Double-blind, Multiple Dose Study of Tezepelumab (AMG 157) in Adults With Mild Atopic Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Double-blind, Multiple Dose Study of Tezepelumab (AMG 157) in Adults With Mild Atopic Asthma (NCT01405963), a randomized phase 1 study. The primary outcome is Maximum Percentage Decrease in Forced Expiratory Volume in 1 Second (FEV1) at 3 to 7 Hours Post Allergen Challenge.

2. Clinical Question

The study also aimed to assess early and late asthmatic responses after allergen inhalation challenge, along with safety, tolerability, immunogenicity, and pharmacokinetics. Its listed secondary outcomes include lung-function measures during the early response period and measures of adverse events and anti-tezepelumab antibodies. Those aims provide context for the trial, but they do not replace the primary endpoint or establish what its between-group result was.

3. Trial Design

This was a randomized, quadruple-masked, placebo-controlled, parallel-design phase 1 study. It enrolled adults with mild atopic asthma and was listed as completed. The registry identifies Amgen as the sponsor. The study began on 2011-10-31, and primary completion was recorded as 2013-04-05.

Participants in the tezepelumab arm received 700 mg by intravenous infusion on study days 1, 29, and 57. Participants in the placebo arm received placebo to tezepelumab by intravenous infusion on the same study days. The registry reports enrollment of 31 participants. It does not report the allocation ratio, the number assigned to each arm at randomization, or further details of the randomization procedure.

Allergen inhalation challenges took place on study days 42 and 84. FEV1 was measured before challenge and at specified times after challenge. The primary endpoint focuses on the late asthmatic response, defined in the endpoint description using measurements from 3 to 7 hours after challenge. The record also lists early-response lung-function outcomes and safety-related outcomes.

The record identifies the study as phase 1 and lists safety, tolerability, pharmacokinetics, and pharmacodynamics among its aims. It does not report the detailed statistical plan, the rationale for the enrollment target, or the intended analysis methods for each endpoint. The registry record also does not report whether there were interim analyses or other planned looks at accumulating data.

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: Participants were randomly assigned in a 1:1 ratio to receive tezepelumab or placebo.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants who received at least 1 dose of study drug with available data on each day.

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: Participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Percentage Decrease in Forced Expiratory Volume in 1 Second (FEV1) at 3 to 7 Hours Post Allergen Challenge, measured over Days 42 and 84 at pre-allergen challenge and at 180, 240, 300, 360, and 420 minutes (3-7 hours) post allergen challenge.

The primary endpoint is the maximum percentage decrease in forced expiratory volume in 1 second, or FEV1, from the pre-allergen challenge value during the 3 to 7 hours after challenge. FEV1 is a measure of how much air a person can forcefully exhale in one second. In this study, an allergen challenge was used to induce airway bronchoconstriction, and the fall in FEV1 was used to assess the late asthmatic response.

For each measurement time in the late-response window, the percentage change was calculated relative to the pre-challenge FEV1. The endpoint then selected the largest percentage decrease, or the minimum percentage increase, over that window. The registry describes the endpoint as a mean with standard deviation and identifies percent change as its unit.

In general, using a maximum decrease across a prespecified window can represent the greatest observed lung-function reduction during that phase of a response. It also condenses repeated measurements into a single participant-level measure. That summary depends on the measurements taken and the definition of the time window; it does not describe every change over time. The registry specifies measurements on study days 42 and 84 and at 180, 240, 300, 360, and 420 minutes after challenge, but does not report the group-level endpoint values or a comparison between treatment groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as a continuous measure summarized by a mean and standard deviation. Those labels describe how a measured quantity may be summarized; they do not, by themselves, specify the statistical test or model used to compare treatment groups. The test, model, covariate adjustment, and method for combining measurements across study days are not reported in the registry record.

What does a mean and standard deviation describe?

In general, the mean is the arithmetic average of participant-level measurements in a group. The standard deviation describes the spread of those measurements around the mean. A larger standard deviation indicates more variability among observed values, while a smaller one indicates that values are more closely clustered around the mean. These are descriptive statistics, not a direct estimate of the difference between groups. To interpret a treatment comparison, readers also need the group values and an estimate of the contrast, with its uncertainty.

The primary measure is based on repeated FEV1 measurements after allergen challenge. The registry describes a participant-level maximum percentage decrease over the late-response period. In general, reducing repeated measurements to a maximum captures an extreme value within the defined window. It may be sensitive to the timing and variability of individual measurements. The record specifies the measurement schedule, but does not report the detailed calculation rules for any incomplete measurement series or how repeated challenge-day values entered the analysis.

What does uncertainty mean?

