A Study to Evaluate the Safety and Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Melrilimab (GSK3772847) in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety and Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Melrilimab (GSK3772847) in Healthy Participants (NCT04366349), a randomized phase 1 study. The primary outcome is Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

The registry describes NCT04366349 as a Phase 1, randomized, double-blind study of single ascending doses of subcutaneous melrilimab in healthy participants. Its official title identifies safety, tolerability, pharmacokinetics and pharmacodynamics as study objectives. The study also aimed to assess the bioavailability of the subcutaneous formulation and injection-site tolerability.

The intervention groups received a single dose of melrilimab at 70 mg or 140 mg, or a single dose of placebo. The study description places the 70 mg dose in Cohort 1 and the 140 mg dose in Cohorts 2, 3 and 4. Cohort 3 consisted of Japanese participants, and Cohort 4 consisted of Chinese participants. The injection site could be the upper arm, abdomen or thigh for Cohorts 1 and 2; Cohorts 3 and 4 received injections in the upper arm only.

The registry reports enrollment of 65 and lists the study as completed. It gives a start date of 2020-07-21 and a primary completion date of 2020-12-21. The brief description estimates the total study duration as up to 89 days. The primary adverse-event timeframe is through Day 85.

The posted safety results retain six groups, separating the two placebo cohort groupings and the 70 mg and 140 mg groups, including the Japanese and Chinese cohorts. That structure matters for interpretation: the counts describe specific groups and are not presented as one pooled comparison. Further details on allocation procedures, stratification, or the rationale for the cohort sizes 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.

Before assignment: A total of 65 participants were enrolled in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population consisted of all randomized participants who took at least 1 dose of study intervention.

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 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over Up to Day 85.

The primary endpoint is the number of participants with adverse events (AEs) and serious adverse events (SAEs) through Day 85. An AE is defined in the registry as an untoward medical occurrence temporally associated with study intervention, whether or not considered related to it. An SAE is an event meeting specified seriousness criteria, including death, a life-threatening event, inpatient hospitalization or its prolongation, persistent or significant disability, a congenital anomaly or birth defect, or another situation judged serious using medical or scientific judgment.

Counting participants with events is a straightforward way to describe how many people in each group experienced at least one event in the specified period. It is useful for summarizing safety observations, while keeping the distinction between any AE and an SAE visible. A participant count does not convey the number of events each participant experienced, the events’ duration or severity beyond the SAE classification, or whether investigators considered an event related to treatment.

The endpoint is descriptive in the posted results: the registry presents group counts, but no analysis results are listed. It therefore supports a report of observed counts, not a formal estimate of a between-group effect. The registry does not report further endpoint details such as a comparative estimand or a statistical testing procedure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The central statistical information in this record is descriptive: group-specific counts of participants with serious adverse events and other adverse events, together with the number at risk for each outcome. There are no posted analysis results. This means the evidence can be described in terms of observed counts, but the registry record does not support a formal test of whether event experience differs between treatment and placebo groups.

What does a participant count represent?

A participant count records how many people had at least one event in the relevant category during the stated follow-up. It is not the total number of event episodes. For example, if one person experienced more than one event, a count of participants would still count that person once for the relevant measure. The registry’s endpoint description distinguishes AEs from SAEs according to its seriousness definition. The posted “other” category is reported separately from serious events; it should not be read as a count of all event episodes.

The denominator, or number at risk, gives the group size used for that outcome. Reading the count with its denominator is more informative than reading the count alone, because the same count can represent different observed proportions in groups of different sizes. No new proportions or pooled totals are calculated in this explanation. The posted results also do not provide uncertainty intervals around event proportions.

Why does a zero count need careful interpretation?

A zero observed count is a statement about what was recorded in the studied group during the follow-up period. It is not evidence that the true probability of an event is exactly zero. General statistical reasoning: when a study has a limited number of participants and a finite observation period, uncommon events may not be observed even if they can occur. The zero serious-event counts should therefore be interpreted alongside the small group sizes and the study’s defined follow-up, rather than as a guarantee about other people or longer periods.

What does randomization contribute?

