Evaluating the Safety, Pharmacokinetics, and Anti-Viral Activity of VRC01 and VRC01LS in the Serum and Mucosa of Healthy, HIV-Uninfected Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating the Safety, Pharmacokinetics, and Anti-Viral Activity of VRC01 and VRC01LS in the Serum and Mucosa of Healthy, HIV-Uninfected Adults (NCT02797171), a randomized phase 1 study. The primary outcome is Number of Participants Reporting Local Reactogenicity Signs and Symptoms.

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, unmasked, parallel-group study evaluating VRC01 and VRC01LS in healthy, HIV-uninfected adults. The registry lists an enrollment of 80 and the condition HIV Infections. The study status is Completed. Its listed start was 2017-03-01, and its primary completion was 2019-06-05. The sponsor was the National Institute of Allergy and Infectious Diseases (NIAID).

The intervention groups varied by antibody, dose, and administration schedule. Group 1 received VRC01 at 10 mg/kg at Months 0, 2, 4, and 6. Group 2 received VRC01 at 30 mg/kg at Months 0, 2, 4, and 6. Group 3 received VRC01LS at 30 mg/kg at Months 0, 3, and 6. Group 4 received VRC01 at 30 mg/kg at Month 0, while Group 5 received VRC01LS at 30 mg/kg at Month 0. Consequently, a contrast between groups could reflect differences in product, dose, schedule, or more than one of these features.

The registry identifies random allocation and a parallel model but does not report the allocation method, masking, or additional details about the randomization process beyond stating that masking was none. It does not report the planned allocation ratio or a statistical plan for comparing the regimens. The safety listing includes a sixth group labeled Pre-treatment, with no intervention description in the registry record. The record does not clarify that group’s role, so it should not be assumed to be a randomized comparator.

A secondary outcome concerns ex vivo inhibition of HIV-1 infectivity in tissue biopsies for Groups 1, 2, and 3. The record lists 16 outcome measures overall but reports no analyses. It does not provide enough information to describe the full schedule of assessments or to infer how the different groups were intended to be compared.

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

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.

Population: In Groups 1-3, participants who have their biopsies collected at visit 2; in Groups 4-5, participants who receive infusion at visit 3

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Reporting Local Reactogenicity Signs and Symptoms, measured over Measured through 3 days after each infusion at months 0, 2, 3, 4 or 6 (infusion visits depending on which group participants are in).

The primary endpoint is the number of participants reporting local reactogenicity signs and symptoms. Reactogenicity refers to local signs or symptoms assessed after an infusion; the registry specifies that grading followed the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017]. For each symptom, the maximum grade observed during the stated observation window is presented.

The timeframe is through 3 days after each infusion at Months 0, 2, 3, 4, or 6, depending on the group’s infusion visits. The endpoint is therefore a count of participants meeting the reporting definition over a defined post-infusion period, rather than a continuous measure of symptom intensity or a time-to-event measure. The maximum-grade approach preserves the highest recorded severity for each symptom within that window; it does not describe how long a symptom lasted or how often it occurred.

Such an endpoint is used in an early-phase study to describe short-term local tolerability after administration and to characterize reported symptoms by severity. Its interpretation depends on the grading rules, observation window, and the way repeated infusions and symptoms are summarized. The registry record gives the endpoint definition but does not report its group-specific results. Therefore, no comparison of local reactogenicity counts or grades between regimens can be made from the information recorded.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is the primary endpoint?

The primary endpoint is a count of participants reporting local reactogenicity signs and symptoms. A count outcome records how many participants meet a defined event criterion. It is not itself a rate unless the observation time and denominator are explicitly incorporated, and it is not a continuous measure. Here, the registry specifies the symptom grading standard and a window through 3 days after each infusion. It also says that the maximum grade for each symptom over that period is presented.

General statistical explanation: when an outcome is reported as a count, interpretation should distinguish the number of participants with an event from the number of events. One participant can potentially have more than one sign or symptom, so a participant count and a symptom-event count answer different questions. The registry endpoint is explicitly framed as participants reporting symptoms, but the group-specific primary results are not reported in the registry record.

Why does the endpoint definition matter?

A grading standard makes severity categories more consistent, but the endpoint still depends on what was assessed and how observations were summarized. Using the maximum grade captures the highest recorded severity for each symptom in the stated window; it does not measure duration, repeated episodes, or symptom burden over time. The visit schedule also differs among groups, so the number and timing of post-infusion observation windows are not identical across regimens. The registry does not provide further details about missing symptom assessments or how repeated reports were handled in the primary outcome.

What can the safety counts show?

The adverse-event listing gives affected-participant counts and participants at risk separately for serious events and other events. These counts are descriptive. They allow a reader to see the reported counts within each listed group, but do not by themselves account for differences in group size, exposure schedule, or observation time. General statistical explanation: a direct comparison of event counts can be misleading when the groups differ in the amount of time participants were observed or in their opportunities to experience an event. A rate or model may be appropriate for some questions, but the registry does not report such an analysis for these safety results.

