstruction of the full treatment design from the available record.

Other important details are not reported in the registry record: the randomization procedure, masking implementation, statistical analysis plan, sample-size justification, analysis methods, missing-data handling, and multiplicity procedures. A complete participant flow and detailed outcome attribution are also not included in the registry record. The registry lists secondary outcome names, but their results are not stated in the registry entries. Together, these limitations restrict assessment of precision, potential bias, outcome completeness, and the wider interpretation of the trial.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase 2A Study to Evaluate the Safety and Effect on Exercise Challenge Testing of MEDI-528 in Adults With Asthma — NCT00590720.
• Registry record last updated 2014-03-21; status last verified 2014-02.
• Results first posted 2014-03-21.
• 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

NCT00590720 is a phase 2A randomized, double-blind, placebo-controlled, parallel-group study in adults with stable asthma and exercise-induced bronchoconstriction. It enrolled 11 participants and is listed as terminated. The active intervention was MEDI-528 50 mg by subcutaneous injection twice weekly for 4 weeks; placebo was administered on the same schedule.

The primary endpoint was the number of participants experiencing adverse events, including serious adverse events, during Days 0 - 150, among participants who received at least one dose. The posted counts are 4 participants in the placebo arm and 6 in the MEDI-528 arm. Serious adverse events were reported for 0 of 4 placebo participants and 1 of 7 MEDI-528 participants. The registry record notes that a two-arm comparison for the binary endpoint was missing or not estimable.

The study started in 2008-03 and reached primary completion in 2008-12. A reason for termination, detailed analysis methods, sample-size justification, and missing-data procedures are not reported in the registry record. Secondary outcome descriptions include anti-drug antibodies and forced expiratory volume in 1 second measures.