In general, random assignment can help make comparison groups similar on average with respect to measured and unmeasured characteristics, reducing certain sources of confounding. It does not ensure that small groups will be identical, and it does not remove the need for a clearly specified analysis. The registry identifies the study as randomized and double-blind, but details of the randomization procedure, allocation concealment and any stratification are not reported in the registry record. The group counts should not be interpreted as evidence that randomization achieved balance on particular characteristics.

Double blinding can reduce the influence of knowledge of assigned treatment on some aspects of participant reporting or study assessment. The record does not describe which roles were blinded, how blinding was maintained, or whether it was assessed. Those particulars should not be assumed from the design label alone.

Are the posted counts a treatment-effect estimate?

No comparative effect estimate or inferential analysis is listed. In general, a treatment-effect analysis would state the contrast being estimated, how the groups are compared, and how uncertainty is quantified. For binary outcomes, approaches may compare event proportions or model the probability of an event; the appropriate approach depends on the design, data and analysis objective. No such method, estimate, confidence interval or hypothesis-test result is reported in the registry record. The registry lists zero analyses.

The posted information also does not specify adjustments for cohort membership, dose, participant characteristics or multiple comparisons. In general, adjustment can be useful when it matches a prespecified question and suitable data are available, but it cannot be inferred from descriptive counts. The distinct cohort groupings also make an unqualified pooled contrast difficult to interpret: the placebo groups and active-dose groups do not all represent the same cohort composition.

How should planning illustrations be read?

Any sample-size planning illustration associated with the posted results is not an observed study result and is not a statement of the trial’s original design rationale. The stated illustration assumptions are 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 the observed effect. Such calculations are conditional on those assumptions. They do not establish that the trial had a particular probability of detecting an effect, and they should not be called observed power. The registry record does not report the trial’s sample-size justification.

In general, over-dispersion is relevant when outcome variability exceeds what a statistical model assumes; ignoring it can make uncertainty appear too small. The record does not identify a count model or report evidence of over-dispersion. Since the posted primary results are participant counts without a model-based analysis, no claim about over-dispersion or a model’s adequacy can be made.

10. Multiplicity, Missing Data and Analysis Populations

The registry names multiple study outcomes, including the primary adverse-event endpoint and secondary pharmacodynamic and immunogenicity measures. It does not report a multiplicity strategy, such as a hierarchy of hypotheses, an adjustment to control the chance of false-positive findings across tests, or a distinction between confirmatory and exploratory analyses. The record lists no analysis results, so there are no posted inferential findings for which multiplicity handling can be assessed.

Missing-data methods are not reported in the registry record. The posted counts identify numbers at risk for each group and outcome, but they do not explain whether any participants had incomplete follow-up, how such cases were handled, or whether participants were included only when data were available. The safety population is defined as randomized participants who took at least 1 dose of study intervention. That definition clarifies the intended population for safety summaries, but it does not by itself explain missing observations or withdrawals.

In general, missingness can affect interpretation when the chance of having an observed outcome is related to participant characteristics or event experience. A complete-case summary, an imputation method or another approach would each rely on assumptions and should be described for readers to assess. No such approach is stated. The registry also does not report a separate intention-to-treat analysis population or a per-protocol population. Consequently, the posted safety counts should be read as the available registry summaries, without assuming unreported handling of missing data or a broader analysis population.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures are participant counts, not event totals. The registry reports zero participants with serious adverse events in every listed group, with group-specific numbers at risk of 13, 18, 18, 4, 6 and 6. It also reports zero deaths in every group. These observations cover the safety endpoint timeframe through Day 85.

Zero recorded serious events in these groups is reassuring only as a description of what was observed during this study; it does not establish that serious events are impossible or quantify their frequency precisely. The groups are small, and no confidence intervals or formal comparisons are reported. The counts cannot establish that groups have the same serious-event risk.

Other adverse events are listed separately: the recorded participant counts are 3, 2, 3, 1, 2 and 2 across the groups, with corresponding numbers at risk of 13, 18, 18, 4, 6 and 6. These are descriptive summaries. They do not indicate event severity beyond the separation of serious and other events, causality, duration or recurrence. The registry does not provide event-level terms in the posted serious-event summary.

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

The result describes adverse-event experience recorded among healthy participants who received a single subcutaneous dose of melrilimab or placebo in this Phase 1 study. Across the listed groups, the registry records no serious adverse events and no deaths, while recording other adverse events in each group. This is a summary of observations over the stated follow-up, not a comprehensive estimate of risk.

