Safety and Immunogenicity of pDNA Vaccines Expressing HIV M Group p24^Gag Conserved Elements and/or p55^Gag, Administered With IL-12 pDNA: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of pDNA Vaccines Expressing HIV M Group p24^Gag Conserved Elements and/or p55^Gag, Administered With IL-12 pDNA (NCT03181789), a randomized phase 1 study. The primary outcome is Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness.

2. Clinical Question

This is a safety and immunogenicity study, not a trial of clinical outcomes in people with HIV. Its primary endpoint concerns local reactogenicity: pain and/or tenderness following vaccination or placebo administration. The registry also lists immune-response outcomes based on flow cytometry and binding-antibody assays.

The treatment descriptions distinguish two vaccine regimens and two placebo controls. The posted safety record lists the vaccine groups as Group 1 and Group 2 and the controls as Control 1 and Control 2. The registry does not report a primary-endpoint comparison with numerical results, nor does it report numerical immune-response results in the record summarized for this analysis. Consequently, the clinical question can be described from the protocol record, but the posted information does not establish the size or precision of any difference in pain or tenderness between a vaccine group and its control.

3. Trial Design

The registry describes a randomized, quadruple-masked, parallel-group Phase 1 trial. It lists an enrollment of 56 and a completed status. The recorded study dates are 2017-10-18 for study start and 2019-10-25 for primary completion. The sponsor is the National Institute of Allergy and Infectious Diseases (NIAID).

The treatment plan includes two vaccine regimens. In Group 1, participants were scheduled to receive p24CE1/2 pDNA and IL-12 pDNA at Day 0 and Month 1, followed by p24CE1/2 pDNA, p55^gag pDNA, and IL-12 pDNA at Months 3 and 6. In Group 2, participants were scheduled to receive p55^gag pDNA and IL-12 pDNA at Day 0 and Months 1, 3, and 6. The corresponding control descriptions specify placebo at Day 0 and Months 1, 3, and 6. Intramuscular injection with electroporation is described in the study summary.

Random allocation is intended to reduce systematic differences between treatment groups, while masking is intended to limit the influence of treatment knowledge on participant experience, care, or outcome assessment. Those are general design principles; the registry record does not identify which roles were masked or describe the allocation procedure. The record identifies a parallel model, meaning the treatment groups are separate rather than a crossover sequence. It does not report the number assigned to each randomized arm in the design description. The at-risk counts in the safety record are reported separately and should not be treated as a complete account of allocation or follow-up.

The primary completion date marks the registry’s recorded primary-completion milestone; it does not, by itself, establish when every analysis was conducted or posted. Detailed information on the sample-size justification, interim analyses, protocol deviations, and statistical analysis plan is 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 Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness, measured over Measured through Month 0, 1, 3, 6.

The primary endpoint is the number of participants reporting local reactogenicity signs and symptoms of pain and/or tenderness. It is recorded as a participant count and is assessed through Month 0, 1, 3, and 6. The endpoint description states that events are graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.

Local pain and tenderness are useful safety and tolerability measures because they capture reactions at or near the administration site. Recording participant counts can make the occurrence of these symptoms easier to interpret than a total number of symptom episodes, particularly when a participant may have repeated assessments. That is a general measurement rationale, not a claim about how repeated reports were handled in this trial.

The record’s primary endpoint title combines pain and/or tenderness, and the stated timeframe spans several visits. Its description is truncated in the registry record after noting that the maximum grade observed for each symptom is used. The precise rule for combining symptoms, visits, or grades into the reported endpoint is therefore not fully available. The registry record does not report the primary-endpoint counts by arm or a numerical treatment comparison. Without those results, the endpoint definition can be described, but the occurrence or comparative frequency of local symptoms cannot be quantified from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical concepts in this discussion are general unless explicitly tied to a registry fact. They explain how trial results are usually interpreted; they do not imply that a particular analysis was conducted in this study.

What does a participant count represent?

A participant count records how many people in a defined group meet an outcome rule. For a safety endpoint, that rule might identify participants who experienced a symptom or event during a specified observation period. A count is not the same as the number of episodes: repeated events in the same participant may be treated differently depending on the endpoint definition. The registry identifies the primary outcome as a count of participants reporting pain and/or tenderness and says that the maximum grade observed for each symptom is used. The remaining details of how symptoms and visits were combined are not reported in the registry record.

Counts are most informative when accompanied by a clear denominator, a defined follow-up period, and the rule used to decide whether each participant qualifies. The safety record includes at-risk counts for its event categories, but it does not give the primary pain-and-tenderness counts by group. The available safety summary should therefore be read as its own descriptive record, not as a substitute numerator or denominator for the primary endpoint.

How should a confidence interval be understood?

General explanation: a confidence interval describes uncertainty around an estimated quantity under a specified statistical procedure. A narrow interval indicates greater precision than a wide interval, while an interval spanning values compatible with different conclusions may leave the direction or size of an effect uncertain. An interval does not remove limitations in the study design, outcome measurement, or completeness of reporting.