The record includes percentages for selected serious-event terms but does not provide their associated denominators or group assignments in the available listing. A percentage is interpretable only with a clear numerator, denominator, and definition of the event set. These terms therefore should be read as entries in the record, not as a basis for estimating or comparing regimen-specific risks.

What do randomization and masking contribute?

The record identifies the study as randomized and parallel, which means participants were assigned among concurrent groups according to a random process, as described at a broad level in the registry. Randomization can support fair comparisons by reducing systematic differences at baseline, but it does not guarantee identical groups, especially when groups are small. The registry does not report the randomization method, allocation concealment, or allocation ratio. It states that masking was none, so the study was unmasked. The record does not explain how knowledge of assigned regimen may have been managed during symptom reporting or assessment.

General statistical explanation: masking is one way to limit the influence of expectations on subjective assessments. A standardized grading scale can improve consistency, but it does not eliminate possible reporting or assessment effects when participants and assessors know the assigned regimen. The registry does not provide enough details to determine the extent of any such influence.

How should statistical uncertainty be understood?

A confidence interval is a range of estimates compatible with the observed data under a specified statistical method. It communicates uncertainty around an estimate; it is not a guarantee that the true value lies within the interval. No confidence intervals or inferential analyses for the primary endpoint are reported in the registry record, so the precision of a regimen comparison cannot be assessed. No significance test for the listed safety counts is reported either.

General statistical explanation: count outcomes can have more variability than a simple model assumes, particularly when participants differ in their underlying event tendency or when events cluster. Over-dispersion means observed variability exceeds the model’s assumed variability; ignoring it can make uncertainty appear too small. The registry does not report a count model, an over-dispersion assessment, or other modeling details, so it is not possible to say whether such methods were used.

The sample-size assumptions described for planning illustrations specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. For time-to-event tables, the planning quantity is the total number of events; for other outcomes, it is participants per arm. These are planning illustrations, not observed power. The registry does not report that these assumptions formed the trial’s original design or provide the trial’s own sample-size justification.

Why do the different regimens complicate a contrast?

The groups vary in product, dose, and schedule. A contrast between two groups would therefore compare the complete regimens assigned to those groups, not necessarily isolate a single component. The record does not specify a single control arm for the primary endpoint or report a statistical plan defining which group contrasts were intended. No adjusted or unadjusted results are reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures, including the primary local reactogenicity endpoint and a secondary outcome concerning ex vivo inhibition of HIV-1 infectivity in tissue biopsies for Groups 1, 2, and 3. Considering multiple outcomes, symptoms, grades, time points, and possible group contrasts can create multiplicity: the more questions tested, the greater the chance that some apparently notable result arises by chance. General statistical explanation: multiplicity can be handled by prespecifying a limited set of primary comparisons, adjusting significance thresholds, or emphasizing estimation and uncertainty rather than treating every test as confirmatory.

The registry record reports zero analyses. It does not describe a multiplicity adjustment, a hierarchy among outcomes, or a prespecified set of primary comparisons. It also does not report a statistical analysis plan. The primary endpoint is described as having several categories or time points and is not reduced to one comparison in the record. Therefore, there is no reported inferential result on which to assess multiplicity or determine how the different possible comparisons were handled.

Missing-data methods and analysis populations are not reported in the registry record. The record does not state how participants with incomplete symptom assessments, missed infusions, withdrawal, or unavailable safety follow-up were handled. It does not identify an intention-to-treat, per-protocol, or other analysis population for the primary endpoint. Although the safety listing gives participants at risk in each group, those figures alone do not describe missing observations or define the analysis population for every outcome.

These omissions limit reproducibility and interpretation. Without the analysis population, missing-data rules, and prespecified comparison strategy, readers cannot determine whether the reported counts represent all randomized participants, participants who received an intervention, or another defined set. None of these details should be inferred from the group labels or the fact that the study was randomized.

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 (14.3%), transient ischaemic attack (14.3%), appendicitis (10.0%), blood loss anaemia (4.3%), adenomyosis (4.3%).

The safety listing separates serious events from other events and reports the number of affected participants alongside the number at risk in each group. For serious events, the affected-participant counts are 0 in Group 1, 1 in Group 2, 1 in Group 3, 0 in Group 4, 1 in Group 5, and 0 in Group 6. The corresponding participants-at-risk counts are 23, 23, 7, 16, 10, and 1. For other events, the affected-participant counts are 22, 18, 7, 7, 3, and 1, with corresponding at-risk counts of 23, 23, 7, 16, 10, and 1.

These are counts, not statistical comparisons. The groups differ in size and regimen, and the record does not provide exposure-adjusted rates, confidence intervals, or tests for differences. The sixth group is labeled Pre-treatment, but its role is not described further in the registry record. The listed serious-event terms and percentages do not include their associated denominators or group assignments in the available record. They should not be interpreted as regimen-specific rates or as evidence of a causal relationship.

The primary endpoint is specifically local reactogenicity, whereas these safety counts are presented in the adverse-event listing. The two should not be conflated. The registry record does not report the primary endpoint results by group, and the general safety counts cannot substitute for those results.

