Study to Assess the Effect of Tezepelumab on the Immune Response to Influenza Vaccination in Participants With Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess the Effect of Tezepelumab on the Immune Response to Influenza Vaccination in Participants With Asthma (NCT05062759), a randomized phase 3 study. The primary outcome is Post-vaccination Strain-specific Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rises (GMFRs).

2. Clinical Question

3. Trial Design

The study, identified as NCT05062759, is titled as an assessment of tezepelumab’s effect on the immune response to influenza vaccination in participants with asthma. Its official title describes a multicenter, randomized, parallel-group, placebo-controlled Phase 3b study in adolescent and young adult participants with moderate to severe asthma. The registry lists the phase as Phase 3, allocation as randomized, and masking as triple. The study title uses the term double-blind, while the registry’s masking entry is triple.

The registry reports enrollment of 70 participants and a completed study. The start date was 2021-08-23, and the primary completion date was 2022-03-21. Participants were assigned to tezepelumab or placebo. The tezepelumab schedule was 210 mg subcutaneously at Weeks 0, 4, 8 and 12; the placebo schedule matched those visits. Both groups received a single inactivated quadrivalent seasonal influenza vaccine intramuscularly at Week 12, before the fourth study-intervention dose.

The main comparison concerns antibody response after vaccination, with the primary assessment running from Week 12 to Week 16. The HAI assay was not performed for the H3N2 strain because of its known low haemagglutination effect. The record also lists serum tezepelumab concentrations and immunogenicity as secondary outcomes. It records 10 outcome measures and 14 analyses, but does not report a complete statistical analysis plan or explain how those analyses were organized.

Although the overall enrollment was 70, the primary endpoint analysis population was defined by vaccination, receipt of at least one dose of assigned study intervention, availability of pre- and post-vaccination HAI or microneutralization measurements, and absence of influenza infection before Week 16. The registry’s description of additional criteria ends mid-sentence, so those further criteria are not reported in the registry record. The number of participants meeting the analysis-set definition is also not reported in the registry record.

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: The Screening period was 2 to 3 weeks before randomisation. Patients were randomised in a 1:1 ratio to receive tezepelumab or placebo. All the study assessments were performed as per the Schedule of Activities.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Vaccine immunogenicity analysis set consisted of all randomised patients who received the influenza vaccine plus at least 1 dose of tezepelumab or placebo, had pre and post vaccination HAI or Microneutralization antibody measurements, had no influenza infection prior to Visit 7 (Week 16), and had no protocol deviation, judged to have the potential to interfere with the generation or interpretation of an antibody response.

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: All patients randomised and receiving any study intervention were included in the Full analysis set, irrespective of their CSP adherence and continued participation in the study.

6. Primary Endpoint

The registry lists the primary outcome as Post-vaccination Strain-specific Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rises (GMFRs), measured over From Week 12 to Week 16.

The primary endpoint is post-vaccination, strain-specific hemagglutination inhibition antibody geometric mean fold rise (GMFR), assessed from Week 12 to Week 16. HAI is an antibody assay: in general, it measures the ability of antibodies in a sample to inhibit influenza-related haemagglutination. The endpoint compares antibody measurements before and after vaccination, with the registry expressing the result as a geometric mean fold rise for each strain.

In general, fold-rise endpoints are used to describe change relative to a participant’s baseline antibody measurement, rather than only the post-vaccination concentration. A geometric mean is appropriate for measurements that are positive and are analyzed on a multiplicative scale: taking logarithms turns multiplicative changes into additive changes for analysis, and the result can be expressed back on the original scale. These are general statistical properties, not additional details of the study’s analysis plan.

