Study in Healthy Volunteers Evaluating Safety and Pharmacokinetics of Zika Virus Immune Globulin (ZIKV-IG): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study in Healthy Volunteers Evaluating Safety and Pharmacokinetics of Zika Virus Immune Globulin (ZIKV-IG) (NCT03624946), a randomized phase 1 study. The primary outcome is Number of Subjects With Adverse Events..

2. Clinical Question

The study was designed to evaluate safety and pharmacokinetics in healthy volunteers, rather than to measure prevention or treatment of Zika virus infection in people with the disease. The registry describes Zika Virus Immune Globulin as under development and identifies the absence of licensed therapeutics as the context for its investigation. Those statements explain the study rationale; they are not findings from the trial.

The central clinical question is therefore about tolerability and how the investigational product behaves in the body after administration. The primary outcome concerns adverse events, while the listed secondary outcomes cover maximum concentration, time to maximum concentration, area under the concentration curve, clearance, half-life, and volume of distribution. The registry record does not report results for those pharmacokinetic measures in the registry record for this analysis.

3. Trial Design

This was a Phase 1, randomized, quadruple-masked, parallel-group study. The registry lists enrollment as 30 and identifies healthy volunteers as the study population. The record describes two interventions: Zika Virus Immune Globulin and placebo. Each arm description specifies one intravenous administration of 50 mL over 33 minutes. The placebo is described as saline solution.

The study is identified as a first-in-human evaluation. Its stated aims were to assess safety and pharmacokinetics, meaning the absorption, metabolism, and excretion of the investigational product. The listed secondary outcomes make that aim more specific by naming pharmacokinetic measures, including maximum concentration, time to maximum concentration, area under the curve, clearance, half-life, and volume of distribution.

The primary outcome is the number of participants with adverse events by severity, assessed through Day 85. The defined safety population includes participants who received any amount of study treatment, whether Zika Virus Immune Globulin or placebo. The posted adverse-event counts are presented by study arm, with serious adverse events and other adverse events distinguished.

The registry lists the study as completed. Its recorded start date is 2018-06-27, and its primary completion date is 2019-03-06. These are registry dates, not a description of the timing of individual participants’ visits. The record does not report the schedule of pharmacokinetic sampling, the detailed visit schedule, or the planned duration of follow-up beyond the primary outcome timeframe.

Randomization indicates that assignment to study groups was intended to use chance, while masking indicates that knowledge of assignments was restricted among the groups specified by the study’s masking designation. The registry record does not specify which four parties were masked or describe the randomization procedure. A parallel design means participants were assigned to one study group rather than receiving both interventions in sequence; further design details 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:

Analysis population for the primary outcome, as defined in the registry: Safety population includes all subjects who received any amount of study treatment (ZIKV-IG or placebo).

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 Subjects With Adverse Events., measured over Up to Day 85.

The primary endpoint counts participants who experienced adverse events, with events classified by severity, through Day 85. It is a safety outcome: it describes whether participants in the defined safety population had reported adverse events during the specified period. The registry defines that population as all subjects who received any amount of study treatment.

Counting participants with events is useful in an early-phase study because it gives a direct summary of how many people experienced events during exposure and follow-up. Separating events by severity can distinguish serious events from other events and help characterize the safety observations. The registry’s outcome description says “by severity,” but the record does not provide a complete severity breakdown in the registry record. The posted adverse-event figures distinguish serious events and other adverse events.

These counts should be read as participant counts, not as a total number of event episodes. A participant could potentially experience more than one event, but the posted primary outcome is defined in terms of subjects with events. The record does not state whether participants could appear in more than one severity category, nor does it provide event-level descriptions for the other adverse events.

Safety outcomes are appropriate for a first-in-human evaluation, where observation of adverse events is an important part of characterizing a product under study. However, this endpoint alone does not establish a product’s overall safety profile. Interpretation depends on the population, exposure, follow-up, event definitions, and completeness of reporting. Several of those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, quadruple-masked, parallel-group design. Randomization is generally used to reduce systematic differences between groups at assignment by using chance to allocate participants. It does not guarantee that groups will be identical, especially in a small study. The registry record does not describe the sequence-generation method, allocation concealment, or the parties included in the quadruple-masking designation. Those details are not reported in the registry record.

