A Study to Assess Safety and Immunogenicity of Conserved Mosaic HIV-1 Vaccines: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess Safety and Immunogenicity of Conserved Mosaic HIV-1 Vaccines (NCT04586673), a non-randomized phase 1 study. The primary outcome is Assessement of Safety.

2. Clinical Question

3. Trial Design

This was a Phase I dose-escalation, open-label, non-randomized trial of candidate conserved mosaic HIV-1 vaccines. Its official title describes sequential administration of ChAdOx1- and MVA-vectored vaccines to healthy HIV-1 negative adult volunteers in Oxford, UK. The registry records the trial as completed, with enrollment of 13. The recorded start date is 2021-07-03 and the primary completion date is 2022-08-03.

The brief summary describes 3 volunteers receiving a low dose of ChAdOx1.tHIVconsv1. A further 10 volunteers received a higher dose of ChAdOx1.tHIVconsv1, followed by a vaccination each of MVA.tHIVconsv3 and MVA.tHIVconsv4 4 weeks later. The arm descriptions specify the vaccine quantities: 5 x 10^9 vp for low-dose ChAdOx1.tHIVconsv1; 5 x 10^10 vp for higher-dose ChAdOx1.tHIVconsv1; 1 x 10^8 pfu for MVA.tHIVconsv3; and 0.9 x 10^8 pfu for MVA.tHIVconsv4.

The primary outcome was safety, expressed as a count of participants with vaccine-related serious adverse events during the 140 days after enrollment. A secondary outcome concerned assessment of immunogenicity after sequential administration of the vaccines. The registry lists 4 outcome measures but does not report immunogenicity findings in this record. It lists no statistical analyses. Details of dose-escalation decision rules, the statistical analysis plan, and any interim review are not reported in the registry record.

Because allocation was non-randomized and the groups received different regimens, the group counts are descriptive rather than a controlled comparison. Open-label status means masking was not used. The registry does not describe a parallel placebo or untreated group. These design features matter when interpreting both the adverse-event counts and any attempt to separate the effects of individual vaccine components.

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

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: HIV-1/2-negative low risk males and females,18-65 years of age

6. Primary Endpoint

The registry lists the primary outcome as Assessement of Safety, measured over 140 days.

The primary endpoint is the count of participants with vaccine-related serious adverse events collected up to day 140 after enrollment. It is a binary participant-level outcome: each participant either has at least one qualifying event in the defined period or does not. The registry identifies the unit as participants and describes the outcome as the proportion of volunteers with vaccine-related serious adverse events.

Serious adverse events are used in clinical research to capture important safety events, rather than every symptom or event that may occur during observation. Their use as an endpoint can help organize safety monitoring around events classified as serious. The registry record does not provide the criteria used to classify seriousness, the process for judging vaccine relatedness, or the event-level descriptions. Those details are not reported in the registry record.

The reported timeframe is 140 days after enrollment. This defines the observation window relevant to the endpoint; it does not establish what happened outside that window. The posted count is zero participants with vaccine-related serious adverse events in the low-dose group and zero in the higher-dose group. These counts are descriptive observations in the enrolled groups. They do not by themselves establish the probability of an event in a broader population or demonstrate that a vaccine is safe.

The study also aimed to assess immunogenicity, but the immune response results are not reported in the registry record. The primary safety endpoint should therefore be kept distinct from the stated secondary immune-response objective: the recorded safety counts cannot answer the immunogenicity question.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a count of participants with an event, with the endpoint described as the proportion of volunteers with vaccine-related serious adverse events. For this kind of binary outcome, the event status is recorded at the participant level: a participant either meets the outcome definition during the observation window or does not. The posted summaries give the number at risk and the number affected for each group. These counts are directly interpretable as descriptions of the enrolled groups, but a count alone does not quantify uncertainty about what might occur in a wider population.

What does a confidence interval add?

In general, a confidence interval expresses statistical uncertainty around an estimate. It gives a range of values compatible with the observed data under the assumptions of the method used. It is not a guarantee that the true value lies in the interval, and it does not account automatically for design limitations such as non-random allocation or incomplete outcome measurement. The registry record does not report confidence intervals for the primary safety outcome, so the precision of an interval estimate cannot be described from this record.

When no events are observed, the observed event count is still informative, but it should not be interpreted as proof that the underlying event probability is zero. With limited observations, rare outcomes may not occur in the observed group even if they can occur. This is a general feature of event-count data, not evidence that an unrecorded event happened in this study. The registry reports zero participants with vaccine-related serious adverse events in both groups; it does not report an inferential analysis of these counts.

Why does the design affect interpretation?

