Evaluating the Safety and Immunogenicity of ALVAC-HIV and MF59®- or AS01B-adjuvanted Bivalent Subtype C gp120 in Healthy, HIV-uninfected Adult Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating the Safety and Immunogenicity of ALVAC-HIV and MF59®- or AS01B-adjuvanted Bivalent Subtype C gp120 in Healthy, HIV-uninfected Adult Participants (NCT03122223), a randomized phase 1, phase 2 study. The primary outcome is Number of Participants Reporting Local Reactogenicity Signs and Symptoms During the Vaccine Regimen.

2. Clinical Question

The trial title and summary frame the broader study around safety and immunogenicity. The primary outcome is specifically a count of participants reporting local signs and symptoms, with the maximum grade observed for each symptom presented. This endpoint therefore addresses reported local reactions during the vaccination regimen; it is not itself an assessment of immune response or protection against HIV.

The registry lists secondary outcomes concerning CD4+ T Cell responses and HIV-specific antibody responses, including binding antibody measures. These outcomes broaden the stated research questions beyond local reactogenicity. The record does not contain posted analyses for those outcomes, and it does not specify a single treatment contrast as the primary comparison. The central statistical question is consequently defined by the registered endpoint and follow-up window, while comparative estimates and their precision are not reported in the registry record.

3. Trial Design

This is a randomized, quadruple-masked, parallel-group phase 1/2a clinical trial. The registry describes an enrollment of 160 participants and marks the study as completed. The sponsor is the National Institute of Allergy and Infectious Diseases (NIAID). The record lists a start date of 2018-01-16 and primary completion on 2020-07-30.

Four arms are described: ALVAC-HIV with 100mcg Protein/MF59 and placebo; ALVAC-HIV with 100mcg Protein/AS01(B) and placebo; ALVAC-HIV with 20mcg Protein/AS01(B) and placebo; and placebo. The arm descriptions state that 50 participants will receive each of the three vaccine regimens and 10 will receive placebo. Those are the arm-description figures; the record does not provide a separate account of actual analyzed participants by arm.

Across the vaccine arms, ALVAC-HIV is described as a 1 mL injection in the left deltoid on Months 0, 1, 3, and 6. Protein and placebo injections are described for Months 3 and 6. The placebo arm receives placebo injections on the same listed schedule. These descriptions identify the planned interventions and administration schedule, but the registry record does not report adherence, deviations, or actual exposure by participant.

Randomization and masking are recorded, but the method used to generate the allocation sequence, conceal allocation, or implement masking is not reported in the registry record. The record also does not state the statistical design rationale or explain the unequal arm sizes described for the placebo group. The design can therefore be characterized from its listed groups and masking labels, but details beyond those entries should not be inferred.

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 Number of Participants Reporting Local Reactogenicity Signs and Symptoms During the Vaccine Regimen, measured over Measured through 7 days after participants' last vaccination at Month 0,1,3, and 6.

The primary endpoint is the number of participants reporting local reactogenicity signs and symptoms during the vaccine regimen. The registry specifies that these are measured through 7 days after participants' last vaccination at Month 0,1,3, and 6. Each symptom is graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017. The maximum grade observed for each symptom over the stated time frame is presented.

A participant count is a way to describe how many people experienced the endpoint, rather than how many separate symptom episodes occurred. This makes the outcome a participant-level summary, though its interpretation depends on how symptoms and grades are tabulated. The record does not provide the symptom-specific categories or the results for those categories. It also does not report a single combined estimate or a direct comparison between arms.

Local reactogenicity is used as a safety-related outcome because the trial is evaluating signs and symptoms temporally associated with the vaccination regimen. A grading framework adds information about severity as well as occurrence. General statistical interpretation: counts can describe the observed number of participants, while comparisons between groups require a clearly defined contrast and information about uncertainty. Neither comparative estimates nor confidence intervals for this primary outcome are reported in the registry record, so the endpoint's results cannot be interpreted as evidence for a difference between regimens.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies the primary outcome as a count of participants reporting local reactogenicity signs and symptoms. It does not post an analysis method or numerical result for this endpoint. The statistical concepts below explain how outcomes of this general kind can be understood; they are not a description of an analysis confirmed to have been used in the trial.

What does a participant count represent?

A count records how many participants meet an outcome definition. In this trial, the registered outcome is participant-based and concerns local signs and symptoms during a specified follow-up window. The description says the maximum grade for each symptom is presented. That means an interpretation needs to keep the symptom and grading structure in view: a count for one symptom or grade is not interchangeable with a count for another, and the registry's stated primary outcome contains several categories or time points rather than a single summary contrast.

Counts are often accompanied by the number of participants assessed, so readers can understand the denominator as well as the numerator. For comparisons between groups, the analysis also needs to specify which groups are being contrasted, how the endpoint is defined, and which participants are included. Here, the adverse-event entries provide at-risk and affected counts for selected categories, but the record does not post the primary local-reactogenicity results or an analysis population for that endpoint.

Why do comparative estimates need uncertainty?

