This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Trial to Model Primary, Secondary, and Tertiary Dengue Using a Monovalent Vaccine (NCT05691530), a non-randomized phase 1 study. The primary outcome is Number of Participants With Local Adverse Events (AEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05691530 |
| Phase | Phase 1 |
| Condition | Response To Dengue Exposure |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 127 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institutes of Health Clinical Center (CC) |
| Results posted | Yes |
2. Clinical Question
Population
Healthy people aged 18 to 59 years, classified according to their dengue or flavivirus antibody profiles.
Intervention
The monovalent vaccine candidate rDEN3Δ30/31-7164, administered by injection into the fat under the skin of the upper left arm.
Comparator
Participant groups with different antibody profiles: flavivirus-naive, polytypic dengue virus antibody profile, and primary heterotypic dengue virus antibody profile. These are not randomized treatment and control groups.
Primary question
How many participants in the per protocol subset had at least one solicited local adverse event through day 28 after vaccination?
The trial title frames the study as an effort to model primary, secondary, and tertiary dengue using a monovalent vaccine. Its stated objectives were to test a potential dengue vaccine and to examine whether side effects and immune responses differed according to previous dengue exposure. The registry record describes three antibody-profile groups, but the available group descriptions are incomplete. Details sufficient to reconstruct all profile rules are not reported in the registry record.
The primary endpoint concerns local reactions at the injection site, including pain, tenderness, bruising, redness or erythema, swelling or induration, and itching. The endpoint is a participant count: a participant is counted if at least one solicited local event occurred in the specified period. It is not a measure of the number of separate reactions or their severity. The registry record does not report a primary-endpoint result breakdown in the registry record for this analysis, so the specified question should not be mistaken for a reported estimate of local-event frequency.
3. Trial Design
This was a phase 1, non-randomized, parallel trial of rDEN3Δ30/31-7164. The registry record lists quadruple masking, but does not identify which roles were masked or describe how masking was maintained. The planned enrollment was 127 participants. The study is marked completed, with a start date of 2023-03-07 and a primary completion date of 2025-04-23.
Participants were classified by day 0 dengue antibody profile into flavivirus-naive, polytypic dengue virus antibody profile, or primary heterotypic dengue virus antibody profile groups. The description indicates that antibody testing and, for some categories, vaccination and travel history informed classification. The complete classification rules are not reported in the registry record. Since assignment was not randomized, the groups are not interchangeable by design. They represent different pre-existing profiles rather than allocated doses or a vaccine-versus-placebo comparison.
The brief summary describes screening with physical examination, urine and blood tests, and a travel-history survey. It also describes vaccination and repeated clinic visits with blood draws over a period extending to 7 months. Lymph node aspiration was optional. These are descriptions of the trial procedures; the available record does not establish how many participants completed each procedure or visit.
The primary endpoint was assessed through day 28 after vaccine administration in the per protocol subset, defined according to the participant assignment determined by the day 0 dengue antibody profile. The registry lists secondary outcomes concerning neutralizing antibody titers, fold-change in titers, and dengue-specific CD8+ T-cells. Their detailed result estimates and analysis methods are not reported in the registry record. There is no randomized control group in the design, so observed differences between profile groups cannot be interpreted as randomized comparisons.
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: 127 participants consented to this study: * 45 participants started the study intervention * 69 were screen failures * 13 were eligible but not randomized (back up)
Overall Study
| Stage | Flavivirus naïve | Polytypic Dengue Virus Antibody Profile | Primary Heterotypic Dengue Virus Antibody Profile |
|---|---|---|---|
| STARTED | 14 | 13 | 18 |
| COMPLETED | 14 | 13 | 18 |
| NOT COMPLETED | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The 'per protocol subset', which is based on participants assignment determined by day 0 dengue antibody profile.
