Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines (NCT05973006), a randomized phase 3 study. The primary outcome is Participants With Solicited Local and Systemic AEs for 7 Days Following Vaccination.

2. Clinical Question

The clinical question is a comparison of safety after vaccination, with the two vaccine formulations assigned to separate groups. The registry also identifies neutralizing antibody and IgG outcomes, including measurements against Omicron XBB.1.5 and the ancestral Wuhan strain. Those outcomes address immunogenicity, a distinct question from the primary safety endpoint.

The primary endpoint is stated as participants with solicited local and systemic adverse events for 7 days following vaccination. However, the posted record does not present that endpoint as one simple, overall comparison in the information. The tables and plots on this page should therefore be read alongside their labels: the serious adverse event counts are not themselves a substitute for the solicited local and systemic endpoint.

The registry describes the trial as randomized and double-blinded. These design features are intended to support a fair comparison by assigning participants to vaccine groups and limiting knowledge of group assignment during the study. The posted record does not report the detailed procedures used to carry out randomization or maintain masking.

3. Trial Design

This is a Phase 3, randomized, double-blinded, parallel-group study of SARS-CoV-2 rS vaccines in adolescents previously vaccinated with mRNA COVID-19 vaccines. The registry lists an enrollment of 400. It describes two vaccine groups: a monovalent NVX-CoV2601 formulation and a bivalent NVX CoV2373 + NVX-CoV2601 formulation.

The monovalent group received NVX-CoV2601, described as 5 μg of antigen with 50 μg of Matrix-M adjuvant. The bivalent group received 5 μg of each antigen, with a total of 50 μg of Matrix-M adjuvant. The official title identifies the study as an evaluation of safety and immunogenicity of Omicron subvariant and bivalent SARS-CoV-2 rS vaccines.

Randomization means that assignment to a group is determined by a chance-based process rather than by a participant’s or investigator’s choice. In general, this can help make groups comparable with respect to factors that could influence outcomes. Double blinding means that assignment is concealed from participants and relevant study personnel as described in the registry summary; the registry record does not detail who remained blinded or how masking was maintained.

The study began on 2023-08-16, has a primary completion date of 2024-04-01, and is listed as completed. These dates and status describe the study record; they do not, by themselves, indicate the direction or strength of any safety or immunogenicity result.

The registry lists 10 outcome measures and identifies neutralizing antibody titers, geometric mean fold rise, and IgG measurements among the secondary outcomes. The record does not report a detailed statistical analysis plan, the rationale for the planned enrollment, or the methods used to choose the enrollment target. Those details are 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.

Overall Study

Reasons for not completing this period:

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 Participants With Solicited Local and Systemic AEs for 7 Days Following Vaccination, measured over Day 7.

The primary endpoint concerns participants with solicited local and systemic adverse events during the 7 days following vaccination. A solicited event is an event specifically sought during safety monitoring, rather than one captured only through open-ended reporting. Local and systemic events refer to different kinds of symptoms or reactions, but the registry information does not list the individual events or their separate results.

Counting participants with an event is a binary-outcome approach: each participant is classified according to whether the defined event occurred. This can provide an accessible summary of how many participants experienced a monitored event in each group. It does not describe the full pattern of symptoms, their severity, duration, or timing unless those details are separately reported.

The endpoint is used to assess safety over the stated follow-up period after vaccination. The focus on solicited events provides a defined observation window and a structured way to collect information soon after vaccination. The posted record describes the endpoint as an assessment of overall safety, but the outcome summary is not reduced to a single comparison. The registry record does not report a single combined estimate for this primary endpoint in the material.

Serious adverse events are a separate safety category from the solicited local and systemic events specified in the primary endpoint. The serious-event counts shown in the safety section should not be read as the primary endpoint’s complete result. The record also does not report how the primary outcome categories were combined or how any missing event reports were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods described in the registry record are randomized allocation, double blinding, and a parallel-group design. In a parallel-group trial, participants are assigned to one group and followed in that group, rather than switching between the study interventions. Random assignment is intended, in general, to reduce systematic differences between groups at the start of a trial. Blinding is intended, in general, to limit the influence that knowledge of treatment assignment could have on reporting or assessment. The registry does not report the detailed procedures used for either feature.

What does a binary endpoint represent?

The primary outcome is expressed as the number of participants with solicited local and systemic adverse events during the stated 7-day period. This is a binary outcome because each participant is classified as having or not having the specified event, according to the endpoint definition. The registry record gives the endpoint title and purpose, but does not provide a single overall comparison for it in the information.

In general, binary outcomes can be summarized as event counts and as proportions of participants assessed. The counts and denominators shown in the safety data allow the reader to see how many participants were included in the reported risk group and how many had the recorded event. This page does not calculate new proportions or comparisons from those entries. Any displayed summaries should be interpreted according to their own outcome definitions, not assumed to represent the primary solicited-event endpoint.