The endpoint is relevant to the study question because both groups received the same vaccine, while assignment to tezepelumab or placebo differed. Comparing their post-vaccination antibody responses can describe whether the groups’ measured responses differed in this study. It does not, by itself, establish a clinical outcome such as protection from influenza. The registry does not report the strain-specific GMFR estimates, their uncertainty intervals, or a single overall primary comparison. It also states that HAI was not performed for H3N2 because of the known low haemagglutination effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is a geometric mean fold rise in strain-specific HAI antibody measurements between Week 12 and Week 16. The registry identifies geometric mean as the summary parameter and geometric coefficient of variation as the dispersion measure. It does not provide a detailed account of the statistical model, transformations, handling of values below assay limits, or method for comparing the randomized groups.

Why use a geometric mean?

In general, antibody measurements and fold changes are positive and can vary multiplicatively. For multiplicative data, a geometric mean summarizes the central tendency by working on a logarithmic scale and then returning to the original scale. A fold rise describes the post-vaccination measurement relative to the pre-vaccination measurement. This can be useful when the scientific question concerns proportional changes rather than absolute increases. These are general statistical explanations; the specific transformation and inferential procedure used for this endpoint are not reported in the registry record.

What does geometric coefficient of variation describe?

In general, a coefficient of variation describes spread relative to the scale of the measurements. Its geometric form is used with data analyzed on a multiplicative or logarithmic scale. Greater dispersion means participants’ measurements vary more around the geometric mean; lower dispersion means they cluster more closely. The registry names geometric coefficient of variation as the dispersion measure but does not report its values for this endpoint. Without estimates of both central tendency and variability, the size and consistency of the antibody responses cannot be assessed.

How should a group comparison be read?

In general, a between-group contrast for a geometric endpoint may be interpreted on a ratio scale, with the value and its confidence interval indicating the direction, magnitude and precision of the contrast. The exact contrast, model, confidence level, and testing procedure for this trial are not reported in the registry record. The record also does not give a single primary comparison: the endpoint includes multiple strain categories or time points and is not reduced to one comparison. HAI was not performed for H3N2, so that strain does not have an HAI result in the stated endpoint description.

A confidence interval is a measure of uncertainty around an estimate under the specified analysis assumptions. In general, it helps distinguish a precisely estimated contrast from one that remains compatible with a broad range of values. It is not a guarantee that the true value lies in a particular interval, and it does not replace examination of the estimate itself. The primary endpoint confidence intervals are not reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a model assumes. If a model underestimates variability, standard errors can be too small and confidence intervals can be too narrow; statistical tests may then appear more decisive than the data warrant. Appropriate modeling or robust uncertainty estimates can address some forms of over-dispersion, depending on the design and data. The registry record does not report whether over-dispersion was assessed or how variability was modeled for this endpoint. It would therefore be inappropriate to claim that a particular adjustment was used.

What do the planning illustrations mean?

The record describes sample-size planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustrations consider detecting a stated fraction of the observed effect. For outcomes other than time-to-event outcomes, the displayed quantity is participants per arm; time-to-event illustrations instead use total events. These are planning illustrations, not the trial’s own design justification and not observed power. The registry does not report the trial’s sample-size justification. No planning estimate should be read as a count of participants actually analyzed or as evidence that the trial had a particular probability of detecting an effect.

In general, power is a property of a planned statistical test under specified assumptions about an effect, variability, sample size and significance threshold. It is not a measure of whether a result is true, and calculating observed power after seeing the results does not provide a useful substitute for the estimate and its confidence interval. The record’s illustrations are explicitly based on the observed effect; they should be understood only as hypothetical planning calculations under their stated assumptions.

What information is missing about inference?

The registry does not report the primary endpoint estimates, uncertainty intervals, statistical test, model covariates, multiplicity adjustment, interim analyses, or complete analysis plan. These details matter for understanding how strain-specific results were estimated and how multiple outcomes or comparisons were handled. They cannot be inferred from the endpoint name or from the fact that the study was randomized. The analysis population is described only in part, and the number of participants included in it is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint refers to strain-specific HAI antibody GMFRs, while the registry indicates that the outcome has several categories or time points and is not reduced to one comparison. This creates a multiplicity question: when several related outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase if each is assessed separately. In general, a prespecified testing hierarchy or an adjustment for multiple comparisons can help control that issue. The registry record does not report whether any such strategy was planned or used, so no multiplicity adjustment should be assumed.