A difference between observed counts can arise from a real underlying group difference or from sampling variability. General statistical explanation: a confidence interval expresses uncertainty around an estimate under the assumptions of the chosen method. A narrow interval indicates greater precision than a wide interval, while an interval that includes values representing no difference may be compatible with a range of interpretations. The interval does not correct for a poorly defined endpoint or missing data, and it does not establish clinical importance on its own.

No confidence intervals or comparative estimates for the primary endpoint are reported in the registry record. Therefore, the posted information does not allow a reader to judge the precision of a vaccine-versus-placebo contrast for local reactogenicity. The record also does not state whether the primary analyses would compare each vaccine regimen with placebo, compare vaccine formulations with each other, or use another contrast.

What does masking contribute?

The trial is labeled randomized and quadruple-masked, with a parallel model. In general, random assignment is intended to reduce systematic differences between groups at entry, while masking can reduce the influence of treatment knowledge on participant reporting, clinical assessment, or other study processes. These are design aims, not guarantees. The registry record does not report the allocation-generation procedure, concealment details, or which roles are included in the quadruple-masking label. It also does not report whether masking was maintained.

The parallel-group structure means participants are assigned to a group whose regimen is followed over the study schedule, rather than the registry describing a crossover sequence. The record lists four arms and their intervention schedules. The actual statistical comparison still depends on the analysis plan, which is not reported in the registry record.

How should the planning illustrations be read?

The planning assumptions state a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is described as a fraction of the observed effect. General statistical explanation: a significance level is a decision threshold used in a testing framework; a two-sided approach allows evidence in either direction. Equal allocation is an assumption about how participants are distributed between the two groups in an illustration. A normal approximation uses a mathematical distribution to approximate the sampling behavior of an estimate.

The sample-size calculations are explicitly planning illustrations based on the observed effect, not the trial's own design justification and not observed power. For non-time-to-event outcomes, the stated convention is participants per arm; for time-to-event outcomes, the convention is the total number of events. Since the primary outcome is not reduced to one comparison and the record does not provide primary analysis results, these planning assumptions should not be treated as a substitute for a reported trial analysis. No specific planning value should be attributed to the trial unless it is separately displayed with its assumptions and target contrast.

What can over-dispersion mean for counts?

General statistical explanation: some count outcomes vary more across participants or groups than a simple model assumes. This is called over-dispersion. If present, it can make standard errors from an overly restrictive model too small, giving an impression of greater precision than warranted. A suitable analysis may need to account for the extra variability. That issue is a general consideration for count data; the registry record does not report a dispersion parameter, identify an over-dispersion assessment, or specify a count-model analysis for this trial.

Because the posted primary outcome is a participant count with symptom categories and time points, it should not automatically be treated as a single unrestricted count outcome. The endpoint definition, symptom-specific summaries, denominators, and comparison plan all matter. The registry record does not report these analytic details. Consequently, general methods can explain what information a complete analysis would ordinarily need, but they cannot establish which method was used.

10. Multiplicity, Missing Data and Analysis Populations

The registered primary outcome covers several local symptoms or time points, and the registry description presents the maximum grade observed for each symptom. The record does not report a single comparison or explain how conclusions across symptoms, grades, arms, or time points would be handled. When many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. General statistical practice may address this through a prespecified hierarchy, adjusted testing, or a clearly exploratory interpretation. Which approach, if any, was planned for this trial is not reported in the registry record.

The record lists 21 outcome measures and no analyses. Secondary outcomes include cellular immune measures and multiple antibody response measures, with some specified assessment times. Their presence creates multiple potential questions, but the registry record does not state which are confirmatory, how multiplicity was addressed, or whether a testing hierarchy was defined.

Missing-data handling is not reported in the registry record. The record does not describe the number of participants with evaluable primary outcome data, how missed visits or incomplete symptom records were treated, or whether any imputation was used. Analysis populations, such as an intention-to-treat or per-protocol population, are also not reported. Without these details, the reported arm descriptions cannot establish who contributed to any particular outcome analysis.

The planned sample-size rationale and interim-analysis procedures are not reported in the registry record. The planning assumptions described for illustrations should not be mistaken for the original protocol's statistical plan. These gaps limit assessment of the analysis strategy, but they do not establish that a particular method was or was not used outside the registry record.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry's serious-event entries list 0 affected participants among 50 at risk in each of the three vaccine groups, and 0 among 10 at risk in the placebo group. Deaths are listed as 0 in all four groups. These are counts recorded in the registry, not estimates accompanied by confidence intervals or a formal comparison.

The other adverse-event entries list 32 of 50 participants for Vaccine w/ MF59, 28 of 50 for Vaccine w/ AS01B - High Dose, 26 of 50 for Vaccine w/ AS01B - Low Dose, and 6 of 10 for Placebo. The registry information does not provide event terms or definitions for these group-level counts in the adverse-event listing. They should therefore be read as recorded counts, not as evidence that particular types or severities of events occurred.

A zero recorded count does not show that the underlying risk is exactly zero, and it does not establish equivalence between groups. Interpretation also depends on the event definition, observation period, and completeness of follow-up, details that are not fully reported in the registry record. The serious-event fields should be kept distinct from the primary endpoint of local reactogenicity, for which the registry does not post results.

