An Evaluation of Repeated Oral Doses of JNJ-64281802 Against DENV-3 Challenge: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Evaluation of Repeated Oral Doses of JNJ-64281802 Against DENV-3 Challenge (NCT05048875), a randomized phase 2 study. The primary outcome is Assess the Antiviral Activity of the Study Drug (JNJ 64281802) Versus Placebo in Terms of Reduction of Dengue Infection..

2. Clinical Question

The study’s brief summary states the hypothesis that the highest dose is superior to placebo with respect to antiviral activity in healthy adults inoculated with Dengue Serotype 3. The registry’s primary endpoint is a summary of viral RNA concentration over time, rather than a clinical outcome such as symptoms or disease complications. Lower values represent less viral-load exposure over the measurement period, but the endpoint alone does not establish effects on outcomes beyond the measured viral load.

The posted results contain estimates for several groups, including Cohort 1 dose groups and Cohort 2 daily and weekly dosing groups. They are not presented as one pooled treatment-versus-placebo result. The registry record does not report a single direct treatment contrast, confidence interval for that contrast, or p-value in the listed primary outcome results. This means the posted arm estimates can be described, but they do not by themselves answer every inferential question implied by the study hypothesis.

3. Trial Design

This is a Phase 2 randomized, placebo-controlled study of repeated oral doses of JNJ-64281802 in a dengue human challenge model. The registry lists the model as sequential and masking as triple; the official title describes the trial as doubleblind. These are the descriptions recorded in the registry, and the record does not explain the difference between the masking labels or specify which study roles were masked.

The study enrolled healthy adults who were inoculated with Dengue Serotype 3. The registry lists enrollment of 56 and a completed status. The recorded study start is 2022-02-03 and primary completion is 2023-05-16. The sponsor is the National Institute of Allergy and Infectious Diseases (NIAID).

Cohort 1 includes high-, medium-, and low-dose JNJ-64281802 groups and a placebo group. The high-dose description says participants were enrolled in a sentinel group before the remaining participants, with the same dosing regimen across the combined high-dose arm. The medium- and low-dose description says those groups were enrolled after completion of Group 1a. Placebo data for the two Cohort 1 groups are described as combined per the sponsor’s analysis. Exact dose amounts and dosing schedules for these Cohort 1 groups are not reported in the registry record.

The posted primary outcome results also include Cohort 2 placebo, daily-dose, and weekly-dose groups. The Cohort 2 group descriptions and how this cohort relates to the trial’s sequential design are not reported in the registry record. Therefore, the listed results span more groups than the brief summary’s highest-dose-versus-placebo hypothesis alone. The registry record does not provide enough detail to infer the rationale for the sequence, the allocation procedure, or how decisions to proceed between groups were made.

The primary outcome timeframe is Day1-29. The endpoint is the area under the DENV-3 RNA viral-load concentration-time curve, expressed as Log10 AUC VL (log10 copies/mL/28days). The record lists 32 outcome measures and 31 posted secondary outcomes. Secondary measures include safety assessments, vital signs, ECG intervals, laboratory assessments, and dengue infection-associated adverse events.

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.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: One subject in the High Dose Group (Cohort 1 Group 1) has a missing sample on Day 29 and is therefore excluded from this analysis since the missing value could not be imputed according to the SAP rules.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Group 1 Placebo and Group 2 Placebo are combined in one category to be consistent with how data was analyzed. Group 2 placebo were not analyzed on their own (group 1/2 placebos were combined during analysis).

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Assess the Antiviral Activity of the Study Drug (JNJ 64281802) Versus Placebo in Terms of Reduction of Dengue Infection., measured over Day1-29.

The primary endpoint summarizes DENV-3 RNA viral load from immediately before inoculation on Day 1 until Day 29. It is the area under the viral-load concentration-time curve, reported as a log10 AUC. An area-under-the-curve measure combines observations across the specified period, representing overall viral-load exposure rather than a measurement at one particular visit.

This type of endpoint is used to assess antiviral activity because it captures both the level and duration of measured viral load over the follow-up window. A lower AUC indicates a lower accumulated viral-load measure during that window. It is not, by itself, a direct measure of symptoms, complications, or longer-term outcomes.