The findings do not establish whether melrilimab causes or prevents any particular event. The AE definition includes events whether or not they are considered related to study intervention, and the posted count summaries do not provide event-level causality assessments. They also do not report a statistical comparison between dose groups and placebo. The observed counts should not be translated into a claim that treatments are equivalent or that a difference exists.

The study population is healthy participants, not a group described as receiving treatment for asthma. Although the registry lists Asthma among the conditions, the stated purpose and population concern healthy participants. The safety observations therefore do not directly answer questions about outcomes in people with asthma or about repeated dosing. The intervention described is a single dose, and the posted primary endpoint is limited to adverse events and serious adverse events through Day 85.

The registry identifies pharmacokinetic and pharmacodynamic objectives and names secondary outcomes, but the record does not list analyses for those outcomes. The posted safety counts also do not establish longer-term safety, rare-event frequency, or effects in populations beyond the described cohorts. The most defensible reading is narrow: the registry reports the specified group-level event counts during the defined study period, with substantial limits on precision and comparison.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how early-phase safety data need to be read in context. Its randomized, double-blind design and separate dose and cohort groups provide a framework for observing safety after single doses. The endpoint uses participant counts, making the basic summaries readily understandable, while the cohort structure cautions against treating every group as interchangeable.

The registry results also illustrate the difference between a descriptive result and a comparative conclusion. Counts can describe what was recorded, but a comparison requires a defined contrast and an analysis that quantifies uncertainty. The registry record lists no analyses, so the posted counts do not support a formal conclusion about differences between melrilimab and placebo. The absence of serious events in the observed groups is not the same as proof of zero risk.

There is also a useful distinction between an endpoint and the broader objectives of a trial. The study aimed to examine safety, tolerability, pharmacokinetics and pharmacodynamics, but the primary outcome presented is an adverse-event count. Secondary outcomes are named, yet their analyses are not posted in the record. Readers should therefore separate the study’s stated aims from the results available for statistical interpretation.

Finally, any sample-size illustration based on observed effects is conditional planning, not evidence that the study was designed to detect a particular effect or had a given achieved power. This distinction matters because small early-phase studies are often primarily descriptive. Interpreting their findings accurately requires keeping observed counts, statistical uncertainty and generalizability separate.

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 posted safety summaries are based on small, cohort-specific groups, limiting the precision with which event experience can be characterized. The record provides counts and numbers at risk but does not report confidence intervals or comparative estimates. It also does not give event-level descriptions for the other adverse-event counts or further detail on severity, duration, recurrence or investigator-assessed relationship to intervention.

The groups differ in dose and cohort composition. The Japanese and Chinese participant groups receive separate entries, while placebo results are presented in cohort groupings. These features limit the interpretation of broad comparisons across all active and placebo groups. The registry does not report adjusted analyses, a pooled comparison, or the rationale for the grouping structure.

The study concerns single-dose administration in healthy participants, with follow-up through Day 85 for the primary safety endpoint. The posted results do not address repeated dosing, longer-term event experience or outcomes in people being treated for asthma. The registry record does not report detailed participant flow, withdrawals, missing-data handling, or analyses of the named secondary outcomes. These omissions constrain interpretation of both the safety summaries and the study’s wider pharmacokinetic and pharmacodynamic objectives.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety and Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Melrilimab (GSK3772847) in Healthy Participants — NCT04366349.
• Registry record last updated 2021-11-05; status last verified 2021-09.
• Results first posted 2021-11-05.
• 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

NCT04366349 is a completed Phase 1 randomized, double-blind study of single subcutaneous doses of melrilimab in healthy participants. The registry reports enrollment of 65, a start date of 2020-07-21 and a primary completion date of 2020-12-21. Dose groups received 70 mg or 140 mg, with placebo groups and separate Japanese and Chinese participant cohorts.

The primary endpoint counts participants with adverse events and serious adverse events through Day 85. The posted figures report zero serious adverse events and zero deaths in every listed group, alongside other adverse-event counts. No analyses are listed in the registry record. The counts are descriptive and do not establish comparative effects or precise event risks.