Study to Assess Safety and Activity of Combination Therapy of VRC07-523LS and Vorinostat on HIV-infected Persons: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess Safety and Activity of Combination Therapy of VRC07-523LS and Vorinostat on HIV-infected Persons (NCT03803605), a na phase 1 study. The primary outcome is Percent of Participants With a Grade 3 or Higher Treatment-Related Adverse Event (AE).

2. Clinical Question

The study also aimed to assess whether combining VRC07-523LS and vorinostat could affect non-active HIV virus. That aim is distinct from the registered primary endpoint, which concerns treatment-related adverse events. The registry record does not report a result for the primary endpoint or an analysis of the effect on non-active HIV virus.

The population and treatment schedule describe a small, early-phase investigation rather than a comparison of treatment strategies. With no control group, observations during the study cannot by themselves distinguish treatment effects from other explanations, such as changes over time or effects associated with continued ART. The record describes treatment exposure and some adverse-event counts, but does not establish a comparative estimate of safety or antiviral activity.

3. Trial Design

This was a Phase 1, completed, single-group study sponsored by the University of North Carolina, Chapel Hill. The registry lists enrollment of 15 participants, no masking, and allocation as NA. There was no randomized comparison group. The study began on 2019-02-12, and primary completion was recorded as 2021-01-28.

Participants were adults with HIV-1 infection who were receiving ART and met the stated CD4 T cell count and viral suppression criteria. The planned regimen comprised two series of combination therapy. Each series included one intravenous dose of VRC07-523LS followed by 10 oral doses of vorinostat, taken every 72 hours. The two series were separated by at least one month, and ART continued throughout the study. The brief summary describes participation as approximately 28 weeks, or about 7 months.

The primary endpoint’s stated observation period runs from the first day of study treatment through the end of study, described as approximately 36 weeks. The record therefore gives different approximate durations for participation and the primary endpoint timeframe; it does not explain that difference. These descriptions should not be treated as evidence of a specific participant’s actual follow-up duration.

The adverse-event listing includes 15 participants completing Step 1 and 8 receiving the combination therapy during Step 2. The registry does not explain why the Step 2 group is smaller, so the difference should not be attributed to withdrawals, eligibility decisions, or any other cause. Because the study has no concurrent control, its design can describe events observed during exposure but cannot provide a like-for-like treatment comparison.

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: Participants meeting the following advancement criteria in Step 1: a frequency of resting CD4+ T cell infection (RCI) \>0.30 per million cells proceeded to Step 2 and received the study intervention.

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.

6. Primary Endpoint

The registry lists the primary outcome as Percent of Participants With a Grade 3 or Higher Treatment-Related Adverse Event (AE), measured over First day of study treatment through end of study, a total of approximately 36 weeks.

The primary endpoint is the percentage of participants with a Grade 3 or higher treatment-related adverse event. The registry says safety was assessed using the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, corrected Version 2.1, July 2017. It defines Grade 3 as severe and Grade 4 as potentially life-threatening. An event counted as treatment-related if it was assessed as possible, probable, or definite in relation to study product, as defined in the protocol.

A severity threshold focuses attention on events judged to be more serious than mild or moderate symptoms. The percentage format expresses how often at least one qualifying event occurred among the participants in the relevant analysis population. It is not the same as a count of all events: one participant could have more than one event, while the endpoint concerns the proportion of participants meeting the criterion.

The stated timeframe extends from the first day of study treatment through the end of study, approximately 36 weeks. The registry record gives the endpoint definition and timeframe but does not report the endpoint’s observed percentage, numerator, or analysis details. The listed serious and other adverse-event counts are not a substitute for this result: seriousness, severity grade, and treatment relationship are separate classifications.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary percentage endpoint: whether a participant had at least one treatment-related adverse event meeting the Grade 3-or-higher threshold during the stated period. A participant-level percentage differs from an event count. If an individual experiences several qualifying events, that does not necessarily change the participant-level classification beyond whether the criterion was met. Conversely, an event count alone cannot reveal how many distinct participants met the endpoint.

The grading and attribution criteria are important to interpretation. The record identifies the DAIDS grading table and describes Grade 3 as severe and Grade 4 as potentially life-threatening. It also says treatment relationship could be assessed as possible, probable, or definite according to the protocol. These are distinct dimensions: an event can have a severity grade and a separate judgment about its relationship to study product. The registry’s general adverse-event counts do not show the grade and attribution for each event, so they cannot be used to reconstruct the primary endpoint.