The registry reports least-squares means and 90% confidence intervals for the listed groups. Its endpoint description specifies a Tobit analysis of variance model and says least-square differences are calculated versus placebo. The displayed arm results include estimates for Cohort 1 and Cohort 2 groups. The registry record does not report a direct contrast estimate or a p-value alongside these group-level values, so the arm estimates should not be mistaken for a complete set of treatment-versus-placebo comparisons.

The listed unit includes 28days, while the stated measurement window runs from Day 1 to Day 29. These are the registry’s endpoint labels; the record does not provide additional explanation of the unit wording.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary endpoint as the area under the DENV-3 RNA viral-load curve from immediately before inoculation on Day 1 to Day 29. The analysis variable is log10 AUC DENV-3 RNA D1-29, rounded to 2 decimal places. The listed summaries are least-squares means with 90% confidence intervals. Least-squares means are model-based estimates for each group, rather than simple arithmetic averages of the observed values. The record says the least-square differences are calculated versus placebo, but does not display those differences in the listed results.

What the Tobit model does

The primary outcome description specifies a Tobit analysis of variance model, with study drug as a fixed covariate and a normally distributed error term. A Tobit model is used when outcome values are censored at a boundary: the actual value is not observed below or above that boundary, but is known to fall beyond it. Here, values are left censored at 2.70 log10 copies/ml/days1-29. The record identifies 36 copies/ml as the assumed limit of detection and says values <LOD are imputed with 18 copies/ml.

In general, censoring matters because treating every below-detection observation as if it were an ordinary, precisely measured value can misrepresent the data. A model that accounts for censoring uses the information that a value lies below the limit rather than treating it as fully observed. The registry’s note also specifies an imputation value for below-detection observations; it does not explain further how that imputation is integrated with the model or provide sensitivity analyses. The error term’s normal-distribution assumption is a model assumption, not a statement that all individual viral-load measurements are normally distributed.

Reading the estimates and intervals

Each posted group value is an estimated mean on the endpoint scale, with a 90% confidence interval. A confidence interval expresses uncertainty in an estimate under the chosen model and assumptions. It is not a range for individual participants and it does not directly answer whether two groups differ. To assess a treatment-placebo contrast, readers need the estimated difference and its uncertainty. Although the endpoint description says differences are calculated versus placebo, the registry results do not show the contrast estimates or their p-values. Those details are not reported in the registry record.

The analysis groups are small, and the confidence intervals communicate that estimates are uncertain. The point estimates should therefore not be treated as exact values or as a ranking that proves one regimen is better. General statistical principle: a comparison should be interpreted using the contrast and its interval or test, not by comparing separate group intervals as if they were a formal test. The registry’s 90% intervals are for the posted group estimates; the record does not state that they are simultaneous intervals adjusted for multiple comparisons.

Sequential and multiple-group context

The registry labels the model as sequential and lists several dose groups across two cohorts in the posted results. In general, sequential designs can involve decisions or enrollment stages as a study proceeds. The record describes sentinel enrollment in Cohort 1 and says the other Cohort 1 groups followed completion of Group 1a. However, the decision rules, any interim analyses, and the statistical plan for sequencing are not reported in the registry record. It would be inappropriate to infer that interim hypothesis testing occurred or to assume a particular error-control method.

There are multiple dose groups and many outcomes, including 31 posted secondary outcomes. In general, examining several comparisons can increase the chance of finding a nominally unusual result if no adjustment is made. Whether and how this concern was addressed depends on the prespecified analysis plan. A multiplicity adjustment or hierarchy is not reported in the registry record, so the posted group estimates should not be treated as proof that all comparisons were confirmatory or independently tested.

How to understand missing observations

The primary outcome note states that one subject in the high-dose group had a missing Day 29 sample. The value could not be imputed according to the SAP rules, so that subject was excluded from this analysis. In general, excluding a participant with a missing outcome can affect an estimate if the reasons for missingness are related to the outcome or treatment. The record does not explain why the sample was missing or report sensitivity analyses for this exclusion. It also does not describe the full analysis population, beyond this specific exclusion note.