The vaccine immunogenicity analysis set is described as randomized participants who received vaccine and at least one dose of tezepelumab or placebo, had pre- and post-vaccination HAI or microneutralization measurements, and had no influenza infection before Visit 7 at Week 16. The record’s description ends with an additional incomplete criterion. The remaining criteria and the number of participants meeting the definition are not reported in the registry record.

Missing-data handling is also not described. The record does not state how missing antibody measurements, incomplete visits, or assay-related values were treated, or whether any sensitivity analyses were conducted. In general, excluding participants with missing measurements can affect interpretation if missingness is related to group assignment, participant characteristics, or outcomes. Without participant flow and analysis details, the effect of exclusions or missing measurements cannot be assessed.

The registry lists 10 outcome measures and 14 analyses, but does not explain the analysis hierarchy or identify all confirmatory and exploratory comparisons. Interim analyses and stopping rules are not reported in the registry record. These omissions limit interpretation of statistical evidence across the study’s multiple outcomes.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: stab wound (2.9%).

The registry lists serious adverse events for 35 participants at risk in each group. It reports 0 affected participants in the tezepelumab group and 1 in the placebo group. For other adverse events, it reports 14 affected participants among 35 at risk in the tezepelumab group and 15 among 35 at risk in the placebo group. Deaths are listed as 0 in the tezepelumab group and 1 in the placebo group.

These are descriptive counts. They do not establish that study assignment caused an event, prevented an event, or changed risk. The registry does not report the timing, relatedness, duration, or clinical circumstances needed to interpret individual safety events. It lists Stab wound at 2.9% among the top serious-event terms, but does not give an arm-specific attribution for that term in the reported information.

In general, safety comparisons should be interpreted with attention to the number of participants observed, follow-up time, event definitions, and whether events were judged related to study intervention. The registry’s group counts do not supply all of that context. A difference in a small number of observed events is not, by itself, evidence of a causal difference between groups.

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

This trial was designed to assess whether assignment to tezepelumab was associated with a different antibody response after seasonal quadrivalent influenza vaccination than assignment to placebo. Both groups received the vaccine at Week 12, and the primary assessment was the strain-specific HAI geometric mean fold rise from Week 12 to Week 16. The record also describes a vaccine immunogenicity analysis population based on vaccination, study-intervention exposure, antibody measurements, and absence of influenza infection before Week 16.

The posted registry information does not include the primary endpoint estimates or their uncertainty. Therefore, it cannot establish the direction or size of any difference in antibody response, whether that difference was estimated precisely, or how results varied by strain. The H3N2 HAI assay was not performed because of the known low haemagglutination effect. The registry also does not identify a single summarized primary comparison across the endpoint categories.

In general, an antibody response is a laboratory measure, not the same as a clinical outcome. A change in measured antibody levels alone does not establish how often participants became infected, experienced illness, or had complications. The record’s stated primary endpoint concerns antibody measurements; it does not report a result for protection against influenza or another clinical benefit.

The study’s randomized, placebo-controlled design provides a framework for comparing assigned groups, but design features alone do not reveal the observed effect. The available record also leaves important interpretive details unreported, including the number of participants in the primary analysis set, missing-data handling, and the statistical approach to multiple strain-specific comparisons.

The adverse-event counts offer limited descriptive safety information. The registry reports one serious adverse event and one death in the placebo group, none in the tezepelumab group, and other adverse events in 15 placebo and 14 tezepelumab participants. These counts should not be interpreted as establishing a causal safety difference. The record does not give the context needed to attribute events to study intervention.