What does the primary outcome count?

The primary outcome is the number of subjects with adverse events, classified by severity, through Day 85. The safety population is defined as all subjects who received any amount of study treatment. The posted results distinguish serious adverse events from other adverse events. These are counts of participants, rather than a modeled rate or a count of every event episode. General statistical principle: the unit being counted matters. Participant-level counts answer how many people experienced an event, whereas episode counts answer how many events occurred; the two summaries need not be the same.

The registry entries available for this analysis do not include a single comparison estimate for the primary outcome. The registry notes that the outcome has several categories or time points and was not reduced to one comparison. Consequently, there is no reported effect estimate, confidence interval, or p-value for a unified primary contrast. The reported counts can be described directly, but they do not support an inferential claim about a difference between the groups without further analysis and its assumptions.

Why is a confidence interval useful?

General statistical principle: an estimate summarizes the observed data, while a confidence interval conveys uncertainty around that estimate under a specified statistical procedure. A wider interval generally indicates less precision than a narrower one. For event counts, precision depends on the amount of information and the analysis used. No confidence interval is reported for the adverse-event figures in the registry record, so their statistical precision cannot be assessed from an interval in these results.

A p-value, when reported, describes how compatible the data are with a specified null hypothesis under the assumptions of the test. It does not measure the probability that a treatment works, and it does not express the size or practical importance of an effect. No p-value for the primary outcome comparison is reported in the registry record. The absence of such a result should not be replaced by a calculation from the posted counts, because the registry does not specify a single comparison or statistical procedure for this outcome.

What can masking and parallel assignment contribute?

General statistical principle: masking can reduce the influence of expectations on care, event reporting, or outcome assessment, depending on who is masked and how the study is conducted. A parallel-group design avoids exposing the same participant to both interventions in sequence, so group comparisons are between participants assigned to different arms. The registry’s labels identify masking and design, but the practical implementation is not described in the registry record. It is therefore not possible to assess masking success or the details of assignment from these registry entries alone.

The primary outcome includes adverse events, which may depend in part on how events are elicited, classified, and attributed. The record does not report the event-collection procedures, definitions, adjudication process, or rules for assigning severity. It also does not report how missing safety assessments were handled. These details affect how completely and consistently participant events can be captured, and are important when interpreting descriptive counts.

How should planning calculations be understood?

The registry’s planning description says that sample-size illustrations use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such calculations are hypothetical planning illustrations, not observed results and not evidence that the study had a particular probability of detecting an effect. The record does not report the trial’s own sample-size justification or a planned effect size. No numerical planning outputs are reported in the registry record, so no sample-size requirement can be stated.

General statistical principle: power is a design property calculated under assumptions about the outcome, effect size, variability, analysis, and significance threshold. It is not a measure of whether the observed result is reliable. A calculation based on an observed effect is especially dependent on that effect estimate and should not be interpreted as “observed power.” The registry record does not report an observed-power analysis.

The outcome is binary at the participant level when framed as whether a person had an event, but it is also described across severity categories and time points. A single binary comparison would discard some of that structure. The registry explicitly does not reduce this primary outcome to one comparison, and the registry entries do not identify a model that jointly analyzes categories or repeated observations. No assumptions about such a model should be inferred.

Pharmacokinetic outcomes are listed separately, including maximum concentration, time to maximum concentration, area under the curve, clearance, half-life, and volume of distribution. General statistical principle: pharmacokinetic summaries describe different features of concentration over time, and their interpretation depends on sampling and analysis methods. The registry record does not report numerical results, sampling details, transformations, or estimation procedures for these outcomes in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is described as adverse events by severity through Day 85, and the registry indicates that it contains several categories or time points rather than one reduced comparison. The record does not report a multiplicity-adjustment procedure or explain how inferential claims across categories or time points would be controlled. Since no single primary comparison is reported, the posted counts should be treated as descriptive rather than as a set of confirmatory tests.