Sample-size illustrations on this page, if shown, are planning illustrations based on the observed effect and stated assumptions. They are not observed power and do not replace the trial’s own design rationale. The registry does not report a sample-size justification or the rationale for its planned enrollment. Likewise, no additional analysis plan, interim analysis procedure, or full set of contrast results is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome note identifies one missing Day 29 sample in the high-dose group. Because the value could not be imputed according to the SAP rules, the participant was excluded from this analysis. The record does not state why the sample was missing, whether missingness was related to treatment or viral load, or whether a sensitivity analysis assessed the effect of excluding this participant. Those details are not reported in the registry record.

The primary outcome description specifies the model, censoring boundary, and below-detection imputation, but does not describe the complete analysis population or all analysis-set definitions. The registry record does not report whether participants were analyzed according to randomized assignment, how protocol deviations were handled, or what other missing-data procedures were used. The specific Day 29 exclusion should therefore not be generalized into assumptions about the handling of other missing observations.

The trial has several dose groups and many outcomes, and the results include groups in two cohorts. The registry record does not report a multiplicity adjustment, testing hierarchy, or designation of which comparisons were confirmatory. It also does not report interim analyses or stopping rules. These absences do not establish that such procedures were not used; they mean the registry record does not describe them.

The stated study hypothesis focuses on the highest dose versus placebo, while the posted endpoint values show group-level estimates for multiple regimens. A direct contrast for the hypothesis, with its uncertainty and inferential result, is not reported in the registry record. Without that information, the displayed estimates cannot establish how the prespecified comparison was tested or how uncertainty across multiple comparisons was handled.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: drug overdose (14.3%), creatinine kinase high (12.5%), ast increased (12.5%).

The registry’s safety results distinguish serious adverse events from other adverse events. In Cohort 1 placebo, 1 of 8 participants is listed as affected by a serious adverse event; the low-, medium-, and high-dose groups list 0 of 6, 0 of 6, and 0 of 11, respectively. In Cohort 2 placebo, daily-dose, and weekly low-dose groups, the record lists 0 of 6 affected in each group. The weekly-dose group identified as Cohort 2 Group 4 lists 1 of 7 affected. No deaths are listed in any of these groups.

The record also identifies Drug overdose, Creatinine Kinase High, and AST increased among the top serious adverse event terms, with percentages of 14.3%, 12.5%, and 12.5%, respectively. These percentages are presented as registry figures; the record excerpt does not provide enough detail to infer their precise denominators or whether terms overlap. The event-term percentages should not be read as percentages of all trial participants unless the registry specifies that denominator.

These small group counts describe events recorded in the listed groups. They do not establish that one group is safer than another, and a zero in a group does not demonstrate that an event cannot occur. The registry reports a range of additional safety assessments, including vital signs, ECGs, laboratory assessments, and dengue infection-associated adverse events. Further interpretation of event severity, timing, relatedness, and exposure is limited because those details are not reported in the registry record.

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

The posted primary outcome results describe model-based estimates of DENV-3 viral-load AUC over Day 1 to Day 29 for several placebo and JNJ-64281802 groups. The values give a summary of viral-load exposure in this healthy-adult human challenge study. They are accompanied by 90% confidence intervals, which show uncertainty around the group estimates. One high-dose participant with a missing Day 29 sample was excluded from the primary analysis because the value could not be imputed under the SAP rules.

The registry’s brief summary frames the main hypothesis as whether the highest dose is superior to placebo for antiviral activity. However, the listed primary outcome results provide group estimates, not the direct treatment-placebo contrast and its uncertainty. The registry record does not report a p-value for that stated comparison in the posted primary outcome results. The estimates therefore should not be treated as a complete inferential answer to the main hypothesis or as evidence that one dose is definitively superior to another.

The endpoint concerns viral RNA in an experimental challenge setting, not a clinical outcome such as symptom burden or complications. It does not establish effects in populations outside the healthy adults studied, or in settings other than the dengue challenge model. The results also do not establish prevention or treatment effectiveness in ordinary clinical use. The registry record does not report enough information to make those broader inferences.

The safety figures are counts of affected participants in the listed groups and recorded serious adverse event terms. They are descriptive, with relatively small group sizes, and do not establish comparative safety. The absence of reported deaths in these groups is a description of the posted record, not proof that risk is absent.

