A Randomized, Open-label, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 Years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, for Pre-exposure Prophylaxis of COVID-19: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Randomized, Open-label, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 Years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, for Pre-exposure Prophylaxis of COVID-19 (NCT05375760), a randomized phase 2 study. The primary outcome is AEs, SAEs, and AESIs.

2. Clinical Question

3. Trial Design

This was a Phase II, randomized, open-label, multicenter, parallel-group, dose-ranging study sponsored by AstraZeneca. It enrolled adults and pediatric individuals aged 12 years or older with COVID-19 as the condition of interest. The listed enrollment was 251. Randomization assigned participants to one of two AZD7442 schedules; the registry record does not report the allocation ratio or the method used to generate the allocation sequence.

Arm A received 300 mg AZD7442 followed by 600 mg every 3 months, for 5 doses in total. Arm B received 600 mg followed by 1200 mg every 6 months, for 3 doses in total. Both regimens used AZD7442, a combination of tixagevimab and cilgavimab. The design therefore compared two active dosing schedules rather than AZD7442 with placebo or no intervention. Open-label means that masking was not used; the record does not describe additional procedures to reduce awareness of assigned treatment.

The study began on 2022-06-09, and primary completion was recorded as 2023-10-04. Its status is terminated. The safety follow-up timeframe reports an average of 48.85 weeks, shorter than the planned 105 weeks because of FDA's request to halt dosing. This change matters when interpreting the accumulated safety observations: the follow-up period described in the record was shorter than planned, and the listed counts do not represent the original planned observation period.

Secondary outcomes included serum AZD7442 concentrations and changes from baseline in geometric mean neutralizing antibody titers and geometric mean fold rises, assessed using wild-type and pseudoneutralization assays. The record lists those biological outcomes but does not report comparative analysis results for them.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set

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 analysis set: participants who received IMP and classified according to the treatment they actually received.

6. Primary Endpoint

The registry lists the primary outcome as AEs, SAEs, and AESIs, measured over Safety data were recorded from the time of the first IMP administration throughout the study for an average safety follow up time of 48.85 weeks. This was shorter than the planned one of 105 weeks due to FDA's request to halt dosing..

The primary outcome is titled “AEs, SAEs, and AESIs” and is measured as the number of participants. It is intended to evaluate AZD7442 safety and tolerability in the Safety Analysis Set. An adverse event is a safety event recorded during the defined observation period; serious adverse events and adverse events of special interest are separately identified categories. The registry record does not provide the detailed definitions used for these categories or the specific criteria for classifying an event as an event of special interest.

Participant counts are useful for describing how many people had at least one recorded event in a category. They are not the same as counts of all event episodes: a participant with repeated events may still be counted once in a participant-based measure. Counts also do not, on their own, describe severity, duration, timing, relationship to treatment, or the total burden of repeated events. Those details are not reported in the primary outcome summary.

Safety outcomes are used to characterize tolerability and identify potential harms during study observation. They do not measure whether AZD7442 prevents COVID-19. The record lists immunogenicity, pharmacokinetic, and pharmacodynamic outcomes separately, but no efficacy outcome or efficacy comparison is given in the primary outcome information.

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 participants with safety events. A participant-count endpoint records whether a person met the event definition during the observation period. It differs from an event-episode count, which could count repeated occurrences in the same person. The registry record does not specify in the primary outcome description whether every event category is counted as participants with at least one event, nor does it publish the event-level data needed to examine recurrence. The arm summaries should therefore be read as reported participant counts, not as a complete account of all event episodes.

How should the arm summaries be compared?

Arm-level counts can describe the safety experience in each randomized group. A formal comparison would ordinarily pair an effect measure with an assessment of its uncertainty. A confidence interval is a range of values compatible with the data under a specified statistical procedure; it helps readers understand how precisely an effect has been estimated. A hypothesis test addresses how compatible the observed data are with a stated null model. Neither a comparative confidence interval nor a test result is reported in the registry record, so the counts alone do not establish a statistical difference.

Randomization is a design feature intended to make treatment groups comparable on average, including with respect to factors that may affect outcomes. It does not guarantee identical groups, and it does not substitute for a reported analysis. The registry record does not describe an adjusted model, a prespecified contrast, or other inferential procedure for these safety counts. No comparative conclusion should be inferred merely from one arm having a larger or smaller count.

Why does follow-up duration matter?

Participants can only have events recorded while they are under observation. The registry record reports an average safety follow-up of 48.85 weeks and says this was shorter than the planned 105 weeks because of FDA's request to halt dosing. A participant count does not account for differing observation time. In general, analyses of event rates over time may use person-time or time-to-event methods, but the record does not report such an analysis for the primary safety outcome. The average follow-up figure also does not show how follow-up was distributed among participants.