In general, a confidence interval communicates the precision of an estimated effect under the assumptions of the chosen method. It provides a range of effect values compatible with the data and method; it is not a guarantee that the true effect lies in that particular interval. A p-value, if reported, addresses compatibility between data and a specified null model, but does not describe the size or clinical importance of an effect. The registry record does not report a confidence interval or p-value for the primary endpoint. Without a group contrast and its uncertainty, the primary endpoint cannot be interpreted as a precise comparative estimate.

The record states that the primary outcome has several categories or time points and was not reduced to one comparison. That matters because a study can produce multiple estimates when outcomes are assessed at different times or under different definitions. In general, selecting or interpreting results across multiple comparisons can raise the chance of emphasizing an apparently notable result by chance. Appropriate approaches may include defining a primary comparison in advance, adjusting for multiple testing, or presenting results as exploratory. Which approach was used is not reported in the registry record, so no multiplicity adjustment can be attributed to this study.

What can the design establish statistically?

Randomization is intended, in general, to make treatment groups comparable on average with respect to measured and unmeasured characteristics. Masking can reduce the influence of expectations on participant experience, assessment, and analysis. The registry identifies randomized allocation and quadruple masking, but does not give the exact masking roles or the randomization procedure. The design labels alone do not establish that all potential sources of bias were eliminated.

The registry lists a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. It describes effects to detect as fractions of the observed effect and says that non-time-to-event illustrations are expressed as participants per arm for 80% power or other specified power. The numerical planning estimates are not reported in this record. These illustrations are not the study's own design justification and must not be interpreted as observed power. The sample-size justification and the trial's original statistical design assumptions are not reported in the registry record.

In general, a sample-size calculation is a prospective planning exercise: it relates an assumed effect, variability, error rate, and allocation to the amount of information sought. Observed power, by contrast, is not a useful substitute for reading the estimated effect and its uncertainty after a study. Because the primary group results are not reported, neither a recalculation from posted summary statistics nor a numerical assessment of precision is available from the registry record.

How should adverse-event counts be understood?

The registry reports counts of participants affected and numbers at risk for serious and other adverse events. These are descriptive group summaries. In general, a count conveys how many participants met the event definition, while the at-risk count identifies the group base associated with that summary. The record does not report event-level timing, duration, recurrence, severity for other adverse events, exposure-adjusted rates, or an inferential comparison. Those details should not be inferred from participant counts alone.

The record also lists outcomes for anti-tezepelumab antibodies, laboratory values, and several FEV1 summaries. Their inclusion indicates that they were outcome measures, not that results or analysis details are available in the registry record. The number of outcome measures is reported as 19, and the number of analyses as 16. The relationship between those counts and any prespecified testing hierarchy is not reported. Taken together, the design and endpoint definitions explain what the study set out to measure, while the absence of primary estimates and analysis details limits the statistical interpretation of its results.

10. Multiplicity, Missing Data and Analysis Populations

The registry describes a primary outcome assessed at multiple challenge days and measurement times, and explicitly notes that it was not reduced to one comparison. It also lists multiple secondary outcomes, including lung-function summaries, adverse-event measures, laboratory values, and anti-tezepelumab antibodies. The record reports 19 outcome measures and 16 analyses. It does not report a prespecified testing hierarchy, a family of primary comparisons, a multiplicity adjustment, or how results across endpoints and times were intended to be interpreted.

In general, when several comparisons are examined, the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiplicity or the results are interpreted as exploratory. The registry information is not sufficient to determine whether any particular adjustment or interpretive strategy was used. No claim about statistical significance for the primary endpoint can be made from the record because its group results and inferential statistics are not reported.

The primary analysis population is described as participants who received at least 1 dose of study drug with available data on each day. The record does not report how many participants met this definition, how many had missing endpoint measurements, or how missing observations were handled. It also does not report whether participants were analyzed according to randomized assignment, treatment received, or another analysis population for the primary endpoint. The participant counts in the safety summaries should not be assumed to be the primary analysis population.

In general, missing-data methods can affect estimates when participants lack measurements, particularly if missingness is related to outcome or treatment. Methods such as complete-case analysis, imputation, or model-based approaches rely on different assumptions. Which, if any, was used is 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists no participants with serious adverse events among 15 at risk in the placebo group and no participants with serious adverse events among 16 at risk in the tezepelumab 700 mg group. It lists no serious adverse-event terms. These are the serious-event counts recorded in the registry; they do not by themselves establish that the risk of serious events is absent or equivalent between groups.

For other adverse events, the registry records 12 affected participants among 15 at risk in the placebo group and 15 affected participants among 16 at risk in the tezepelumab 700 mg group. These are participant counts, not event counts; the record does not give the number of repeated events per participant or details of their timing. It also does not provide an inferential comparison or uncertainty estimates for these summaries.

Deaths are not reported in the registry record. The available summaries should be read as safety observations from this study, rather than as a complete characterization of possible risks. The registry does not report further details such as adverse-event duration, exposure-adjusted rates, or the clinical narratives underlying the counts.