Random allocation is used in general to make assigned groups comparable in expectation, helping support causal comparisons. This trial was non-randomized, and the registry explicitly notes that the arms are not a like-for-like control comparison. The regimens also differ: one group received low-dose ChAdOx1.tHIVconsv1, while the other received higher-dose ChAdOx1.tHIVconsv1 followed by MVA.tHIVconsv3 and MVA.tHIVconsv4. The group contrast therefore combines differences in ChAdOx1 dose and the presence of the MVA vaccinations. It cannot isolate the contribution of a single component.

Open-label means masking was not used. In general, lack of masking can affect how events are noticed, reported, assessed, or attributed, depending on the outcome and procedures. The registry does not describe the event collection and adjudication procedures in enough detail to assess those possibilities for this trial. It also does not report a randomized comparator that could provide a direct estimate of background event experience under a different intervention.

What do the planning assumptions mean?

The registry’s sample-size assumptions describe planning illustrations based on an observed effect, not the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the stated convention is a total number of events using the Schoenfeld method; other outcomes use participants per arm. Such illustrations are hypothetical planning calculations. They are not observed power, do not show that the trial was designed with those assumptions, and do not establish that an effect was detected.

For a binary outcome, general sample-size planning depends on the event rates assumed, the effect considered meaningful, the chosen significance level, the desired power, and the allocation scheme. Those assumptions affect the required number of participants. The registry does not report a trial-specific sample-size justification or a statistical plan for the primary endpoint. No sample-size value or power conclusion should be inferred from the posted event counts alone.

How should event categories be handled?

The primary endpoint concerns vaccine-related serious adverse events, while the adverse-event summary also contains an “other” category. In general, categories should be interpreted according to their prespecified definitions, collection procedures, and rules for attribution. The record does not report the detailed definitions or the event-level data needed to examine overlaps, timing, or classification. Accordingly, the summary counts can be repeated as recorded, but they cannot support a more detailed account of event type or severity.

The registry lists no statistical analyses. It does not report a model, hypothesis test, adjusted estimate, confidence interval, or analysis population for the primary safety endpoint. No adjusted or causal result should be inferred. The posted counts are best understood as descriptive registry results for the recorded groups and observation window.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("ChAdOx1.tHIVconsv1 Low Dose", "ChADOx1.tHIVconsv1 Higher Dose")
n      <- c(3, 10)
events <- c(0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  ChAdOx1.tHIVconsv1 Low Dose  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  ChADOx1.tHIVconsv1 Higher Dose  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures and identifies safety as the primary outcome, with immunogenicity as a secondary objective. When a study examines multiple outcomes, time points, or comparisons, general statistical practice considers whether multiple testing could increase the chance of a misleading positive finding. A prespecified hierarchy or multiplicity adjustment can address that issue, but neither a multiplicity plan nor a statistical analysis plan is reported in the registry record. The record also lists no statistical analyses. Therefore, no adjustment strategy or interpretation of multiple hypothesis tests can be assessed.

The registry states that the primary safety outcome was collected up to day 140 after enrollment. It does not describe how missing safety observations were handled, whether all enrolled participants contributed to the endpoint summary, or how incomplete follow-up would affect the analysis. Missing-data methods and the analysis population are not reported in the registry record. The adverse-event summary does give the number at risk in each group, but that information alone does not establish the completeness of follow-up or the handling of missing information.

The record does not state whether participants were analyzed according to enrollment, vaccine received, or another population definition. It also does not report rules for excluding observations or handling protocol deviations. These omissions limit assessment of how the posted counts were derived and whether all eligible observations were included. Immune-response results and their analysis populations are not reported in the registry record either.

12. 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

For vaccine-related serious adverse events through day 140 after enrollment, the registry records 0 affected participants among 3 at risk in the low-dose group and 0 affected among 10 at risk in the higher-dose group. These are participant counts within the registry’s stated endpoint and follow-up window. They are not a guarantee that such events cannot occur, and they do not establish a zero underlying risk.

The adverse-event summary separately lists 3 of 3 participants in the low-dose group and 10 of 10 in the higher-dose group under other adverse events. The registry does not provide descriptions for the terms in this category in the record. The “other” counts should not be read as counts of serious events, nor do they identify specific symptoms, causes, or severity levels. No deaths are recorded in either group.

In general, safety counts are most useful when read with event definitions, ascertainment procedures, follow-up completeness, and uncertainty estimates. The registry does not report those details or confidence intervals for these outcomes. The small enrolled groups and the non-randomized, different-regimen design also limit comparisons. The figures describe the posted observations; they do not establish comparative safety or rule out uncommon events.

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

The registry records that no participants in either group had a vaccine-related serious adverse event during the stated 140-day period. This is a description of the primary safety outcome among the participants included in the record. It is not a claim that serious adverse events are impossible, nor does it show that the underlying event probability is zero. The record does not report confidence intervals that would convey statistical uncertainty around the observed counts.