Accordingly, the registry record describes what the study set out to measure and reports selected event counts, but does not provide enough primary endpoint results to determine what the antibody comparison showed. The absence of a reported estimate is not evidence that the groups had the same response.

13. Why This Trial Matters Statistically

This study illustrates an important distinction in clinical-trial reporting: a clearly named endpoint is not the same as a reported endpoint result. The registry specifies strain-specific HAI geometric mean fold rises over the interval from Week 12 to Week 16, but does not report the corresponding estimates or their uncertainty. Without those, readers cannot assess either the magnitude of the response or the precision of the between-group comparison.

The study also highlights that a primary endpoint may involve multiple related results. Here, the endpoint is strain-specific, and the registry notes that there are several categories or time points rather than one reduced comparison. Statistical interpretation therefore depends not only on the outcome definition, but also on how comparisons were prioritized and how multiplicity was addressed. That approach is not reported in the registry record.

The analysis population is another key part of the statistical question. The record defines eligibility for the vaccine immunogenicity set using vaccine receipt, exposure to at least one dose of study intervention, availability of pre- and post-vaccination measurements, and no influenza infection before Week 16. However, the description is incomplete and the number analyzed is not reported. Readers cannot determine how much the analysis set differed from the overall enrollment or how missing measurements affected the comparison.

Finally, the safety counts show why descriptive event totals need context. Counts from 35 participants at risk in each group provide a record of observed events, but they do not explain event timing, attribution, or causality. Statistical reporting is strongest when endpoint estimates, uncertainty, analysis populations, missing-data handling, and safety context are presented together. The registry record identifies several of these elements but does not report all of them.

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 trial’s primary question is that the registry record does not report strain-specific GMFR estimates, confidence intervals, or a test result. The primary endpoint has several categories or time points and is not reduced to one comparison. Consequently, neither the direction nor the precision of the primary result can be determined from the reported information.

The HAI assay was not performed for H3N2 because of the known low haemagglutination effect. The record does not report an HAI result for that strain. The vaccine immunogenicity population description is also incomplete: it ends after stating that participants had no influenza infection before Visit 7 at Week 16, followed by an unfinished additional criterion. The number included in the analysis population is not reported in the registry record.

Details needed to assess the analysis are not reported, including the statistical model, handling of assay limits and missing values, multiplicity strategy, and any interim analyses. The registry lists multiple outcomes and analyses without explaining their hierarchy. It also does not report the trial’s sample-size justification. The planning illustrations described in the record are based on the observed effect and should not be confused with the original design rationale or observed power.

Safety information is limited to group counts and a listed serious-event term. Event timing, relatedness, duration, and circumstances are not reported in the registry record. These limitations mean the counts can be described, but not used alone to determine whether study assignment caused a safety difference.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Assess the Effect of Tezepelumab on the Immune Response to Influenza Vaccination in Participants With Asthma — NCT05062759.
• Registry record last updated 2023-06-22; status last verified 2023-06.
• Results first posted 2023-04-21.
• 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.

18. Record Summary

NCT05062759 is a completed randomized, placebo-controlled, parallel-group Phase 3b study of tezepelumab in adolescent and young adult participants with moderate to severe asthma. The registry lists enrollment of 70. Participants received tezepelumab 210 mg or placebo subcutaneously at Weeks 0, 4, 8 and 12; both groups received an inactivated quadrivalent seasonal influenza vaccine at Week 12.

The primary endpoint was strain-specific HAI antibody geometric mean fold rise from Week 12 to Week 16. HAI was not performed for H3N2 because of the known low haemagglutination effect. The primary endpoint estimates and their uncertainty are not reported in the registry record, and the endpoint is not reduced to one comparison.

The registry reports serious adverse events in 0 of 35 participants at risk in the tezepelumab group and 1 of 35 in the placebo group. Other adverse events affected 14 of 35 and 15 of 35 participants, respectively; deaths were 0 and 1. These descriptive counts do not establish causality.