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

The registry record shows that a randomized, quadruple-masked phase 1/2a study was designed to evaluate safety and immunogenicity in healthy, HIV-uninfected adults. It documents three ALVAC-HIV and protein vaccine regimens, a placebo arm, a primary local-reactogenicity outcome, and secondary immune-response outcomes. It also records selected adverse-event counts and zero deaths in each group.

Those entries do not establish the comparative effect of one regimen versus another. The primary outcome is described across multiple symptoms or time points, and the registry notes that it was not reduced to a single comparison. No analysis results are posted for that endpoint. Without estimates and measures of uncertainty, the record cannot quantify the comparative frequency of local symptoms or establish how precisely any group difference was measured.

The same caution applies to immunogenicity. The listed CD4+ T Cell and antibody outcomes identify what the study intended to assess, but the registry record does not report their results. The posted safety counts cannot answer those immune-response questions. Conversely, an immune-response result, if available elsewhere, would not replace a safety analysis.

General statistical interpretation: an observed count is descriptive, while a claim about a group difference needs a defined contrast, suitable analysis, and uncertainty assessment. A lack of posted comparative analysis is not evidence of no difference. Likewise, zero recorded serious events in the registry is not proof that the underlying risk is zero or that the arms are equivalent.

The record therefore supports a description of the design and the scope of the registered questions, but it does not support a conclusion about whether any vaccine regimen had more or fewer local reactions, serious events, or immune responses than another. The sample-size illustrations, where presented, are planning scenarios rather than observed power or trial findings. Any interpretation should remain limited to what the registry actually reports.

13. Why This Trial Matters Statistically

This trial is statistically notable because it combines a multi-arm design with a primary outcome that is not a single scalar comparison in the registry description. The three active regimens differ in adjuvant and protein dose, and the placebo group is smaller in the arm descriptions. That structure raises practical questions about which comparisons are central and how results across arms and symptom categories should be interpreted.

The endpoint also illustrates the distinction between a participant-level count and a full comparative analysis. Reporting how many participants experienced symptoms can be useful, but a reader also needs outcome definitions, denominators, a prespecified contrast, and uncertainty estimates to evaluate differences. The registry record does not provide the primary analysis results or the comparisons used.

The trial's broader aim includes immunogenicity, with registered outcomes spanning cellular and antibody responses. Those measures can have different scales and interpretations from symptom counts. Treating them as a single family of interchangeable outcomes would obscure what each measure captures. The record identifies the outcome domains but does not post analyses that would permit an assessment of their comparative findings.

Finally, the posted serious-event counts and deaths are descriptive entries, not a complete inferential safety comparison. This distinction matters in registry reading: design details and event counts can be informative even when a result is not posted, but they cannot substitute for an analysis with defined populations and uncertainty. The record is therefore useful for identifying the trial's statistical questions and the limits of the available results.

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 results is that the registry record lists no analyses and does not post results for the primary local-reactogenicity endpoint. The endpoint involves multiple symptoms or time points, and the record does not identify a single comparison. This prevents a direct interpretation of comparative estimates or their precision.

The record lists secondary cellular and antibody outcomes but does not report their analysis results. It also does not report an analysis population, outcome-specific denominators, missing-data procedures, or participant flow through follow-up. The arm descriptions state the planned group sizes, but the registry does not separately report the number analyzed for each endpoint.

Several design and analysis details are not reported in the registry record, including the randomization procedure, allocation concealment, masking implementation, protocol sample-size justification, interim analyses, and statistical plan. The stated sample-size assumptions apply to planning illustrations and should not be used to infer the trial's original design rationale or observed power.

The safety listing provides group-level serious-event and other adverse-event counts, but the record does not give event terms or a comparative analysis in those entries. Zero recorded serious events and deaths are descriptive and do not establish a zero underlying risk. These limitations concern what can be concluded from the registry record; they do not determine what may be available in other study documents.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluating the Safety and Immunogenicity of ALVAC-HIV and MF59®- or AS01B-adjuvanted Bivalent Subtype C gp120 in Healthy, HIV-uninfected Adult Participants — NCT03122223.
• Registry record last updated 2023-03-14; status last verified 2023-03.
• Results first posted 2021-01-08.
• 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 identifies NCT03122223 as a completed, randomized, quadruple-masked, parallel phase 1/2a trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), with enrollment of 160. It evaluates ALVAC-HIV with bivalent subtype C gp120 protein using MF59 or AS01(B) adjuvant in healthy, HIV-uninfected adults, alongside a placebo arm.

The primary outcome is the number of participants reporting local reactogenicity signs and symptoms during the vaccine regimen, graded using the DAIDS severity table and observed through 7 days after the last vaccination. The registry lists 21 outcome measures and zero analyses. It posts selected adverse-event counts, including zero serious events and zero deaths in each group, but does not post the primary outcome analysis or secondary immunogenicity results.

The record describes the trial's design and registered questions, but comparative estimates, uncertainty measures, analysis populations, and important statistical-plan details are not reported in the registry record.