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.
| Characteristic | Unit | Flavivirus naïve | Polytypic Dengue Virus Antibody Profile | Primary Heterotypic Dengue Virus Antibody Profile | Total |
|---|---|---|---|---|---|
| Participants analysed | 14 | 13 | 18 | 45 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 14 | 13 | 18 | 45 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 7 | 6 | 15 | 28 |
| Sex: Female, Male: Male | Participants | 7 | 7 | 3 | 17 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 4 | 3 | 5 | 12 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 10 | 10 | 13 | 33 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 5 | 4 | 11 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 0 | 2 |
| Race (NIH/OMB): White | Participants | 8 | 4 | 11 | 23 |
| Race (NIH/OMB): More than one race | Participants | 1 | 1 | 1 | 3 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 | 2 | 2 | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Local Adverse Events (AEs), measured over Through day 28 after vaccine administration.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with at least one solicited local adverse event through day 28 after vaccine administration. The listed local reactions are injection site pain, tenderness, bruising, redness or erythema, swelling or induration, and pruritus. Events were to be captured through investigator examination and participant history. The endpoint population is the per protocol subset, classified using day 0 dengue antibody profile.
This endpoint is useful for describing the proportion of participants who experienced any specified local reaction during a defined period after vaccination. Counting participants rather than individual event episodes avoids counting one person repeatedly for multiple local symptoms, but it also compresses information: one mild reaction and several reactions in the same participant both contribute one participant to the count. The endpoint does not, by itself, communicate severity, duration, or the number of reactions.
The registry record identifies the endpoint and its timeframe but does not report the primary-endpoint counts or a group-specific estimate in the registry record for this analysis. The other adverse-event fields cannot be assumed to be the primary local endpoint, because their definitions and relationship to the solicited local-event measure are not specified. Consequently, the endpoint definition can be interpreted, but its observed frequency and precision cannot be described from these registry entries.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a non-randomized study in which participants were grouped by dengue or flavivirus antibody profile. That design matters for interpretation: differences between groups could reflect their pre-existing profiles or other differences between participants, as well as any differences in observed responses after vaccination. The group comparisons therefore do not have the protection against confounding that random allocation can provide. The registry entries do not establish which characteristics differed across groups.
The primary question concerns participants with at least one solicited local adverse event through day 28. However, primary-endpoint result counts, estimates, and confidence intervals are not reported in the registry record available for this analysis. It is therefore not possible to describe the primary endpoint’s observed frequency or to assess the precision of a group comparison. The definition of an endpoint is not itself evidence about its result.
Separate safety fields report serious adverse event counts of 1 among 14 at risk in the flavivirus-naive group, 0 among 13 at risk in the polytypic dengue virus antibody profile group, and 0 among 18 at risk in the primary heterotypic dengue virus antibody profile group. These are sparse counts. With few observed events, estimates of group differences would be imprecise, and a zero count does not establish that the underlying risk is zero. The registry also lists Skin infection at 7.1% among the serious adverse event terms; the registry entries do not identify the group associated with that term or explain its relationship to the group counts.
The fields for other adverse events report affected counts of 14 among 14 at risk, 13 among 13 at risk, and 18 among 18 at risk, respectively. These counts are distinct from the serious-event counts and should not be treated as the primary solicited local endpoint without a definition establishing that connection. They also do not reveal how many events each participant had, how severe they were, or whether they were considered related to vaccination.
Immune-response outcomes are listed, but their numerical results are not reported in the registry record available for this analysis. No effect estimates, uncertainty intervals, or hypothesis-test results for those outcomes are included in the registry record. The posted information therefore supports a cautious account of study design and the listed safety counts, not a conclusion about comparative immune responses or the size and precision of the primary local-event result.
9. Statistical Methods Explained
The record identifies a participant-count endpoint: whether a participant experienced at least one specified local adverse event in the period through day 28. This is a binary outcome at the participant level. For a group, the observed event count is interpreted relative to the number of participants at risk or assessed for that outcome. A count without its relevant denominator can be difficult to interpret, while a count with a denominator still does not show the range of possible underlying event rates.
What does a confidence interval communicate?
General statistical explanation: A confidence interval expresses uncertainty around an estimate under a stated statistical procedure. A relatively wide interval indicates that the data are compatible with a broader range of values; a narrow interval indicates greater precision under that procedure. Intervals are especially important when event counts are small, because a single observed event can have a substantial influence on an estimate. The registry entries do not report confidence intervals for the primary endpoint or the serious adverse event counts.
