Evaluating the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered in Multiple Doses and Routes to Healthy, HIV-uninfected Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered in Multiple Doses and Routes to Healthy, HIV-uninfected Adults (NCT03387150), a randomized phase 1 study. The primary outcome is Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness.

2. Clinical Question

The trial’s stated purpose was to evaluate safety, tolerability, and serum concentrations of VRC07-523LS given in multiple doses and routes to healthy, HIV-uninfected adults. The primary endpoint is specifically about local reactogenicity signs and symptoms—pain and/or tenderness—not serum concentration or an HIV-related clinical outcome. The registry record also lists antidrug antibodies and neutralizing antibody responses among secondary outcomes.

The available registry entries identify the groups and the endpoint definition, but do not report the number of participants with pain or tenderness in each group. They also do not report a statistical comparison for that primary endpoint. As a result, the registry record does not allow the primary question to be answered from the posted results. The trial description supports understanding what was intended to be measured, but not a conclusion about the frequency or comparative pattern of those symptoms.

3. Trial Design

The registry record identifies NCT03387150 as a randomized, parallel-group Phase 1 trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). It reports an enrollment of 124 and a completed status. The start date is 2018-02-28, and the primary completion date is 2020-12-07. The official title describes the trial as multicenter and partially blinded, while the registry’s masking field is listed as none. These entries therefore do not give a consistent description of masking.

Six groups received VRC07-523LS. Three intravenous groups were assigned doses of 2.5 mg/kg, 5 mg/kg, or 20 mg/kg. Two subcutaneous groups received 2.5 mg/kg or 5 mg/kg, and one intramuscular group received 2.5 mg/kg. A seventh group received placebo by intramuscular injection. The arm descriptions specify administrations at Weeks 0, 16, 32, 48, and 64. The record gives the placebo dose as 2.5 mg/kg.

Randomized allocation describes how participants were assigned, but the registry record does not report the allocation ratio or the method used to generate the random sequence. It also does not describe whether any masking applied to particular participants, investigators, or assessments. Those details should not be inferred from the title or from the masking field alone.

The trial’s primary outcome concerns participants reporting local pain and/or tenderness, using the maximum grade observed during the assessment window after each administration. The record lists secondary outcomes concerning antidrug antibodies and neutralizing antibody responses. Although it describes the planned outcome domains and dose routes, it does not report the primary endpoint’s group-level results or an analysis comparing groups.

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 7 groups are shown.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

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

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness, measured over Measured through 3 days after each vaccine dose at Weeks 0, 16, 32, 48, 64.

The primary endpoint is the number of participants reporting local pain and/or tenderness. The registry describes the measure as a count of participants and says that symptoms are graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. For each symptom, the maximum grade observed over the assessment period is presented.

The assessment period is through 3 days after each study-product dose at Weeks 0, 16, 32, 48, and 64. This definition focuses on local symptoms occurring soon after administration and captures the most severe recorded grade for each participant’s symptom over the stated window. Counts of participants can be useful for describing how many people experienced a specified event, while the grading system adds information about recorded severity.

The registry record does not provide the numbers of participants reporting pain or tenderness, the grade-specific results, or group-level comparisons. It also does not specify in the endpoint description how missing symptom assessments were handled. Therefore, the endpoint’s definition is available, but its observed results and their precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the design as randomized and parallel-group. In a randomized trial, assignment is intended to reduce systematic differences between groups at the point of assignment. A parallel-group design means participants are assigned to a group and followed within that group rather than switching between the listed study products. These general design features do not by themselves establish how allocation was performed, whether groups remained comparable during follow-up, or what statistical model was used. Those methods are not reported in the registry record.

What does the endpoint count?

The primary outcome is a participant count for local pain and/or tenderness. A binary event outcome generally records whether each participant did or did not meet a defined event criterion. Here, the registry’s endpoint title identifies symptoms, while its description says severity is graded and the maximum grade observed for each symptom is presented. The posted record does not include the corresponding counts by grade or group. Because the endpoint is observed after repeated scheduled administrations, a complete analysis would need to make clear how participant-level records across those assessment periods were summarized. That analysis approach is not reported in the registry record.

What would a confidence interval convey?

In general, a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while neither width nor position establishes clinical importance on its own. No confidence intervals for the primary endpoint are reported in the registry record. No primary-endpoint estimates are reported either, so precision cannot be assessed from this record.

What can be inferred from counts?

Counts are direct descriptions of how many participants were recorded with an event, but their interpretation depends on the number assessed and the event definition. The adverse-event summary supplies counts at risk and counts affected for serious and other events. Those figures can be read as group-level descriptions, but they do not provide an adjusted or unadjusted comparison estimate, uncertainty interval, or hypothesis test. The record does not report whether the safety summaries were analyzed using a formal statistical model.