Time-to-event methods generally incorporate when an event occurs and how long participants are observed without an event. Their assumptions and results cannot be assessed without a reported model and relevant data. The record contains no such primary-outcome analysis. It would therefore be inappropriate to reinterpret the posted counts as exposure-adjusted rates or as time-to-event estimates.

What does “recalculated” mean in general?

When an analysis is labelled recalculated, it ordinarily means a simple unadjusted calculation made from posted summary statistics rather than the sponsor's full analysis. Such calculations can be informative as checks, but they may not match an analysis using participant-level data, prespecified covariates, or a different analysis population. No recalculated primary comparison is reported in the registry record, and no sponsor comparative estimate is reported for these counts. The record does not identify a discrepancy between sponsor and recalculated results.

Planning illustrations based on an observed effect are different from results of a trial's original sample-size planning. General sample-size calculations depend on assumptions such as the effect to detect, significance level, allocation, and statistical model. The planning assumptions described for illustrations use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such illustrations are not observed power and do not establish that the original study was designed or powered for a particular contrast. The registry record does not report the trial's own sample-size justification. The primary safety outcome has multiple categories or time points and is not reduced to one comparison in the analysis information.

What cannot be evaluated from the record?

The record lists 7 outcome measures and 0 analyses. It gives secondary outcome topics, including serum AZD7442 concentrations and neutralizing antibody measures, but does not report analysis results for those outcomes. It also does not report a primary safety model, effect estimate, confidence interval, or hypothesis test. As a result, the precision and inferential strength of differences between the regimens cannot be evaluated from the posted summaries.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a safety primary outcome with several categories and time points, along with secondary outcomes covering serum AZD7442 concentrations and antibody responses measured by multiple assays. When a study examines many outcomes or contrasts, the chance of at least one apparently notable result can increase. General approaches to multiplicity include prespecifying a hierarchy of outcomes, adjusting the statistical threshold, or treating analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or a statistical analysis plan.

Missing-data handling is also not reported in the registry record. It does not describe how participants with incomplete follow-up, missing measurements, or discontinuation were handled in the safety summaries or secondary outcomes. The shorter-than-planned average safety follow-up is reported, but the record does not give participant-level follow-up patterns or a method for handling incomplete observation. Without that information, the potential influence of missing or incomplete data cannot be assessed.

The primary outcome identifies the Safety Analysis Set as its population. The record does not give additional details about how participants qualified for that set or whether another population was used for other outcomes. It does not report a modified intention-to-treat or per-protocol analysis population, nor does it describe how protocol deviations were handled. These omissions mean that the populations underlying different outcome summaries cannot be compared from the registry record alone.

Although the study was randomized, the posted information does not include a comparative statistical analysis for the safety outcome. Randomization and endpoint multiplicity are separate issues: randomization concerns assignment, while multiplicity concerns how evidence across multiple outcomes is interpreted. Neither the analysis plan nor multiplicity handling can be inferred from the reported counts.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (1.6%), pneumonia bacterial (1.6%), acute respiratory failure (1.6%), anaemia (0.8%), abscess limb (0.8%).

The serious adverse event figures are participant counts in the Safety Analysis Set. In the arm receiving 600 mg once followed by 300 mg every 3 months, 13 of 124 participants had a serious adverse event. In the arm receiving 1200 mg once followed by 600 mg every 6 months, the count was 10 of 124. These counts do not state how many serious event episodes occurred, whether an individual had more than one event, or how events were judged to relate to AZD7442.

The record separately reports other adverse events for 76 of 124 participants in the first arm and 58 of 124 in the second. Deaths are reported as 0 and 1, respectively. The leading serious-event terms include Pneumonia, Pneumonia bacterial, and Acute respiratory failure at 1.6% each; Anaemia, Abscess limb, and Covid-19 are listed at 0.8% each. These percentages are registry entries and are not a comparative statistical analysis.

Because average safety follow-up was 48.85 weeks rather than the planned 105 weeks, the count totals reflect a shorter observation period than planned. The record does not report an exposure-adjusted analysis, event timing, or a formal comparison between arms. The figures describe recorded events; they do not establish causation or show that one regimen has a different safety profile.

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

The registry record documents a randomized comparison of two AZD7442 dosing schedules and reports participant counts for safety outcomes. Those counts provide a descriptive account of adverse events, serious adverse events, and deaths among the participants in each arm. The result is useful as a record of what was observed during study follow-up, but the available summaries do not quantify the uncertainty around a comparison between arms.

