Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion in Healthy, HIV-uninfected Adult Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion in Healthy, HIV-uninfected Adult Participants (NCT03928821), 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

This is a safety-focused early-phase question, not a direct test of clinical benefit. The registry also describes pharmacokinetic and antiviral-activity outcomes, including serum concentrations and neutralizing responses, but the posted information does not provide their results. The primary endpoint is a participant count rather than a measure of antibody concentration or antiviral activity. The record specifies assessment through 3 days after each vaccine dose at T1-T3: Day 0, and at T4: Days 0, 112. The maximum grade for each symptom over the stated timeframe is the severity summary. The registry does not report a primary endpoint result or an inferential comparison among the groups.

3. Trial Design

The registry describes NCT03928821 as a completed Phase 1, randomized, open-label, parallel trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The listed enrollment is 27. Participants were assigned among groups receiving different combinations of monoclonal antibodies by intravenous infusion. Because masking is listed as none, the study was not masked according to the registry record. Details of how the random sequence was generated, whether allocation was concealed, or how assignment was implemented are not reported in the registry record.

The first group received PGT121 followed by VRC07-523LS at Day 0. The second received PGDM1400 followed by VRC07-523LS at Day 0. The third received 10-1074 followed by VRC07-523LS at Day 0. The fourth received PGDM1400, PGT121, and VRC07-523LS sequentially at Day 0 and Month 4. These are active-combination groups; a placebo or untreated comparator is not described.

The primary outcome concerns local pain and/or tenderness, graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, dated July 2017. The assessment timeframe is through 3 days after each dose, with timing described as T1-T3: Day 0, and T4: Days 0, 112. The registry lists 15 outcome measures, with secondary measures covering antibody concentrations and responses in TZM-bl cells. The exact statistical analysis plan, planned comparisons, sample-size justification, and procedures for handling departures from the schedule are not reported in the registry record.

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.

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 T1-T3: Day 0 and T4: Days 0, 112.

The primary endpoint counts participants reporting local pain and/or tenderness. The registry describes the maximum grade observed for each symptom over the assessment timeframe, using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1. The timeframe is through 3 days after each vaccine dose at T1-T3: Day 0 and T4: Days 0, 112.

A participant count is an interpretable way to describe how often a specified local symptom was reported in each group. Grading adds information about the most severe recorded experience during the defined period, rather than treating all reports as equivalent. As a general statistical point, presenting both the occurrence of a symptom and its maximum grade can help distinguish how many participants reported it from how severe their recorded symptoms became. The endpoint is still limited to the symptoms named in its definition and the stated observation window; it does not by itself summarize every aspect of safety or tolerability.

The registry record does not report the primary endpoint counts, grade distribution, or an inferential comparison. It also does not provide details about how missing symptom assessments were handled. Consequently, the endpoint definition clarifies what was intended to be measured, but the posted record does not support conclusions about the observed frequency or severity of pain or tenderness in these groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry lists a randomized, open-label, parallel design. In a randomized trial, assignment by chance is intended to make comparison groups less dependent on participant or investigator choice. That general rationale does not reveal how randomization was carried out in this trial: sequence generation, allocation concealment, and implementation details are not reported in the registry record. Open-label means masking is listed as none. As a general statistical consideration, knowledge of assignment can influence reporting or assessment of subjective outcomes such as symptoms, even when a grading framework is specified. The record does not describe additional steps used to address that possibility.

What does a participant count describe?

The primary endpoint is a count of participants reporting pain and/or tenderness, with maximum severity grade described over the specified period. A count answers how many participants met the endpoint definition in a group. It is not the same as a count of symptom episodes, because the endpoint is explicitly framed around participants. A grade provides an ordered description of severity; it does not make the distance between adjacent grades quantitatively equal. These are general properties of categorical and ordinal outcomes. The registry record does not post the primary counts or grade distributions, so those features cannot be assessed for this trial from the posted results.

How should comparisons be read?

For a binary outcome such as whether a participant reported a symptom, analysts may describe group-specific counts and proportions, then estimate a contrast such as a difference in proportions or a relative measure. A confidence interval generally describes the range of values compatible with the data and the chosen statistical procedure; it communicates uncertainty rather than guaranteeing that the true value lies in a particular interval. This is general explanation, not a description of an analysis reported for this trial. The registry record does not provide the primary comparison, an estimate, a confidence interval, or a p-value. No unadjusted re-calculation is available to interpret because the primary endpoint results are not posted.

What statistical plan is documented?