What do the analysis fields establish?

The registry record lists 12 outcome measures and zero analyses. This indicates that outcome measures are listed without analyses in the posted record; it does not establish what analyses may have been conducted outside the record. The primary outcome is flagged as involving several categories or time points and not being reduced to one comparison. Consequently, a single recalculated comparison is not available from the posted summary statistics. No sponsor analysis for the primary endpoint is included, and no recalculated estimate should be substituted for one.

How should the planning illustration be understood?

The registry record includes general assumptions for a planning illustration based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. Such calculations, when reported, are planning illustrations; they are not observed power and do not describe the trial’s original sample-size justification. No numerical planning estimates are reported in the registry record. The trial’s sample-size justification, assumptions used at design, and any interim analyses are not reported in the registry record.

Why does the dose and route structure matter?

The trial includes several dose and administration-route groups, as well as an intramuscular placebo group. A statistical comparison across this structure would need to identify which groups were compared and how multiple comparisons were handled. The registry record does not report a statistical analysis plan or specify a primary contrast among these groups. It would therefore be inappropriate to assume that all active groups were compared with placebo, that dose-response was tested, or that a particular route comparison was prespecified.

General statistical interpretation also depends on the handling of missing observations, analysis populations, and multiplicity. Because these details are not reported, the posted record does not support claims about adjusted estimates, robustness to missing data, or control of false-positive findings across multiple outcomes or comparisons.

10. Multiplicity, Missing Data and Analysis Populations

The trial has several active dose-and-route groups, a placebo group, a primary endpoint assessed after repeated administrations, and secondary outcomes. When multiple outcomes, groups, or time points are considered, multiplicity is a general statistical concern: examining many comparisons can increase the chance of at least one apparently notable result by chance. Whether and how that concern was addressed depends on the prespecified analysis plan. The statistical plan and any multiplicity procedure are not reported in the registry record.

The record says the primary outcome has several categories or time points and is not reduced to one comparison. It lists 12 outcome measures and zero analyses. The registry record does not identify a primary contrast among the groups or report a hierarchy for testing outcomes. It also does not report interim analyses. No assumptions about those procedures can be made from the listed design alone.

Missing-data handling is not reported in the registry record. In general, missing observations can affect an estimate if participants with unobserved outcomes differ from those with observed outcomes. The record does not state how many participants had missing primary endpoint assessments, how missing assessments were handled, or whether any sensitivity analyses were conducted.

The analysis populations are also not reported in the registry record. The enrollment figure does not establish which participants were included in each outcome analysis, nor does it establish whether the analyses followed randomized assignment or another population definition. The posted adverse-event counts include group-specific numbers at risk, but they do not explain the analysis population rules or missingness for the primary endpoint. These omissions limit assessment of the reliability and scope of any comparative interpretation.

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: any event in soc (5.3%), staphylococcal infection (5.3%), calculus urinary (5.3%), pyrexia (4.8%).

The adverse-event summary distinguishes serious events from other events and gives, for each group, the number at risk and the number affected. Serious-event counts are 1 of 19, 1 of 19, 0 of 21, 1 of 21, 0 of 20, 0 of 21, and 0 of 3 across Groups 1 through 7, respectively. The record lists 0 deaths for every group. These counts describe what is posted for the groups; they are not estimates of comparative risk and are not accompanied by confidence intervals or statistical tests.

The registry also lists “Any Event in SOC” and “Staphylococcal infection” at 5.3%, “Calculus urinary” at 5.3%, and “Pyrexia” at 4.8% among the top serious-event terms. The record does not provide further detail about the denominator or how the terms relate to individual participants, so the percentages should be read as registry-reported summaries rather than as group-specific estimates.

Seriousness does not establish that an event was caused by study product. The registry record does not state in this summary whether the listed events were considered related to treatment. Likewise, a zero in a group is a description of the observed registry count, not evidence that an event could not occur. The small placebo-group count warrants particular care in interpreting that group’s descriptive summary.

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

The registry record establishes that this was a randomized Phase 1 study of VRC07-523LS across multiple doses and routes in healthy, HIV-uninfected adults, with an intramuscular placebo group. It defines local pain and/or tenderness as the primary endpoint and describes how severity was to be graded and over what post-administration period symptoms were assessed. It also posts group-level counts for serious and other adverse events and reports no deaths in the listed groups.