Why does the non-randomized design matter?
General statistical explanation: Random assignment tends to balance measured and unmeasured characteristics between treatment groups on average. In a non-randomized comparison, group membership can be connected to characteristics that also relate to outcomes. Here, the groups are defined by antibody profiles rather than randomized allocation. A difference in observed outcomes between those groups would therefore be descriptive and would not, on its own, isolate an effect caused by the vaccine or by antibody profile. Adjustment can sometimes address measured differences, but it cannot automatically remove unmeasured confounding. Whether adjusted analyses were planned or performed is not reported in the registry record.
The record lists quadruple masking, which can reduce the influence of expectations on assessment or reporting in some settings. The specific people masked, the procedures used, and whether masking was successful are not reported in the registry record. Masking does not change the non-randomized basis for the profile groups and does not itself remove confounding.
What can be learned from sparse counts?
General statistical explanation: When events are uncommon, estimates based on counts can be unstable. A group with no observed events can still have a nonzero underlying event probability; the sample may simply not have captured an event. Conversely, one event in a small group does not establish a stable estimate of risk. Confidence intervals and transparent denominators help show this uncertainty, but do not eliminate it. The serious-event counts in the registry are small, and no corresponding uncertainty intervals are reported in the registry record.
The endpoint counts participants with at least one local event rather than the total number of event episodes. This distinction matters: repeated symptoms in one participant do not increase the participant count beyond one. A count of affected participants therefore does not describe event burden, duration, or severity. The event definition and the collection method—investigator examination and participant history—give useful context, but detailed severity and duration results are not reported in the registry record.
How should planning calculations be read?
General statistical explanation: Sample-size calculations describe a hypothetical future design under specified assumptions; they are not a measure of the trial’s observed power. The planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Those assumptions do not describe the actual non-randomized allocation into antibody-profile groups. Any planning counts should be read as hypothetical design illustrations, not as observed results or proof that the study had adequate power. The planning illustration is not the trial’s own design justification, and a design justification is not reported in the registry record.
For a binary participant endpoint, the number needed for a future study depends on the assumed event frequency, the contrast to be detected, the chosen error rates, and the analysis approach. If the observed effect used as a planning reference is uncertain, a planning result built from it inherits that uncertainty. The registry entries do not report a protocol rationale, a prespecified minimum important difference, or the assumptions used by the trial investigators for their own sample-size planning.
There are no analysis entries reported in the registry record, and no statistical test or model for the primary endpoint is described. It is not possible to attribute a particular estimator, adjustment method, or missing-data approach to the investigators. Any general statistical description should therefore be kept separate from claims about the analysis actually used in this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 outcome measures and secondary outcomes covering antibody titers, fold-change in neutralizing antibody titers, and dengue-specific CD8+ T-cells. When a study examines multiple outcomes or multiple comparisons, the chance of obtaining at least one apparently notable result by chance can increase. General statistical explanation: Multiplicity procedures can control that risk, but they require a prespecified strategy, such as identifying a primary comparison or adjusting inference across a defined family of tests. The multiplicity strategy for this trial is not reported in the registry record.
The record identifies a primary endpoint and a per protocol subset, but the analysis population definitions beyond that description are not reported in the registry record. The number of participants with missing endpoint data, the reasons for missingness, and any rules for handling missing observations are also not reported. Missingness can affect interpretation if the likelihood of having an observed result is related to participant characteristics or outcomes. Whether that occurred in this trial cannot be assessed from the available information.