Why distinguish counts from comparisons?

A count describes the observed events in a group. A comparison asks how the outcome differs between groups and how much uncertainty surrounds that difference. In general, inferential comparisons may use confidence intervals and statistical tests, selected according to the outcome and the analysis plan. The registry record does not report such inferential results for the posted adverse event counts. Consequently, descriptive differences in counts should not be presented as statistically established effects.

In general, a confidence interval helps communicate precision, while a hypothesis test evaluates compatibility with a specified null hypothesis under stated assumptions. Neither supplies a clinical interpretation on its own. No confidence interval or test result for the safety counts is reported, and the record does not state the analysis model or comparison that would be needed to interpret such results.

How should the safety categories be kept separate?

The primary endpoint concerns solicited local and systemic adverse events over a defined period. The registry also posts serious adverse event counts and other adverse event counts. These labels represent distinct summaries. Seriousness, whether an event was actively solicited, and whether an event is included in a composite endpoint are separate classification questions in general. The record does not give enough detail to equate these categories or to reconstruct the primary endpoint from the serious-event counts.

The list of serious adverse event terms is another form of descriptive reporting. A term and its posted percentage indicate that the registry lists that term at that value. They do not, by themselves, identify causation, the timing of an event, or whether an event was judged related to vaccination. Those details are not reported in the registry record.

What can the sample-size section tell us?

The sample-size section is a planning illustration, not a report of the trial’s design justification and not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. The sample-size assumptions describe a calculation based on observed data; they do not show that the trial was originally planned using that effect or those assumptions.

In general, sample-size planning asks how much information a study would need to detect a specified effect under chosen assumptions. It depends on the outcome, the target effect, the analysis method, and other design choices. A planning illustration cannot establish that a trial had adequate power for every endpoint, and it is not evidence that an effect was observed. The registry’s own sample-size justification is not reported in the registry record. The posted sample-size illustrations should therefore be read as hypothetical planning scenarios, not as trial results.

Why do analysis details matter?

A statistical plan specifies how outcomes will be summarized and compared, including which participants are included, how missing observations are handled, and whether adjustments are made when several outcomes are examined. These decisions affect interpretation. The registry summary lists 10 outcome measures and several immunogenicity outcomes, but it does not provide a statistical analysis plan or analysis records. The exact model, any covariate adjustment, and the inferential procedure are not reported in the registry record.

For event counts, general concerns can include incomplete follow-up, differences in time under observation, and rare outcomes that provide limited information about precision. These are methodological considerations, not claims about what occurred in this study. The record does not describe those issues in enough detail to assess them. Readers should consequently distinguish the posted descriptive data from analysis features that the registry does not document.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures, including safety and immunogenicity outcomes. When a study examines multiple outcomes, there is a general statistical concern that repeated testing can increase the chance of at least one apparently notable result arising by chance. A prespecified hierarchy or an adjustment procedure can address aspects of this issue, but the registry record does not report whether either was planned or used.

The registry summary lists no analysis records. It does not report a statistical analysis plan, the handling of multiple comparisons, or which outcomes were considered primary for formal inference beyond the endpoint description. Any multiplicity strategy is therefore not reported in the registry record. The immunogenicity outcomes should not be treated as confirmatory findings without the analysis context needed to support that interpretation.

The record also does not describe the analysis populations, such as which participants were included in each outcome analysis or whether exclusions were made after randomization. The approach to missing outcome data, incomplete follow-up, and participants with unavailable measurements is not reported in the registry record. No imputation method or sensitivity analysis is described.

Interim analyses and any stopping rules are not reported in the registry record. Neither is the sample-size justification for the trial’s planned enrollment. These omissions do not establish that such procedures were absent; they limit what can be concluded from the registry information. For readers, the practical distinction is between details explicitly documented and details that remain unavailable.

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: suicidal ideation (1.6%), adjustment disorder with anxiety (0.5%), adjustment disorder with depressed mood (0.5%), depression (0.5%), post-traumatic stress disorder (0.5%).

The serious adverse event figures are reported by group: 7 among 190 at risk in Group-A NVX-CoV2601 and 1 among 210 at risk in Group-B Bivalent NVX CoV2373 + NVX CoV2601. The registry reports zero deaths in both groups. Separately, it lists other adverse event counts of 10 among 190 and 4 among 210, respectively. These entries should be read using their stated categories and denominators.

The counts are descriptive and do not establish why an event occurred. A serious adverse event is not automatically caused by a study vaccine; the posted figures alone do not establish a causal relationship. The record does not provide an adjusted comparison, a confidence interval, or a statistical test for these counts. It also does not report enough detail to interpret the listed “other” category as equivalent to the primary solicited-event endpoint.