The listed secondary outcomes include multiple pharmacokinetic measures: maximum concentration, time to maximum concentration, area under the curve up to the last quantifiable concentration, area under the curve extrapolated to infinity, clearance, half-life, and volume of distribution. The registry record does not report a testing hierarchy, multiplicity procedure, or inferential results for these measures in the registry record. It is therefore not possible to determine whether or how multiplicity was addressed for secondary analyses.

Missing-data handling is not reported in the registry record. The safety population is defined as all subjects who received any amount of study treatment, but the record does not describe how participants with incomplete follow-up, missing assessments, or unavailable event information were handled. It also does not report the completeness of outcome collection through Day 85. The definition of the population does not by itself explain how missing observations were treated.

The record does not specify an analysis plan, interim analyses, or a method for handling participants who discontinued or deviated from the planned treatment. These details should not be assumed. Without them, the posted counts can be read as the adverse-event figures recorded for each arm, but the extent to which they represent complete follow-up or a prespecified analysis cannot be established from the registry record.

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 non-serious adverse event terms

The serious adverse-event figures are 0 of 19 participants in the Zika Virus Immune Globulin group and 0 of 11 participants in the placebo group. These are the reported participant counts for serious events in the safety population. They indicate that no serious adverse events are listed for either group in the posted results. They do not demonstrate that the risk is zero or rule out events that could occur in a broader population or with more observation.

The other-adverse-event figures are 12 of 19 participants in the Zika Virus Immune Globulin group and 8 of 11 participants in the placebo group. They are counts of participants with other adverse events, not counts of every event episode. The record does not name those events or describe their severity distribution in the registry record. It also does not provide uncertainty intervals or a formal statistical comparison for these counts.

Adverse-event counts are best read alongside the study population, exposure, and follow-up. Here, the population is healthy volunteers, the interventions are single intravenous doses, and the primary outcome timeframe is through Day 85. The registry record does not report detailed collection procedures or completeness of follow-up. These limitations mean that the figures describe what was recorded in this study, rather than providing a complete characterization of safety across other settings or populations.

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

The posted results document adverse-event counts for a randomized, masked, parallel-group study in healthy volunteers. For serious adverse events, the registry reports 0 of 19 participants in the Zika Virus Immune Globulin group and 0 of 11 participants in the placebo group. For other adverse events, it reports 12 of 19 and 8 of 11 participants, respectively. These are descriptive observations from the safety population through the stated primary-outcome timeframe.

The counts do not establish that one group had a higher or lower underlying risk. No single inferential comparison, confidence interval, or p-value is reported for the primary outcome. The categories and time points were not reduced to one comparison, so it would be inappropriate to present a simple statistical conclusion based only on the raw counts. The registry entries also do not include enough detail to assess event definitions, completeness of reporting, or missing safety observations.

The study’s stated objectives include pharmacokinetic evaluation, but numerical results for the listed pharmacokinetic outcomes are not reported in the registry record. The adverse-event counts therefore cannot answer questions about concentration or disposition of the product. Likewise, the study was conducted in healthy volunteers and the primary endpoint is a safety measure. The results do not establish whether Zika Virus Immune Globulin prevents or treats Zika virus infection.

General statistical principle: a small early-phase study is generally intended to characterize observations and inform further investigation, not to precisely quantify rare outcomes or establish effects across broad populations. The registry does not report a sample-size justification, and no numerical confidence intervals are available for these safety counts. The absence of serious events in the posted figures is a limited observation, not proof that serious events cannot occur.

Overall, the record supports a careful descriptive reading: it reports adverse events in both groups, no serious events in either group, and no single inferential primary comparison. Any broader interpretation would require additional information about the study conduct, analysis, and outcome reporting that is not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable as a first-in-human evaluation with safety and pharmacokinetic aims. Early-phase studies often emphasize careful description of observed events and product disposition rather than a definitive comparison of clinical benefit. In this record, the primary endpoint counts participants with adverse events by severity, while the secondary outcomes cover several pharmacokinetic characteristics.