The registry record does not report a confidence interval for the primary endpoint or the safety counts. No interval can therefore be interpreted for the main comparison from this record. The absence of an interval is not evidence that the estimate is precise or that an effect is absent; it means that the estimate and its uncertainty are not reported in the record.

Why are small groups hard to compare?

General explanation: when groups contain few participants, a change in the outcome status of a small number of people can materially alter the observed count. Estimates based on small groups are commonly less precise, and apparent differences may be highly sensitive to individual observations. Randomization helps address systematic differences in expectation, but it does not guarantee that observed group characteristics or outcomes will be balanced in a small trial.

The registry’s safety record lists 25 participants at risk in each vaccine group and 3 in each control group. Those are the reported at-risk counts for that record, not a statement of the randomized allocation for every analysis. They support a cautious reading of the descriptive safety counts, particularly in the control groups. The record does not provide uncertainty estimates or a formal comparison for these figures.

What is over-dispersion, and does it apply?

General explanation: over-dispersion arises when variation in count outcomes exceeds what a chosen statistical model expects. It can make model-based standard errors too small if the extra variation is ignored. Whether a count model is appropriate depends on the outcome structure, the distribution of observations, and the analysis plan. This trial’s primary endpoint is described as a participant count, but the registry record does not report a count-model analysis, an over-dispersion assessment, or model assumptions. No claim about over-dispersion in the trial’s data is warranted.

What does the sample-size planning language mean?

The registry’s planning description characterizes sample-size values as illustrations computed from an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. Such planning values are not observed power and do not show that the trial was adequately powered for its outcomes. The description also distinguishes participant-per-arm planning for non-time-to-event outcomes from a total-event calculation for time-to-event outcomes using the Schoenfeld approach.

No numerical planning values are included in the registry record summarized for this analysis, and the registry does not report the trial’s own sample-size justification. The planning assumptions should not be mistaken for a prespecified design calculation or for an analysis of the trial’s achieved power. They also do not resolve the absence of reported primary-endpoint estimates and uncertainty intervals.

What can be inferred from the listed outcomes?

Outcome titles describe what investigators planned to measure and when, not the observed findings. The secondary outcomes include T-cell response rates and magnitudes, MIMOSA response rates, epitope-mapping responses, and binding-antibody responses. The record lists 20 outcome measures and 0 analyses. That entry does not supply numerical findings for the listed immune outcomes. Without reported estimates, denominators, missing-data handling, and analysis details, their magnitude and precision cannot be evaluated.

For a treatment comparison to be interpreted statistically, readers generally need the outcome definition, group-specific estimates, a measure of uncertainty, and a clear account of the population analyzed. That is general guidance. For this trial, the registry record does not report those elements for the primary endpoint in the available outcome entry. The statistical conclusion must consequently remain limited to describing the design and the posted safety counts.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures, including several T-cell response outcomes, antibody outcomes, and safety outcomes. When a study evaluates many outcomes or comparisons, the chance of finding an apparently unusual result by chance can increase. General approaches to this issue include prespecifying a primary outcome, organizing outcomes into a testing hierarchy, or adjusting inferential procedures. Which approach is appropriate depends on the study objectives and analysis plan.

The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or a statistical analysis plan explaining how multiple outcomes or comparisons were handled. It lists 0 analyses. That registry entry does not establish that no analysis was performed; it indicates that analyses are not listed in the record. No correction or unadjusted testing strategy should be inferred.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not state how participants with incomplete visits, missing assay results, or unavailable endpoint assessments were handled, nor does it identify an intention-to-treat, per-protocol, or other analysis population for the outcomes discussed. These details matter because the number analyzed can differ from the number enrolled or at risk, and because missingness may affect the interpretation of group comparisons.

The safety record provides at-risk counts by listed group, but it does not describe missingness or explain whether those counts represent all participants randomized, treated, or assessed for each safety outcome. The primary endpoint’s numerical results and analysis denominator are not reported. Accordingly, neither the impact of missing data nor the handling of multiple comparisons can be evaluated from 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 safety record separates serious events from other events and reports both the number at risk and the number affected. In Group 1: Vaccine, 0 of 25 at risk were affected by serious events and 16 of 25 by other events. In Group 2: Vaccine, 0 of 25 were affected by serious events and 17 of 25 by other events. In Group 3: Control 1, the corresponding counts were 0 of 3 and 2 of 3. In Group 4: Control 2, they were 0 of 3 and 2 of 3. Deaths were recorded as 0 in each listed group.

These are descriptive counts over the registry’s safety reporting, not estimates of comparative treatment effects. A zero reported serious-event count means no affected participants were recorded in that category for the group in this entry; it does not establish that the risk is zero. The control groups have small at-risk counts, so their observed counts provide limited information about uncommon events. “Other events” should not be read as synonymous with the primary local pain-and-tenderness endpoint. The registry record does not provide a serious-event comparison, confidence interval, or detailed event-term listing for these groups.

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

The trial record describes a randomized, quadruple-masked, parallel-group Phase 1 study of two HIV pDNA vaccine regimens administered with IL-12 pDNA, with placebo control groups. It specifies a primary safety endpoint of participant-reported local pain and/or tenderness and lists immune-response outcomes. It also posts descriptive safety counts, including zero affected participants for serious events in each listed group and nonzero counts in the category of other events.