The serious-event term list includes suicidal ideation at 1.6%; adjustment disorder with anxiety, adjustment disorder with depressed mood, depression, post-traumatic stress disorder, and disruptive mood dysregulation disorder are each listed at 0.5%. These are registry entries, not conclusions about causality or comparative risk. The primary endpoint’s solicited local and systemic events during 7 days should be considered separately from these serious adverse event summaries.

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

This record describes a randomized, double-blinded Phase 3 comparison of a monovalent NVX-CoV2601 vaccine and a bivalent NVX CoV2373 + NVX-CoV2601 vaccine in adolescents previously vaccinated with mRNA COVID-19 vaccines. It identifies solicited local and systemic adverse events during 7 days following vaccination as the primary endpoint and lists immunogenicity outcomes as secondary outcomes.

The posted safety data provide descriptive counts for serious adverse events, other adverse events, and deaths in the two groups. They do not, by themselves, show whether differences between groups are more than could be expected from chance or other sources of variation. The registry record does not report a confidence interval or inferential comparison for these counts. It also does not provide a single overall result for the primary solicited-event endpoint in the information.

These data do not establish that an event was caused by vaccination, nor do they establish a comparative safety conclusion. They also do not answer the immunogenicity questions: although antibody outcomes are listed, their numerical results are not included in the record details.

In general, a clinical trial result is interpreted in light of its outcome definition, analysis population, statistical plan, follow-up, and uncertainty. Several of those details are not reported in the registry record. The study’s completed status and listed enrollment are not substitutes for those results or methods. The best-supported reading is therefore limited to the posted design and descriptive safety information, rather than a broader claim about effects, precision, or causation.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why outcome definitions matter. The primary endpoint is a solicited local and systemic adverse event measure during a defined period, whereas the safety summaries also include serious adverse events and other adverse event counts. Those are not interchangeable summaries. Keeping them separate prevents readers from treating one category as if it answered a different safety question.

The randomized, double-blinded, parallel-group design provides a framework for comparing the two vaccine formulations. In general, randomization can reduce confounding at assignment, and blinding can reduce biases linked to knowledge of group allocation. The registry record, however, does not include the procedural details or analysis outputs needed to evaluate how these design features were implemented and reflected in the results.

The record also illustrates the limits of descriptive event counts. Counts are useful for showing what was posted, but a comparative interpretation requires attention to uncertainty and the analysis method. No inferential comparison or confidence interval for the safety counts is reported. The multiple listed outcomes make access to a prespecified statistical plan particularly relevant, yet that plan and any multiplicity approach are not reported in the registry record.

Finally, the distinction between a trial’s design and a retrospective planning illustration is important. The sample-size section uses assumptions based on the observed effect and is not the trial’s own design justification or observed power. Treating it as such would overstate what the page establishes. Taken together, the record offers a useful case for reading trial registration details cautiously and separating posted observations from conclusions that depend on unreported methods.

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 information does not provide a single overall comparison for the primary endpoint of solicited local and systemic adverse events during 7 days. It therefore does not permit a complete interpretation of that endpoint from the posted material on this page. The serious adverse event counts should not be used as a replacement for it.

Important statistical details are not reported in the registry record: the analysis plan, the analysis populations, handling of missing data, any multiplicity strategy, and any interim analyses or stopping rules. The sample-size justification is also not reported. Without these details, readers cannot determine how the posted outcomes were selected for formal inference or how the analysis addressed incomplete information.

The adverse event summaries are descriptive in the information. No confidence intervals, hypothesis tests, or adjusted comparisons are reported for the counts. The listed serious-event terms and percentages do not establish causation, and the record does not provide the information needed to assess event attribution.

The registry lists immunogenicity outcomes, but their numerical results are not included in the registry record. Nor does the record detail the randomization procedure, the operational approach to blinding, or further participant eligibility characteristics. These limitations constrain interpretation of both the safety data and the broader study question; they should not be mistaken for evidence that an unreported method or result was absent from the study itself.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines — NCT05973006.
• Registry record last updated 2025-07-15; status last verified 2025-06.
• Results first posted 2025-07-15.
• 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

NCT05973006 is a completed Phase 3, randomized, double-blinded, parallel-group study sponsored by Novavax. It evaluates a monovalent NVX-CoV2601 formulation and a bivalent NVX CoV2373 + NVX-CoV2601 formulation in adolescents previously vaccinated with mRNA COVID-19 vaccines. The registry lists enrollment of 400, a study start date of 2023-08-16, and a primary completion date of 2024-04-01.

The primary outcome is participants with solicited local and systemic adverse events for 7 days following vaccination. The registry also lists antibody and IgG immunogenicity outcomes. Posted safety figures include serious adverse events, other adverse event counts, and deaths by group, but the record does not provide a single inferential comparison for the primary endpoint. The statistical analysis plan, missing-data approach, and multiplicity strategy are not reported in the registry record.