The design places important limits on interpretation. This was a non-randomized, open-label study without a described separate control intervention. The two groups also received different regimens: the higher-dose group received MVA.tHIVconsv3 and MVA.tHIVconsv4 after higher-dose ChAdOx1.tHIVconsv1, unlike the low-dose group. Consequently, the counts do not provide a clean comparison of vaccine dose, individual components, or the sequential regimen against a control.

The trial’s stated aims included assessment of immune responses, but immunogenicity results are not reported in the registry record. The safety counts cannot answer whether immune responses were generated or characterize their magnitude or duration. Likewise, zero recorded vaccine-related serious adverse events within the stated period does not establish what might occur beyond that period or in populations not represented by the enrolled volunteers.

The registry also reports other adverse-event counts and no deaths, but it does not give event-level descriptions or detailed classification procedures. The “other” category should therefore be understood only as the registry’s recorded category, not as a specific clinical outcome. Overall, the results are a limited descriptive account of observed safety events in this trial, not a definitive estimate of risk or evidence of comparative effects.

14. Why This Trial Matters Statistically

This trial illustrates how early-phase safety results need to be read in relation to the design that produced them. The primary outcome is expressed as participants with vaccine-related serious adverse events, and the registry reports zero in each group during the stated follow-up window. The statistic is straightforward to describe, but its interpretation depends on the number observed, the outcome definition, follow-up, and the design of the comparison.

The non-randomized, sequential structure is especially important. The groups did not receive interchangeable regimens: the higher-dose group also received two MVA vaccines. That means the group labels do not isolate a single treatment difference. Even when the recorded serious-event counts are the same, the data do not demonstrate that the regimens are equivalent or that one component has a particular safety effect.

The example also distinguishes absence of observed events from evidence of absence. In general, a zero count in a limited study can coexist with uncertainty about uncommon events. Confidence intervals, transparent follow-up information, and clearly stated analysis methods help readers understand that uncertainty. The registry record does not report these statistical details for the primary endpoint.

Finally, the record separates the stated safety objective from the immunogenicity objective. Safety counts cannot substitute for immune-response results, and those results are not reported in the registry record. Statistically, the trial matters as a reminder that endpoint-specific evidence, design limitations, and reporting completeness all shape what can be concluded from clinical trial data.

15. 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 enrollment was 13, and the safety summary divides participants between the low-dose and higher-dose regimens. This limits how much the observed counts can establish about uncommon events. The registry does not report confidence intervals or another uncertainty measure for the primary endpoint, so the precision of the observed event counts is not quantified in the record.

Allocation was non-randomized, masking was absent, and the arms were not like-for-like controls. The regimens differed in both the ChAdOx1.tHIVconsv1 dose and whether MVA.tHIVconsv3 and MVA.tHIVconsv4 were given. Consequently, group comparisons cannot isolate a dose effect or identify the effect of an individual vaccine component. There is no separate control intervention described in the registry record.

The primary safety outcome was collected up to day 140 after enrollment. The record does not report event-level descriptions, detailed definitions for seriousness or vaccine relatedness, ascertainment procedures, or completeness of follow-up. It also does not report how missing observations were handled, which participants were included in each analysis population, or a statistical analysis plan. These gaps restrict evaluation of how the endpoint was classified and analyzed.

Although immunogenicity was a stated objective, immune-response results are not reported in the registry record. The record lists 4 outcome measures but no statistical analyses. It therefore does not permit assessment of multiplicity procedures, adjusted comparisons, or the analysis of secondary outcomes. These limitations concern what can be interpreted from the registry record and do not establish that unreported procedures or analyses were absent from the conduct of the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Assess Safety and Immunogenicity of Conserved Mosaic HIV-1 Vaccines — NCT04586673.
• Registry record last updated 2025-04-29; status last verified 2023-08.
• Results first posted 2024-09-03.
• 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.

19. Record Summary

NCT04586673 is a completed Phase I, non-randomized, open-label study of candidate ChAdOx1- and MVA-vectored conserved mosaic HIV-1 vaccines in healthy HIV-1 negative adult volunteers. The registry records enrollment of 13, a start date of 2021-07-03, and a primary completion date of 2022-08-03.

The low-dose group received ChAdOx1.tHIVconsv1 at 5 x 10^9 vp. The higher-dose group received ChAdOx1.tHIVconsv1 at 5 x 10^10 vp, followed by MVA.tHIVconsv3 at 1 x 10^8 pfu and MVA.tHIVconsv4 at 0.9 x 10^8 pfu. The primary safety outcome was vaccine-related serious adverse events through day 140 after enrollment. The registry records 0 affected participants in each group and no deaths.

Immunogenicity was also a stated objective, but those results are not reported in the registry record. The record lists no statistical analyses, and details of missing-data handling, analysis populations, and a trial-specific statistical plan are not reported.