The study was terminated, and the reported average safety follow-up of 48.85 weeks was shorter than the planned 105 weeks because of FDA's request to halt dosing. This context is important: the reported counts reflect the observation that occurred, not the full planned follow-up. The registry record does not provide enough detail to determine how incomplete follow-up affected the ability to detect events or how missing information was handled.

The record does not report a statistical comparison of the primary safety outcome, nor does it provide a confidence interval or test result for a difference. It also does not report detailed event-level information or an assessment of treatment relatedness. Differences in the observed counts should not be treated as proof that either regimen is safer or less safe.

These data do not answer whether AZD7442 prevents COVID-19. The stated primary outcome concerns safety and tolerability, while antibody, concentration, and pharmacodynamic measures are listed separately. No efficacy estimate is reported in the registry record. The trial's randomized design should be distinguished from evidence of a treatment effect: evaluating an effect requires the relevant outcome definition, analysis, and uncertainty estimates, which are not reported for a comparative efficacy question.

In short, the posted results describe safety counts from this study under a shorter-than-planned follow-up period. They support neither a causal attribution of individual events nor a definitive comparative conclusion between dosing schedules.

13. Why This Trial Matters Statistically

This study illustrates why interpreting safety counts requires more than comparing the numbers in two arms. Participant counts are straightforward to read, but they do not convey event recurrence, timing, severity, exposure duration, or statistical uncertainty. When follow-up is shorter than planned, the observation period becomes a key part of the interpretation rather than a background detail.

The randomized, parallel-group design is relevant because it assigns participants to alternative dosing schedules, but the record does not report a formal comparative analysis of the safety outcome. This distinction is important in biostatistics: a trial design can support comparisons, while the posted analysis determines what comparison was actually estimated and how precisely it was estimated. Counts alone cannot answer those inferential questions.

The study also includes multiple outcome domains, including safety, serum drug concentrations, and antibody measures. Multiple outcomes can raise questions about prespecification and multiplicity. The registry record does not report the statistical plan or a strategy for interpreting results across these endpoints. This limits the ability to distinguish confirmatory analyses from exploratory ones.

Finally, termination and shorter-than-planned follow-up affect how the safety record should be read. A careful statistical interpretation separates what was observed from what might have been observed with the planned duration, and separates a descriptive pattern from evidence of a treatment difference. The registry record's level of detail permits a concise description of the counts, but not a definitive comparative inference.

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 registry record gives a limited account of the primary safety analysis. It reports participant counts by arm but does not provide a comparative effect estimate, confidence interval, hypothesis test, or analysis model. The event definitions and rules for classifying adverse events of special interest are not detailed in the primary outcome description. Event timing, severity grading, recurrence, and treatment relatedness are also not reported.

Safety follow-up averaged 48.85 weeks, shorter than the planned 105 weeks after FDA's request to halt dosing. The record does not describe the distribution of follow-up across participants or how incomplete follow-up was handled. Participant counts do not incorporate differing observation time, and no exposure-adjusted safety analysis is reported.

The study was open-label, and the registry record does not describe masking or additional procedures to limit awareness of assigned regimen. The allocation ratio, randomization method, sample-size justification, interim analyses, and statistical analysis plan are not reported in the registry record. A multiplicity strategy and missing-data methods are also not reported. The record lists secondary biological outcomes but does not provide their comparative results.

These limitations constrain interpretation of both the safety summaries and any comparison between dosing schedules. They do not establish that the observed events were caused by AZD7442, and they do not permit conclusions about efficacy against COVID-19.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Randomized, Open-label, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 Years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, for Pre-exposure Prophylaxis of COVID-19 — NCT05375760.
• Registry record last updated 2024-10-23; status last verified 2024-09.
• Results first posted 2024-10-23.
• 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

NCT05375760 is a Phase II randomized, open-label, multicenter, parallel-group, dose-ranging study of AZD7442 for pre-exposure prophylaxis of COVID-19 in adults and pediatric individuals aged 12 years or older. It enrolled 251 participants and compared two AZD7442 regimens, using tixagevimab and cilgavimab. The registry record reports a primary safety outcome based on adverse events, serious adverse events, and adverse events of special interest in the Safety Analysis Set.

The study began on 2022-06-09, had primary completion on 2023-10-04, and is listed as terminated. Average safety follow-up was 48.85 weeks, shorter than the planned 105 weeks because of FDA's request to halt dosing. Serious adverse event, other adverse event, and death counts are reported by arm. Comparative statistical results, detailed missing-data methods, the statistical analysis plan, and the trial's sample-size justification are not reported in the registry record.