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

The record establishes the study’s broad design and the intervention schedules: it was a randomized, unmasked, parallel Phase 1 study of VRC01 and VRC01LS in healthy, HIV-uninfected adults. It also defines the primary endpoint as the number of participants reporting local reactogenicity signs and symptoms, graded by maximum severity through 3 days after an infusion. These details describe what the study set out to evaluate and how the primary outcome was framed.

The record also gives descriptive serious-event and other-event counts for six listed groups. Those values document what appears in the registry’s safety listing. They do not, without a reported statistical analysis and fuller exposure and follow-up information, establish whether one regimen differs from another. Differences in the counts may reflect group size, regimen, observation, or chance; the record does not allow those explanations to be separated.

The record does not report group-specific results for the primary local reactogenicity endpoint, statistical comparisons, confidence intervals, or a statistical analysis plan. It therefore cannot show the magnitude or precision of any difference in the primary outcome. It also cannot establish that a regimen is effective against HIV: the population was HIV-uninfected adults, and the stated primary endpoint concerns local reactogenicity rather than prevention or treatment of HIV infection. The secondary outcome description concerns ex vivo inhibition in tissue biopsies for specified groups, but results for that outcome are not reported in the record.

Accordingly, the registry information supports a description of the trial design, outcome definition, and listed safety counts, but not a conclusion about comparative efficacy, definitive safety differences, or the clinical importance of any regimen. A completed study status does not itself provide the missing results or analysis details.

13. Why This Trial Matters Statistically

This trial is statistically notable because it compares several regimens that differ in product, dose, and schedule within an early-phase study. Such a design can provide descriptive information across exposure patterns, but interpretation of a contrast depends on the particular groups being compared. A difference between two complete regimens would not automatically identify whether product, dose, or schedule accounted for it.

The primary outcome is a graded symptom measure summarized as participant counts, with the maximum grade recorded for each symptom during a defined post-infusion window. This illustrates a common challenge in safety analysis: a simple count can conceal differences in severity, symptom type, timing, and repeated experience. The registry record describes the grading approach, but does not report the primary outcome results needed to assess those dimensions by group.

The safety listing also demonstrates why denominators and context matter. Counts of affected participants are shown with participants at risk, while group sizes and schedules vary. Descriptive counts should not be mistaken for inferential comparisons, and percentages for event terms require clear denominators and group attribution. Those details are not reported for the listed serious-event terms.

Finally, the record lists multiple outcome measures but no analyses. This makes the distinction between a planned endpoint and a reported result especially important. A well-defined endpoint is not itself evidence of an observed effect, and a completed status does not supply uncertainty estimates or explain how multiple outcomes, missing observations, or analysis populations were handled. Statistically, the record is most useful for understanding the design and the limits of what can be concluded from the registered results.

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 main limitation for interpreting the primary question is that the registry record defines the local reactogenicity endpoint but does not report its results by group. No counts by symptom or grade, group comparison, confidence interval, or statistical test for that endpoint appears in the record. The listed adverse-event counts cannot be substituted for the missing primary endpoint results because the record does not identify them as the primary local reactogenicity outcome.

The regimens vary in antibody, dose, and schedule, and the record does not specify a single control regimen for the primary endpoint. This makes any simple treatment-versus-control framing inappropriate. The safety listing includes Group 6, labeled Pre-treatment, but the group’s role and regimen are not reported. The record also does not give the allocation ratio or further details of randomization.

Important analysis details are absent: no statistical analysis plan, analysis populations, missing-data methods, multiplicity approach, or interim-analysis information is reported in the registry record. The record does not provide exposure-adjusted safety analyses or detail the observation time represented by the safety counts. For the serious-event terms, the listed percentages lack accompanying denominators and group attribution in the available information.

The sample-size assumptions describe planning illustrations, not the trial’s own design justification, and the registry does not report the original sample-size rationale. The completed status and enrollment listing do not resolve these gaps. Overall, the registry supports description of the study setup and the reported safety counts, but not a precise or comparative assessment of the primary endpoint.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluating the Safety, Pharmacokinetics, and Anti-Viral Activity of VRC01 and VRC01LS in the Serum and Mucosa of Healthy, HIV-Uninfected Adults — NCT02797171.
• Registry record last updated 2024-03-20; status last verified 2022-08.
• Results first posted 2021-01-08.
• 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

This completed, randomized, unmasked, parallel Phase 1 study evaluated VRC01 and VRC01LS in healthy, HIV-uninfected adults. The registry lists an enrollment of 80 and five intervention groups with different products, doses, and schedules. A sixth group is listed as Pre-treatment in the safety results, but its role is not described.

The primary endpoint counts participants reporting local reactogenicity signs and symptoms, graded by maximum severity through 3 days after an infusion. The registry record does not report the group-specific primary endpoint results or any statistical analyses. It does list serious-event and other-event counts by group, along with selected serious-event terms and percentages, but those descriptive entries do not establish comparative risks.

Analysis populations, missing-data methods, multiplicity handling, and the statistical plan are not reported in the registry record. The available information supports an account of the trial design and registered safety data, but not a conclusion about comparative efficacy or a precise difference in local reactogenicity.