Interim analyses, stopping rules, and any planned adjustments to significance levels are not reported in the registry record. Nor are the analysis methods for the listed secondary outcomes. Without these details, the record does not support a complete assessment of how multiplicity, incomplete data, or analysis-population choices were handled. These omissions do not establish that the trial lacked such procedures; they mean the procedures are not documented in the registry entries.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Flavivirus naïve | 1 | 14 | 7.1% |
| Polytypic Dengue Virus Antibody Profile | 0 | 13 | 0.0% |
| Primary Heterotypic Dengue Virus Antibody Profile | 0 | 18 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Flavivirus naïve | 0 of 14 |
| Polytypic Dengue Virus Antibody Profile | 0 of 13 |
| Primary Heterotypic Dengue Virus Antibody Profile | 0 of 18 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Flavivirus naïve | 14 of 14 |
| Polytypic Dengue Virus Antibody Profile | 13 of 13 |
| Primary Heterotypic Dengue Virus Antibody Profile | 18 of 18 |
Most frequent serious adverse event terms
| Event term | Organ system | Flavivirus naïve | Polytypic Dengue Virus Antibody Profile | Primary Heterotypic Dengue Virus Antibody Profile |
|---|---|---|---|---|
| Skin infection | Infections and infestations | 1 of 14 | 0 of 13 | 0 of 18 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Flavivirus naïve | Polytypic Dengue Virus Antibody Profile | Primary Heterotypic Dengue Virus Antibody Profile |
|---|---|---|---|---|
| Fatigue | General disorders | 8 of 14 | 6 of 13 | 9 of 18 |
| Hyperglycaemia | Metabolism and nutrition disorders | 9 of 14 | 7 of 13 | 7 of 18 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 11 of 14 | 3 of 13 | 8 of 18 |
| Anaemia | Blood and lymphatic system disorders | 4 of 14 | 6 of 13 | 10 of 18 |
| Procedural pain | Injury, poisoning and procedural complications | 7 of 14 | 5 of 13 | 7 of 18 |
| Headache | Nervous system disorders | 8 of 14 | 4 of 13 | 6 of 18 |
| Neutropenia | Blood and lymphatic system disorders | 3 of 14 | 4 of 13 | 8 of 18 |
| Leukopenia | Blood and lymphatic system disorders | 3 of 14 | 4 of 13 | 7 of 18 |
| Myalgia | Musculoskeletal and connective tissue disorders | 3 of 14 | 2 of 13 | 7 of 18 |
| Hypokalaemia | Metabolism and nutrition disorders | 5 of 14 | 4 of 13 | 2 of 18 |
Serious events with the highest arm-level rate: skin infection (7.1%).
The serious adverse event fields report 1 affected participant among 14 at risk in the flavivirus-naive group, 0 among 13 at risk in the polytypic dengue virus antibody profile group, and 0 among 18 at risk in the primary heterotypic dengue virus antibody profile group. These are counts within the listed groups, not randomized comparisons. The small counts, including zero counts, do not establish that serious events are absent in the underlying population or that one profile group has a different risk from another.
The record lists Skin infection at 7.1% among the top serious adverse event terms. The registry entries do not specify which group this term belongs to, how the percentage was calculated, or whether the event was considered related to vaccination. It should not be assigned to a particular group or interpreted as a causal finding from the information available.
The separate other-adverse-event fields show affected counts of 14 among 14 at risk, 13 among 13 at risk, and 18 among 18 at risk across the listed profile groups. Those fields are not interchangeable with serious adverse events or with the primary endpoint of solicited local reactions. The record details do not provide severity, duration, individual event histories, or causal attribution for those other events.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a completed phase 1, non-randomized study of a monovalent dengue vaccine candidate, with participants categorized by antibody profile. It specifies a primary endpoint focused on solicited local adverse events through day 28 and lists immune-response outcomes. It also reports sparse serious adverse event counts for the profile groups. These details describe the study question and some safety information; they do not amount to a randomized assessment of treatment effects.
The primary local-event endpoint’s observed counts and estimates are not reported in the registry record available for this analysis. Consequently, the frequency of those events and the precision of any comparison cannot be determined from the endpoint definition. The listed serious-event counts likewise do not establish equivalence among profile groups. In general, an absence of observed events in a group is not proof that the underlying event risk is zero, particularly when counts are sparse.
The non-randomized grouping also limits causal interpretation. Participants entered profile categories according to their antibody status, rather than being allocated at random to those categories. Any observed differences could be associated with prior exposure or other group characteristics. The registry entries do not report an adjusted analysis that would clarify the role of measured differences, and statistical adjustment would not necessarily resolve unmeasured confounding.