A percentage estimate would ordinarily be interpreted alongside its denominator and a measure of uncertainty. A confidence interval is a range intended to convey the statistical uncertainty around an estimate under the method used to construct it. With a small group, the observed proportion can be imprecise, and a result of zero observed events does not imply that the underlying event risk is zero. The registry record does not report a confidence interval or the primary endpoint estimate, so no such interval can be interpreted for this outcome.

General: a single-group study describes outcomes among people who received the study regimen. Without a concurrent comparator, it cannot separate the association with treatment from other influences on the observed outcomes. A comparison to an external rate would require a suitable external source and assumptions about comparability; no such comparison is reported in the registry record. The observed adverse-event counts should therefore be read descriptively, not as a causal contrast.

The registry lists 15 participants completing Step 1 and 8 participants receiving the combination in Step 2. Those denominators correspond to differently described groups and treatment stages. The record does not state whether the Step 2 group is a subset of the Step 1 group, why the group sizes differ, or how participants with incomplete follow-up were handled for the primary endpoint. It would be inappropriate to combine the counts or infer a reason for the difference without those details.

The record reports one outcome measure and zero analyses. That means no analysis results are posted in the registry record, but it does not establish whether analyses were planned or conducted outside the record. No statistical model, interval-estimation method, hypothesis test, or approach to incomplete endpoint data is reported. In the absence of these details and a posted endpoint result, there is no basis for evaluating the precision or statistical significance of the primary outcome.

General: over-dispersion matters when a statistical model assumes less variation than the data contain. If that occurs, standard errors can be too small and uncertainty can be understated. This trial’s registry record does not report an analysis model or a dispersion parameter, and its binary participant-level endpoint does not itself supply the information needed to assess over-dispersion. No claim about this issue can be made for the trial’s analysis.

The sample-size assumptions describe a planning illustration, not the study’s own design justification or observed power. The stated illustration uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. These are hypothetical planning assumptions, while the actual trial is single-group and has no randomized two-arm comparison. The registry record does not report the trial’s sample-size justification, and an illustration based on assumed effects should not be interpreted as evidence that the study had a particular probability of detecting an effect.

General: multiplicity arises when several hypotheses or outcomes are tested, because repeated testing can increase the chance of a false-positive finding if each test is interpreted in isolation. The record lists one outcome measure and no analyses, but does not describe a multiplicity strategy or the full analysis plan. It is not possible to determine from the registry whether any broader family of analyses was planned or how it would have been handled.

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("VRC07-523LS + Vorinostat (VOR)")
n      <- c(8)
events <- c(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  VRC07-523LS + Vorinostat (VOR)  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and zero analyses. It does not report a statistical analysis plan, a multiplicity adjustment, or how any set of multiple tests would have been handled. The stated study aims include safety and possible impact on non-active HIV virus, but the posted record does not provide analyses of those aims. The existence of multiple aims does not by itself show that multiple statistical tests were performed.

The record also does not report how missing or incomplete outcome information was handled. It does not state whether all participants contributed to the primary endpoint analysis, whether follow-up was complete, how incomplete observations were classified, or whether any imputation was used. The different denominators in the adverse-event listing—15 participants completing Step 1 and 8 receiving the Step 2 combination—do not explain participant flow or missingness.

Analysis populations are described only through the labels attached to those adverse-event groups. The record does not define an intention-to-treat, per-protocol, or other analysis population for the primary endpoint. Nor does it explain which participants were included in any endpoint calculation. Since the primary endpoint result and its analysis are not reported, missing-data handling and population selection cannot be evaluated from this record.

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

The registry lists 0 serious adverse events among 15 participants completing Step 1, and 0 among 8 participants receiving VRC07-523LS plus vorinostat during Step 2. It lists 0 deaths in each group. The Step 1 and Step 2 denominators describe different stages or group definitions; the record does not explain the relationship between them, so they should not be added together.

The listing also reports other adverse events in 14 of 15 Step 1 participants and 8 of 8 Step 2 participants. Those counts are not the primary endpoint result. A serious adverse event is not interchangeable with a Grade 3-or-higher event, and neither classification alone identifies whether the event was considered treatment-related. The registry record does not break down the other adverse events by grade or attribution in these counts.

Zero recorded serious events in these groups is a description of the posted observations, not a guarantee of no risk. The primary endpoint’s percentage of participants with a treatment-related Grade 3-or-higher event is not reported in the registry record.

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

The posted results describe a small Phase 1 study with no concurrent comparator. The adverse-event listing records no serious adverse events and no deaths in the two listed groups. It also records other adverse events among participants in both groups. These observations are useful as a record of what was counted in the study, but the registry does not provide the event-level detail needed to determine severity grades or treatment attribution for those other events.