The registry lists 15 outcome measures and 0 analyses. The specific statistical methods for the primary outcome, secondary outcomes, and safety summaries are not reported in the registry record. In particular, the record does not report whether comparisons were planned as exploratory or confirmatory, what model or test would be used, whether adjustments for baseline characteristics were intended, or how estimates and uncertainty would be presented. These details should not be inferred from the study’s phase or design labels.

The record contains a general planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; its target effect is a stated fraction of the observed effect. Such an illustration is a planning calculation, not observed power and not evidence that the trial was designed using those assumptions. The registry does not report the trial’s own sample-size justification. The primary outcome is marked as having several categories or time points and is not reduced to one comparison, so the planning illustration should not be mistaken for a trial-specific analysis of that endpoint.

Why do small event counts matter?

For binary outcomes, uncertainty is often substantial when event counts and group sizes are limited. A difference in counts may appear noticeable while still being imprecisely estimated. Confidence intervals, if reported, would help show that uncertainty; they are not present for the primary endpoint in the registry record. General statistical methods for sparse outcomes may include exact or carefully chosen model-based procedures, but the record does not state which, if any, were used. The posted serious-event information is best read as group-level descriptive counts rather than as a formal test or comparative estimate.

Over-dispersion is a concern for count outcomes when variability exceeds what a selected model expects. It matters when the model’s uncertainty estimates rely on a variance assumption that does not fit the observed data. The primary endpoint is specified as a count of participants with symptoms, not a repeated-event rate, and the registry does not report a model or an over-dispersion assessment. Consequently, no claim about over-dispersion or a correction for it can be made for this trial.

Overall, the design labels and endpoint definition identify the question the investigators intended to address. The posted results available in the registry record do not include the primary outcome analysis needed to quantify that question, and the exact analytic procedures remain unreported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the primary local-reactogenicity measure and secondary outcomes concerning serum concentrations and TZM-bl cell responses. When a study examines several outcomes, time points, or group contrasts, the chance of at least one apparently unusual result can increase. This is a general statistical issue called multiplicity. Methods such as prespecifying a primary contrast, organizing outcomes into a hierarchy, or adjusting inference can address different multiplicity concerns, but the registry record does not report a multiplicity strategy for this trial.

The primary outcome is described as having several categories or time points and is not reduced to one comparison. The record does not specify which time point or contrast, if any, would be the principal inferential test, nor does it report whether secondary outcomes were intended to be descriptive or subjected to formal testing. No p-values or confidence intervals for these outcomes are reported in the registry record.

Missing-data procedures and analysis populations are also not reported in the registry record. It is not stated how incomplete symptom diaries or missed assessments were handled, whether participants were analyzed according to randomized assignment, or whether any analyses were limited to participants who received all scheduled administrations. Some secondary outcome descriptions explicitly refer to participants who received all scheduled product administrations, while other listed measures refer to all participants; the record does not provide the detailed population definitions or handling rules behind those descriptions.

These omissions matter because the interpretation of a count depends on who was included and how unavailable assessments were treated. Without those details, readers cannot assess whether the posted summaries represent every randomized participant, a subset with observed data, or another analysis population. No missingness pattern or method should be inferred.

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 (16.7%), respiratory distress (16.7%).

The registry safety information separates serious adverse events from other adverse events and gives, for each group, the number at risk and the number affected. For serious adverse events, the entries are 0 of 6 in the PGT121 plus VRC07-523LS group, 1 of 6 in the PGDM1400 plus VRC07-523LS group, 0 of 6 in the 10-1074 plus VRC07-523LS group, and 0 of 9 in the PGDM1400 plus PGT121 plus VRC07-523LS group. The corresponding death counts are 0, 1, 0, and 0.

The other-event counts are 5 of 6, 6 of 6, 4 of 6, and 4 of 9 in the same group order. These are the registry’s separate other-event entries and should not be added to the serious-event counts. The listed top serious-event terms are “Any Event in SOC” and “Respiratory distress,” each reported as 16.7%. The record does not provide enough detail to assign those terms to a particular group or infer a relationship to an antibody.

These counts are descriptive, not comparative estimates. They do not establish causation, and the registry record does not report an inferential analysis of the serious-event differences. Because the group denominators are limited, absence of a recorded serious event in a group should not be interpreted as proof that the risk is zero.

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

The posted registry information establishes that the trial compared several randomized antibody combinations in healthy, HIV-uninfected adults and specified local pain and/or tenderness as its primary endpoint. It also provides group-level serious and other adverse-event counts. Those details can help readers understand the study’s scope and the safety information entered in the record.