Those details do not show whether the primary endpoint was more or less frequent in any group. The number of participants reporting pain or tenderness, the severity-grade results, and statistical comparisons are not reported in the registry record. The adverse-event counts are descriptive and do not establish a causal relationship with study product or a statistical difference between groups. No serum concentration results are included in the registry entries, despite serum concentrations being part of the stated study purpose.

The trial’s Phase 1 designation and focus on safety, tolerability, and serum concentrations describe its study context, not a conclusion about clinical benefit. The record does not report findings that would establish effectiveness against HIV infection, and the posted outcomes should not be interpreted as evidence of prevention or treatment efficacy. Its secondary outcome descriptions identify antidrug antibodies and neutralizing antibody responses as topics of assessment, but their results are not reported in the registry record.

In general, an estimate is more informative when accompanied by a measure of precision and a clear account of the analysis population. Those elements are unavailable for the primary endpoint in this record. The appropriate reading is therefore limited: the study design and outcome definitions are documented, and some safety summaries are posted, but the available registry information does not support a conclusion about the primary endpoint’s frequency, comparative pattern, or precision.

13. Why This Trial Matters Statistically

This trial is statistically notable for the structure of its intervention groups: several doses are administered by different routes, alongside an intramuscular placebo group. That design can support questions about safety and serum concentrations across regimens, but interpretation depends on clearly defined comparisons and adequate reporting of group-level outcomes. The registry record describes the groups but does not identify a statistical contrast or provide primary endpoint analyses.

The primary outcome also involves symptoms assessed after repeated scheduled administrations and uses a maximum severity grade over each stated assessment period. Such an outcome definition makes the participant-level summary and the handling of repeated observations important to interpretation. The registry record provides the endpoint definition, but not the results or the analysis method used to summarize observations across assessments.

The posted adverse-event information illustrates why counts should be read alongside their denominators and with attention to group size. The placebo group has 3 participants at risk in the serious-event summary, while the active groups have larger listed denominators. Descriptive counts from groups of different sizes are not, by themselves, a fair basis for comparing event frequency or uncertainty. The record provides no formal comparative safety analysis.

Finally, the record distinguishes the existence of outcome measures from the reporting of analyses: it lists 12 outcome measures and zero analyses. That gap matters because the trial’s dose-and-route structure and multiple outcome domains raise questions about comparison selection, multiplicity, and analysis populations. Since those methods and primary results are not reported, readers can identify the intended questions but cannot reconstruct the statistical evidence needed to answer them.

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 central limitation is that the primary endpoint’s results are not reported in the registry record. The record defines local pain and/or tenderness, its grading approach, and the assessment window, but does not provide participant counts by group, grade-specific findings, or a comparative estimate. The absence of those results prevents assessment of the primary endpoint’s observed frequency and precision.

The registry reports no analyses, and its primary-outcome note indicates that several categories or time points were not reduced to one comparison. The statistical analysis plan, allocation ratio, random-sequence method, analysis populations, handling of missing observations, and multiplicity procedures are not reported in the registry record. Interim analyses and the original sample-size justification are also not reported in the registry record.

The record’s description of masking is inconsistent: the official title calls the trial partially blinded, whereas the masking field says none. The available information does not explain this discrepancy or specify who, if anyone, was masked. The group-level safety summaries are descriptive and do not state whether events were judged related to study product. The serious-event percentages are listed without accompanying group-specific context in the summary, limiting interpretation of their denominators and overlap.

Although the study purpose includes serum concentrations, no serum concentration results are included in the registry entries available for this analysis. The secondary outcomes are named, but results for antidrug antibodies and neutralizing antibody responses are not reported in the registry record. These limitations mean that the posted details primarily support a description of study design, endpoint definitions, and selected safety counts—not a complete evaluation of trial outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluating the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered in Multiple Doses and Routes to Healthy, HIV-uninfected Adults — NCT03387150.
• Registry record last updated 2023-04-05; status last verified 2023-04.
• Results first posted 2022-03-21.
• 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

NCT03387150 is a completed randomized, parallel-group Phase 1 trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The registry reports enrollment of 124 healthy, HIV-uninfected adults and describes six VRC07-523LS groups using intravenous, subcutaneous, or intramuscular administration, plus an intramuscular placebo group. The listed dosing schedule is at Weeks 0, 16, 32, 48, and 64.

The primary endpoint is the number of participants reporting local pain and/or tenderness, graded using the stated adverse-event grading system. Primary endpoint results and statistical analyses are not reported in the registry record. The safety summary lists serious and other event counts by group and reports no deaths. The record also lists secondary outcomes for antidrug antibodies and neutralizing antibody responses, but their results are not reported in the registry record.