The record lists immune-response outcomes but does not include their numerical results in the registry entries. It therefore does not support conclusions about the direction, magnitude, or precision of those responses. More broadly, a phase 1 study’s design and reported outcomes should be interpreted within the measures and populations it specifies; they do not, by themselves, establish how results apply beyond the participants and assessments recorded. No medical recommendation follows from these statistical descriptions.
13. Why This Trial Matters Statistically
Statistically, this trial illustrates why the structure of a comparison is as important as the outcome count. The antibody-profile groups may be informative for describing responses among people with different prior dengue or flavivirus profiles, but they are not randomized groups. Their comparisons are therefore vulnerable to differences associated with the profiles themselves. A clear account of the allocation structure prevents descriptive contrasts from being mistaken for causal treatment effects.
The specified primary endpoint also shows why outcome definitions matter. Counting participants with at least one solicited local reaction through a fixed period answers a focused question about whether participants experienced a reaction. It does not describe how many reactions occurred, their severity, or how long they lasted. Keeping that endpoint separate from serious adverse events and other adverse-event counts is necessary for a sound reading of the results.
Precision matters particularly when event counts are sparse. The reported serious-event counts include zero values in two profile groups and one affected participant in another. Those counts are useful descriptive information, but they cannot establish that underlying risks are equal or absent. Uncertainty intervals and clear outcome-specific denominators would be important for judging the range of values compatible with the data; those intervals are not reported in the registry entries.
Finally, the registry lists immunologic outcomes alongside safety outcomes, but the numerical immune-response results and analysis details are not available in the registry record. Separating what is specified from what is numerically reported helps keep design descriptions, outcome definitions, and evidence about results from being conflated.
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 available record leaves important limits on interpretation. First, the primary endpoint is defined, but its observed counts and estimates are not reported in the registry record for this analysis. The serious and other adverse-event fields cannot be substituted for that endpoint without a documented definition connecting them. Therefore, the primary local-event question cannot be answered from these registry entries.
Second, the study is non-randomized, and the groups are based on antibody profiles. The comparisons cannot be treated as like-for-like randomized contrasts. The complete profile classification criteria are not available, and the group descriptions are truncated. The record also does not report the demographic or clinical characteristics needed to evaluate comparability across groups.
Third, the serious-event counts are sparse, and no confidence intervals or group-comparison estimates are reported. The listed Skin infection term is not linked to a particular group in the registry entries, and its causal relationship to vaccination is not stated. The other adverse-event fields do not provide detail on event severity, duration, or attribution.
Finally, the analysis plan, missing-data methods, multiplicity approach, and investigator sample-size justification are not reported in the registry record. The listed secondary outcomes have no numerical results in the registry record for this analysis. The enrollment figure does not establish how many participants contributed to each endpoint, and the registry entries do not describe completion of follow-up or the reasons for any missing results. These gaps limit assessment of both precision and potential bias.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Trial to Model Primary, Secondary, and Tertiary Dengue Using a Monovalent Vaccine — NCT05691530.
- Registry record last updated 2026-06-16; status last verified 2026-05.
- Results first posted 2026-04-28.
- 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.
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18. Record Summary
The registry record describes a completed phase 1, non-randomized, parallel trial of rDEN3Δ30/31-7164, with quadruple masking listed. Planned enrollment was 127. Participants were classified into flavivirus-naive, polytypic dengue virus antibody profile, and primary heterotypic dengue virus antibody profile groups. The primary endpoint was the number of participants with at least one solicited local adverse event through day 28, assessed in a per protocol subset based on day 0 antibody profile.
The available safety fields report serious adverse event counts of 1 among 14 at risk, 0 among 13 at risk, and 0 among 18 at risk across the three groups, and list Skin infection at 7.1% among serious adverse event terms. Primary local-event results, numerical immune-response results, uncertainty intervals, and detailed analysis methods are not reported in the registry entries available for this analysis. Because group assignment was not randomized, the profile groups do not constitute like-for-like control groups.