The central safety outcome is the percentage of participants with a treatment-related Grade 3-or-higher adverse event. Although the registry gives its definition and observation period, it does not report the endpoint result. The listed serious-event counts cannot fill that gap. The record also does not post an analysis of the study’s other aim concerning non-active HIV virus.

Nothing in these data establishes a comparison with another treatment or with no study combination. Without a control group, differences in outcomes cannot be attributed to the regimen through a randomized contrast. The absence of a reported serious event in the listed groups is not equivalent to demonstrating that serious events are impossible or that a particular treatment strategy is safer than another.

The study describes a selected population of adults with HIV-1 infection who were on ART and met the stated immune and viral suppression criteria. Its findings, even if additional outcome details were available, would be most directly relevant to people resembling that study population and regimen context. The registry record does not support broader claims about other populations, treatment schedules, or clinical outcomes.

Accordingly, the record permits a limited descriptive reading of enrollment, treatment design, and listed adverse-event counts. It does not permit a quantitative interpretation of the primary safety endpoint, an estimate of comparative effect, or a conclusion about antiviral activity.

14. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in early-phase research: the goal may include characterizing safety and exploring biological activity, while the posted registry information may contain only partial outcome detail. A clearly defined primary safety endpoint is useful because it specifies the event threshold, attribution criteria, and observation period. Those definitions make clear what a complete result would need to summarize.

The distinction among event counts, serious adverse events, severity grades, and treatment relationship is especially important. They answer different questions. A count of participants with any listed adverse event does not reveal how many met a particular severity threshold, and a serious-event count does not establish the number considered treatment-related. Reading these categories as interchangeable can misstate what the record shows.

The design also matters. With one group and no masking, the study can describe events occurring during the regimen, but it cannot estimate a treatment contrast against a concurrent control. This is not a defect in the reporting of a randomized comparison; there was no such comparison in the design. It does mean that statistical interpretation should remain descriptive and should not imply causal or comparative conclusions.

Finally, a stated objective is not itself a result. The registry describes an interest in whether the combination might affect non-active HIV virus, but does not report an analysis answering that question. Separating study rationale, endpoint definitions, observed counts, and analyzed outcomes helps readers recognize which conclusions are supported by the record and which remain unresolved.

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 registry record does not report the primary endpoint estimate, its numerator, an uncertainty interval, or a statistical test. Consequently, the main registered safety outcome cannot be interpreted quantitatively from the posted information. The serious and other adverse-event counts do not provide the severity and treatment-attribution detail required to reconstruct it.

The study is single-group, with no randomized comparator and no masking. The observed counts therefore do not provide a controlled estimate of the safety or activity of the combination. The record does not report an analysis of non-active HIV virus, despite listing that as a study purpose.

The adverse-event listing uses different group descriptions and denominators: 15 participants completing Step 1 and 8 receiving combination therapy during Step 2. Reasons for the different group sizes and details of participant flow are not reported in the registry record. The record also does not describe the analysis population or how incomplete outcome data were handled.

There is a difference between the approximate 28-week study duration described in the brief summary and the approximately 36-week timeframe stated for the primary endpoint. The registry record does not explain the difference. The listed results do not establish each participant’s follow-up duration.

The enrollment of 15 and the early-phase design limit how much can be inferred from the observed counts. The registry record does not report a sample-size justification, statistical analysis plan, or details of any interim analyses. These absences prevent assessment of the intended precision, planned handling of uncertainty, and completeness of the posted analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Assess Safety and Activity of Combination Therapy of VRC07-523LS and Vorinostat on HIV-infected Persons — NCT03803605.
• Registry record last updated 2021-12-02; status last verified 2021-07.
• Results first posted 2021-12-02.
• 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

NCT03803605 is a completed Phase 1, single-group study sponsored by the University of North Carolina, Chapel Hill. It enrolled 15 adults with HIV-1 infection and evaluated two series of VRC07-523LS followed by oral vorinostat, with ART maintained throughout the study. The study began on 2019-02-12, with primary completion recorded as 2021-01-28.

The primary outcome concerns the percentage of participants with a treatment-related Grade 3-or-higher adverse event. The registry record defines the outcome but does not report its result or an analysis. The adverse-event listing reports no serious adverse events and no deaths in the listed Step 1 and Step 2 groups, alongside other adverse events in both groups. These counts do not establish the primary endpoint result or an effect on non-active HIV virus.