However, the primary endpoint results are not reported in the registry record. There are no posted counts or severity grades for the primary symptoms, and no comparative effect estimate, confidence interval, or p-value. The record therefore does not show the observed frequency or severity of local pain or tenderness across the groups. Nor does it establish whether any differences among groups were statistically distinguishable from random variation.

The safety counts likewise do not establish that an antibody caused an event or that a combination is safer or less safe than another. The presence of a death count in one group is a registry entry, not evidence by itself of causation. The posted information does not include the circumstances, attribution, or a comparative analysis needed to interpret that entry beyond its recorded count.

More generally, a randomized design can support comparisons when results and analytic methods are reported, but the design label alone is not a result. This trial’s Phase 1 setting, open-label status, limited enrollment, and combination-specific dosing schedule are important context for interpreting any future or separately reported findings. The registry record does not provide a basis for conclusions about clinical effectiveness, population-wide risks, or the relative merits of the antibody combinations.

The appropriate reading is therefore narrow: the record describes what was studied, how the primary endpoint was defined, and selected safety counts. It does not provide the primary results needed to answer whether symptom occurrence or severity differed among the groups.

13. Why This Trial Matters Statistically

This trial illustrates how a clinical question and an analysis-ready result are not the same thing. The registry defines a concrete safety endpoint: participant reports of local pain and/or tenderness, with maximum severity grade assessed over a specified period. That definition identifies the outcome of interest, but without the observed counts and grades it cannot answer how frequently symptoms occurred or how their severity varied across combinations.

The design also highlights the importance of distinguishing a randomized comparison from a randomized conclusion. Random assignment is a design feature; estimating a contrast requires posted results and a specified analytic approach. The registry identifies four active-combination groups and an open-label parallel structure, yet the primary endpoint is not presented as one comparison and no primary analysis is reported. Statistical interpretation must therefore stop short of ranking the combinations or claiming evidence for a difference.

Finally, the safety record demonstrates why event counts need context. Group-specific denominators, serious-event counts, other-event counts, and death counts are separate pieces of information. They should not be collapsed into an invented total or interpreted as causal effects. A small early-phase study can describe observed events, while still leaving substantial uncertainty about comparative risks. The record’s missing primary results and unreported analysis plan are central to that uncertainty, not minor technical details.

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 trial-specific limitation in the registry record is the absence of reported primary endpoint results. The endpoint definition is detailed, but participant counts and maximum grades for pain and/or tenderness are not reported in the registry record. The record also does not provide an inferential comparison, effect estimate, confidence interval, or p-value for that endpoint.

The listed enrollment is 27, and the safety entries give group-specific denominators of 6, 6, 6, and 9. These limited group counts constrain how precisely event frequencies can be characterized. The record is open-label, and local symptoms rely on participant reporting; masking is listed as none. The registry does not describe procedures intended to reduce reporting or assessment bias.

The intervention schedules differ: three groups are described as receiving two antibodies sequentially at Day 0, while the fourth receives three antibodies at Day 0 and Month 4. This means the groups differ in both combination and schedule. The record does not report a design or analysis that separates the contribution of each antibody from the combination and timing differences.

Further limitations include the absence of reported randomization procedures, a trial-specific sample-size justification, an analysis plan, missing-data methods, and detailed analysis-population definitions. The registry lists 15 outcome measures but does not report a multiplicity strategy. Safety entries do not include event attribution details in the available information. These limitations do not invalidate the registry descriptions; they restrict the conclusions that can be drawn from them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion in Healthy, HIV-uninfected Adult Participants — NCT03928821.
• Registry record last updated 2022-07-11; status last verified 2022-06.
• Results first posted 2022-07-11.
• 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

NCT03928821 is a completed, randomized, open-label, parallel Phase 1 trial sponsored by NIAID. It enrolled 27 healthy, HIV-uninfected adult participants and evaluated intravenous combinations of PGT121, PGDM1400, 10-1074, and VRC07-523LS.

The primary endpoint was the number of participants reporting local pain and/or tenderness, with maximum severity graded over the stated assessment periods. Primary endpoint results and statistical analyses are not reported in the registry record. The record lists serious adverse event counts of 0, 1, 0, and 0 across the four groups, and death counts of 0, 1, 0, and 0. These are descriptive entries and do not establish causation or comparative risk.

The registry lists secondary pharmacokinetic and antiviral-activity outcomes, but their results are not reported in the information available for this analysis. Details of the statistical plan, missing-data handling, and multiplicity procedures are also not reported in the registry record.