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

The registry record describes a randomized, masked comparison of tezepelumab 700 mg with placebo in adults with mild atopic asthma. It defines a primary measure based on the maximum percentage decrease in FEV1 during the late response after allergen challenge. It also records adverse-event counts and lists other physiological and safety-related outcomes. These details clarify what the study was designed to assess.

However, the record does not report the primary endpoint results by group or a numerical between-group estimate. It therefore does not show the size, direction, or precision of the primary comparison. No conclusion about whether the groups differed on the primary endpoint can be drawn from the registry information alone. The absence of reported results is not evidence that the groups had the same outcome, nor does it establish a difference.

The safety summaries show that other adverse events were recorded in both groups and that no serious adverse events were recorded among the participants at risk in either group. These are descriptive counts in a study with enrollment of 31. They do not establish comparative safety, rule out uncommon events, or describe event severity and timing in detail. Deaths are not reported in the registry record.

In general, a trial result is best interpreted using its estimated effect, uncertainty, analysis population, and analysis methods together. The registry provides the endpoint definition and population description but does not report the primary estimates, missing-data handling, or statistical plan. The result therefore cannot be assessed for statistical precision or for the effect of analysis choices from this record. The study's phase 1 designation and stated aims provide context, but they do not fill in those missing results.

The record supports a description of the trial's design and measurements, not a treatment recommendation or a claim that tezepelumab does or does not alter the response. The distinction is important: knowing what was measured and how the groups were assigned is not the same as knowing the observed treatment effect.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a study built around repeated physiological measurements after a standardized challenge. The primary outcome reduces measurements across the late-response window to each participant's maximum percentage decrease in FEV1. That choice produces a focused summary, while also making the result dependent on the specified window and measurement schedule.

The randomized, quadruple-masked, parallel design provides a framework for comparing treatment and placebo groups. The registry also identifies a distinct primary analysis population based on treatment exposure and available data on each day. Those design and population details matter because they define which observations a result would represent and how a comparison should be interpreted.

The record also illustrates why endpoint definitions do not substitute for outcome reporting. A clearly described endpoint can be understood conceptually, but the treatment contrast cannot be assessed without group results and uncertainty. Here, the registry does not report the primary endpoint estimates, a confidence interval, or a p-value. It also does not report how multiple time points and outcome measures were handled analytically.

Finally, the safety summaries show the difference between descriptive counts and a statistical comparison. Counts communicate what was recorded in each group, but do not by themselves quantify comparative risk or uncertainty. These distinctions are useful when reading early-phase trials, where the aims include safety and biological measurements and where small enrollment can limit the information available about uncommon events.

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.

The main limitation for interpreting the primary endpoint is that the registry record does not report the group-level means and standard deviations or a direct treatment comparison. There is consequently no reported effect estimate, confidence interval, or p-value from which to judge the size and precision of the result. The record also states that the primary outcome was not reduced to one comparison across its categories or time points.

The endpoint uses measurements from allergen challenges on study days 42 and 84, with repeated measurements during the late-response window. The registry does not report how these challenge days were combined or compared, how an incomplete series of measurements was handled, or what model or test was used. The primary analysis population requires at least 1 dose and available data on each day, but the number meeting that definition and the extent of missingness are not reported.

The statistical plan is not reported in sufficient detail to determine whether covariates were used, whether analyses were adjusted for multiple comparisons, or whether any interim analyses occurred. The sample-size justification is not reported. Although the registry describes general assumptions for planning illustrations, it does not give their numerical estimates or establish that those assumptions were the trial's own design choices.

The safety information is also limited to participant counts. The record does not report event timing, recurrence, duration, exposure-adjusted rates, or an inferential comparison. Deaths are not reported in the registry record. With enrollment of 31, the safety counts alone cannot characterize uncommon events or establish equivalence between groups. These limitations describe what can be learned from the registry entry; they do not establish that additional information was absent from other records.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Double-blind, Multiple Dose Study of Tezepelumab (AMG 157) in Adults With Mild Atopic Asthma — NCT01405963.
• Registry record last updated 2022-10-17; status last verified 2022-03.
• Results first posted 2022-10-17.
• 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 describes a completed randomized, quadruple-masked, placebo-controlled, parallel phase 1 study in adults with mild atopic asthma. Enrollment was 31. Participants received tezepelumab 700 mg or placebo by intravenous infusion on study days 1, 29, and 57. Allergen challenges were conducted on study days 42 and 84.

The primary endpoint was the maximum percentage decrease in FEV1 during 3 to 7 hours after allergen challenge, summarized as a mean with standard deviation. The registry does not report the primary group results or a single comparison. It records other adverse events in 12 of 15 participants at risk in the placebo group and 15 of 16 in the tezepelumab group; no serious adverse events were recorded in either group. The statistical plan, missing-data handling, and sample-size justification are not reported in the registry record.