Overall, the record supports a careful description of group-level viral-load estimates and safety counts. A fuller assessment of the trial’s central comparison would require the direct contrast, its uncertainty, and further analysis details that are not reported in the registry record. The results should be read within those limits rather than as a broad conclusion about clinical outcomes.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it measures antiviral activity in a controlled human challenge model using viral-load data collected over a defined period. The primary endpoint summarizes viral RNA across time rather than relying on a single measurement. That can be useful when the scientific question concerns the overall course of viral load, while also making the analysis dependent on how observations below the assay limit are handled.

The registry explicitly describes left censoring at 2.70 log10 copies/ml/days1-29, an assumed limit of detection of 36 copies/ml, and imputation of values <LOD with 18 copies/ml. These details matter: observations below detection are not simply ordinary measured values. The choice of model and assumptions about censored observations influence how the group estimates are derived and how they should be interpreted.

The trial also includes several dose groups and results from two cohorts, while its brief summary highlights a highest-dose-versus-placebo hypothesis. This makes it important to distinguish descriptive arm estimates from a formal contrast designed to test that hypothesis. The posted endpoint results provide group estimates and 90% confidence intervals, but not the direct contrast or its inferential result. The multiplicity approach and any interim procedures are also not reported in the registry record.

Finally, the registry identifies a specific missing Day 29 sample that led to exclusion from the primary analysis. Transparent reporting of such exclusions helps readers understand which observations contribute to the estimate. Taken together, these features make the record a useful example of why endpoint definition, censoring, missing-data handling, and contrast reporting all matter in interpreting a small, multi-group clinical trial.

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 primary analysis groups are small, and the posted results cover several dose groups across two cohorts. Estimates from small groups can be imprecise, as reflected in their confidence intervals. The registry record does not report a direct treatment-placebo contrast or its p-value alongside the group estimates, limiting interpretation of the study’s stated highest-dose hypothesis.

The primary outcome description reports a Tobit analysis, a censoring boundary, and an imputation value for results below the limit of detection. Further details about model diagnostics, sensitivity analyses, and the handling of other missing or censored data are not reported in the registry record. One high-dose participant with a missing Day 29 sample was excluded because imputation was not permitted under the SAP rules; the reason for the missing sample and the effect of this exclusion are not described.

The record lists a sequential model and describes sentinel enrollment in Cohort 1, but does not report the rules governing progression through groups, interim analyses, or stopping decisions. It also does not report a multiplicity strategy despite multiple dose groups and outcomes. Thus, it is not possible to determine from this record how the confirmatory status of comparisons or the overall false-positive risk was managed.

The posted outcome results include Cohort 2 groups, but detailed cohort-design information is not reported in the registry record. Dose amounts and schedules for the Cohort 1 groups are also not given in the record excerpt. The endpoint is viral-load AUC in healthy adults in a challenge model, so the record does not establish effects on clinical outcomes or in other populations. These are limits on interpretation, not evidence that additional information does not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Evaluation of Repeated Oral Doses of JNJ-64281802 Against DENV-3 Challenge — NCT05048875.
• Registry record last updated 2026-11-04; status last verified 2026-10.
• Results first posted 2025-04-24.
• 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

NCT05048875 is a completed Phase 2 randomized, placebo-controlled study of repeated oral JNJ-64281802 in healthy adults inoculated with Dengue Serotype 3. The registry lists a sequential model, triple masking, enrollment of 56, a start date of 2022-02-03, and primary completion on 2023-05-16. The official title describes the trial as doubleblind.

The primary outcome is log10 AUC DENV-3 RNA viral load from Day 1 through Day 29, analyzed using a Tobit analysis of variance model. The posted group results include placebo and treatment estimates for Cohort 1 and Cohort 2, with 90% confidence intervals. One high-dose participant with a missing Day 29 sample was excluded from the primary analysis.

The registry lists 32 outcome measures and 31 posted secondary outcomes. It reports group-level viral-load estimates and safety summaries, but a direct contrast for the stated highest-dose-versus-placebo hypothesis, multiplicity procedures, interim analyses, and fuller missing-data details are not reported in the registry record.