Those details do not establish the frequency of the primary endpoint because its group-specific numerical results are not reported in the registry record. They also do not establish the size or precision of an effect on T-cell or antibody responses, because numerical immune-response results are not reported. The study’s purpose and outcome list cannot be treated as evidence that an intended response occurred.

The zero serious-event counts are observations in the listed safety groups, not proof that serious events cannot occur or that the risk is absent. The reported at-risk counts, particularly the small counts in the control groups, limit how much can be inferred about uncommon outcomes. In addition, no confidence intervals or formal comparative analyses are included in the record for these safety figures.

More broadly, a Phase 1 trial’s design and reported outcomes address the questions measured in that study and population. The record does not report clinical outcomes in people with HIV, and it does not support conclusions beyond the described healthy, HIV-uninfected adult population. It also does not provide enough statistical detail to assess missing-data handling, multiplicity, or the exact analysis populations.

The most defensible reading is therefore descriptive: the registry documents the study design, planned vaccine schedules, endpoint definitions, and specific safety counts. It does not provide the numerical primary-endpoint or immune-response results needed to quantify those outcomes or their uncertainty. These limitations concern the available record and should not be converted into claims that an outcome did or did not occur outside what is explicitly recorded.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a well-described study question and a fully reported result. The record identifies randomization, masking, a parallel design, two vaccine regimens, placebo controls, and a primary safety endpoint. It also gives a defined grading reference and assessment timeframe for local pain and/or tenderness. Those details make the intended measurement question understandable.

At the same time, a statistical interpretation requires more than an outcome title. Group-specific results, analysis denominators, and measures of uncertainty are needed to assess how large an observed difference may be and how precisely it is estimated. Those primary-endpoint results are not reported in the registry record. This prevents readers from moving from the endpoint definition to a quantified comparison.

The posted safety counts also illustrate why denominators and study context matter. The record reports different at-risk counts for vaccine and control groups, including small control-group counts. Counts can be reported accurately while still providing limited precision for comparing groups or evaluating uncommon events. General statistical caution is especially important when a study is Phase 1 and has a safety and immunogenicity focus.

Finally, the registry lists many planned outcome measures but does not list analyses or describe a multiplicity strategy, missing-data method, or analysis population. That makes it difficult to assess how a complete set of outcomes was analyzed or how selective reporting was addressed. The statistical importance of this trial record lies both in its explicit design and in recognizing the limits created by incomplete outcome reporting. Separating what was planned, what is posted, and what can be inferred is essential to a sound reading.

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 does not report numerical results for the primary endpoint of local pain and/or tenderness. It therefore does not permit a direct estimate of how many participants met that endpoint in each arm or how groups compare. The endpoint description is truncated after stating that the maximum grade observed for each symptom is used, leaving the precise aggregation across symptoms and visits unclear.

The safety information is limited to group-level counts for serious events, other events, and deaths. The record does not provide event-level descriptions for the other-event category, comparative estimates, or uncertainty intervals. The smaller at-risk counts in the control groups constrain interpretation of observed counts, particularly for uncommon events. These safety data should not be substituted for the missing primary reactogenicity results.

Although the registry lists secondary immune-response outcomes, numerical findings for those outcomes are not reported in the record. The listed outcome definitions and assessment times do not reveal observed response rates or magnitudes. The record also does not report the analysis populations, handling of missing observations, multiplicity procedures, or the statistical methods used for these outcomes.

The registry describes the study as randomized and quadruple-masked but does not describe the allocation procedure or identify the roles covered by masking. It does not report a sample-size justification for the trial, interim analyses, or a detailed statistical analysis plan. The separate planning description is characterized as an illustration based on an observed effect and specified assumptions, not as the trial’s own design justification; no numerical planning result is included in this record summary.

These limitations concern what the registry record reports. They prevent a complete assessment of the primary endpoint and immune-response findings, but they do not establish that analyses or additional documentation do not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of pDNA Vaccines Expressing HIV M Group p24^Gag Conserved Elements and/or p55^Gag, Administered With IL-12 pDNA — NCT03181789.
• Registry record last updated 2024-02-07; status last verified 2024-01.
• Results first posted 2021-10-14.
• 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 NCT03181789 as a completed, randomized, quadruple-masked, parallel-group Phase 1 trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). It lists an enrollment of 56 and a population of healthy, HIV-uninfected adult participants. The study evaluated p24CE1/2 pDNA and p55^gag pDNA vaccine regimens administered with IL-12 pDNA, with placebo control groups and intramuscular delivery with electroporation described in the study summary.

The primary outcome is the number of participants reporting local pain and/or tenderness, assessed through Month 0, 1, 3, and 6 using the stated Division of AIDS grading reference. Numerical results for this endpoint and for the listed immune-response outcomes are not reported in the registry record. The safety entry reports 0 serious-event-affected participants in each listed group, along with counts for other events and deaths.

The record lists 20 outcome measures and 0 analyses. Detailed statistical methods, missing-data procedures, multiplicity handling, analysis populations, and a trial-specific sample-size justification are not reported in the registry record.