The design labels—randomized, quadruple-masked, and parallel—are relevant to how comparisons might be interpreted. Randomization can help limit systematic allocation differences, and masking can reduce some sources of assessment or reporting bias. These design features do not remove uncertainty, and the registry record does not describe their implementation in enough detail to evaluate it. The primary results also do not include a single comparison estimate or uncertainty interval.

The study illustrates why endpoint structure matters. A safety outcome spanning severity categories and time points may not be adequately represented by one summary comparison. The registry notes that the primary outcome was not reduced to one comparison. Reporting the observed group counts preserves a direct account of the recorded events, but without a defined inferential analysis it does not quantify a comparative effect.

The registry’s planning description distinguishes hypothetical sample-size illustrations from trial results. General statistical principle: planning calculations rely on assumptions and are not observed evidence or a substitute for uncertainty intervals around actual results. The registry entries do not include numerical planning outputs or the trial’s own sample-size justification. This distinction is particularly important when interpreting an early-phase study whose posted safety findings are descriptive.

For clinical researchers and biostatisticians, the central lesson is to keep the scope of interpretation aligned with the estimand and reporting. These data describe adverse-event counts among healthy volunteers receiving a single dose, with no reported single inferential primary comparison. They do not, on their own, quantify uncommon risks, establish comparative safety, or answer efficacy questions.

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 registry record offers limited detail for interpreting the primary safety outcome. It reports participant counts for serious and other adverse events, but the registry entries do not name the other events, give a complete severity breakdown, describe event definitions, or explain how events were assessed. The record also does not report the completeness of follow-up through Day 85 or how missing safety observations were handled.

Although the design is labeled randomized, quadruple-masked, and parallel, the randomization procedure and the identities of the masked parties are not reported in the registry record. The record does not describe allocation concealment, treatment adherence, participant discontinuations, or protocol deviations. These omissions limit assessment of how the planned design was implemented.

The primary outcome includes several categories or time points and is not reduced to one comparison. The record does not report an inferential analysis, effect estimate, confidence interval, or p-value for a unified primary contrast. It also does not state how multiplicity was addressed. Consequently, the posted counts can be summarized, but they do not support a precise estimate of a between-group difference.

The study population was healthy volunteers, and the intervention was a single intravenous dose. This limits how directly the observations can be applied to other populations, settings, or treatment regimens. The primary endpoint is about adverse events, not prevention or treatment of Zika virus infection. Numerical results for the listed pharmacokinetic outcomes are not reported in the registry record, so those objectives cannot be evaluated from these results.

The record lists enrollment as 30 but does not report the trial’s own sample-size justification or a detailed statistical analysis plan. It also does not report interim analyses. These limitations are specific to what is documented and should not be filled in by assumptions about common Phase 1 practice.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study in Healthy Volunteers Evaluating Safety and Pharmacokinetics of Zika Virus Immune Globulin (ZIKV-IG) — NCT03624946.
• Registry record last updated 2024-03-18; status last verified 2024-03.
• Results first posted 2020-07-13.
• 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

The registry record describes a completed Phase 1, randomized, quadruple-masked, parallel-group study of Zika Virus Immune Globulin in healthy volunteers. It lists enrollment as 30 and identifies Zika virus infection and Zika virus disease as conditions of interest. The recorded study start date is 2018-06-27, and the primary completion date is 2019-03-06.

Participants received a single intravenous dose of 50 mL Zika Virus Immune Globulin or a single intravenous dose of 50 mL placebo, described as saline solution; each was administered over 33 minutes. The primary outcome counts participants with adverse events by severity through Day 85. In the posted safety figures, serious adverse events were reported for 0 of 19 participants receiving Zika Virus Immune Globulin and 0 of 11 receiving placebo. Other adverse events were reported for 12 of 19 and 8 of 11 participants, respectively.

The record also lists pharmacokinetic secondary outcomes, but numerical results for those outcomes are not reported in the registry record. The primary safety outcome was not reduced to one comparison, and the registry record does not report a single inferential treatment comparison.