A Study to Investigate the Safety and Pharmacokinetics of a Single Dose of VH3810109 (Also Known as GSK3810109), Administered Either Subcutaneously (SC) With rHuPH20 or Intravenously (IV), in Healthy Adult Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Investigate the Safety and Pharmacokinetics of a Single Dose of VH3810109 (Also Known as GSK3810109), Administered Either Subcutaneously (SC) With rHuPH20 or Intravenously (IV), in Healthy Adult Participants (NCT05291520), a non-randomized phase 1 study. The primary outcome is Number of Participants With Grade 2 or Higher (>=) Adverse Events (AEs) Following SC Administration of VH3810109 (Part 1 and Part 3).

2. Clinical Question

The study also assessed safety, tolerability and pharmacokinetics after a single dose. Its listed secondary outcomes include measures of plasma concentration over time, maximum observed concentration, time to maximum concentration and apparent terminal half-life. For the subcutaneous groups, the registry also lists injection-perception outcomes, including acceptance, pain, and whether pain or local reactions bothered or affected participants.

The study is described as a two-part study in its brief summary, while the registry lists three groups across Parts 1, 2 and 3. The posted arm descriptions distinguish two subcutaneous groups and one intravenous group. These groups differ in dose and/or route, and their allocation was non-randomized. The clinical question is therefore descriptive: it concerns the recorded outcomes in each study group, rather than a randomized estimate of the effect of one route or dose compared with another.

Although the registry identifies the primary safety outcome and its follow-up period, the participant counts for that outcome are not reported in the registry record. The posted adverse-event figures include serious-event counts and another adverse-event count, but those figures do not establish the result for the specified primary endpoint.

3. Trial Design

This was a Phase 1, open-label, single-dose study of VH3810109 in healthy adults. It is listed as completed. The registry gives a start date of 2022-02-23 and a primary completion date of 2023-04-10. Its stated enrollment is 24.

The study used a sequential, non-randomized design with no masking. Part 1 received VH3810109 20 mg/kg with rHuPH20 by subcutaneous injection at Day 1. Part 2 received VH3810109 60 mg/kg intravenously at Day 1. Part 3 received VH3810109 3000 mg with rHuPH20 by subcutaneous injection at Day 1. Each group description states that participants were followed for up to 24 weeks. The registry lists 8 participants at risk in each group for the posted adverse-event figures.

The primary outcome was the number of participants with Grade 2 or higher adverse events following subcutaneous administration in Part 1 and Part 3, through Week 24. The stated primary analysis population was the Safety set: participants who received at least one dose and had data for the assessed timepoints and analysis. The registry does not report the outcome counts for this primary measure.

Because assignment was not randomized and the study proceeded sequentially, the groups should not be treated as exchangeable treatment arms. The intravenous group differs from the subcutaneous groups in route and dose; the two subcutaneous groups also differ in dose. The registry record does not report a randomized allocation process, masking, or a concurrent control group designed for a like-for-like comparison.

Pharmacokinetic outcomes included area under the plasma concentration-time curve, maximum observed concentration, time to maximum concentration and apparent terminal half-life. Injection-related outcomes were listed for Parts 1 and 3. The specific analysis methods, timing of individual assessments, and sample-size justification 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: Analysis was performed on the Safety set which included all participants that received at least one dose of the study intervention and had data for the assessed timepoints and analysis.

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 With Grade 2 or Higher (>=) Adverse Events (AEs) Following SC Administration of VH3810109 (Part 1 and Part 3), measured over Up to Week 24.

The primary endpoint is the number of participants with at least one Grade 2 or higher adverse event following subcutaneous VH3810109 in Part 1 and Part 3, with assessment through Week 24. The registry describes an adverse event as an untoward medical occurrence temporally associated with study intervention, whether or not it is considered related to that intervention. The severity grading used the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. In that grading system, Grade 1 is mild, Grade 2 moderate, Grade 3 severe and Grade 4 potentially life threatening.

Counting participants who reach a specified severity threshold is a way to describe how many experienced events meeting that threshold during the stated follow-up. It differs from counting every event: a participant may have more than one event, but the endpoint is expressed as participants. In general, a severity threshold can focus attention on events above a defined level while retaining a clear clinical interpretation.

The registry record identifies the endpoint and population but does not report its participant counts. The posted serious-event and other-adverse-event figures are not a substitute for the Grade 2-or-higher endpoint: they do not report the same outcome definition and do not supply the primary endpoint result. The reason this threshold was selected, beyond its use as the stated primary measure, is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary outcome is a count of participants who experienced at least one adverse event meeting the Grade 2-or-higher threshold during the stated follow-up. This is a participant-level measure, not a tally of all events. In general, counting participants answers how many people had an event, whereas counting events answers how many occurrences were recorded. Those summaries can differ when one participant experiences more than one event.

The outcome definition also sets a severity threshold. The registry describes Grade 2 as moderate and includes higher grades in the endpoint. General interpretation of a thresholded outcome depends on consistent event collection and grading. The record states which grading framework was used, but the endpoint results themselves are not reported in the registry record.

Why does the design affect interpretation?

Random allocation is a general method for making treatment groups comparable on average, including on factors that may not be measured. This study is listed as non-randomized and sequential. The groups also differ in route and dose: Part 1 and Part 3 received subcutaneous treatment at different doses, while Part 2 received intravenous treatment at a different dose. A direct comparison of their outcomes would therefore mix the effects of route, dose, and any other group differences. The registry explicitly cautions that the arms are not a like-for-like control comparison.

Open-label means the study was not masked, according to the registry. In general, lack of masking can affect reporting or assessment of subjective outcomes, such as perceptions of injection pain. The record lists such outcomes for the subcutaneous groups, but does not report the detailed procedures used to collect or assess them.

What can the adverse-event fields tell us?

The posted figures are counts with associated numbers at risk, which are straightforward descriptive summaries. The serious-event field lists no participants with serious events in any of the three groups; the other-adverse-event field lists 8 in Part 1, 1 in Part 2 and 8 in Part 3. The death counts are zero for each group. These are the recorded summaries and do not by themselves identify the severity, timing, relatedness, or clinical importance of the events in the other-adverse-event field.

General statistical uncertainty matters when interpreting event counts. A confidence interval, when reported, describes a range of values compatible with the data under the interval's statistical assumptions; it does not guarantee that the true value lies in that range. Confidence intervals for the primary endpoint are not reported in the registry record. The absence of a reported interval makes it harder to assess precision beyond the observed counts, and the primary counts themselves are also not reported.

How should pharmacokinetic outcomes be understood?

The listed pharmacokinetic outcomes include area under the plasma concentration-time curve, which generally summarizes exposure over a specified time span; maximum observed concentration, which describes the highest measured concentration; time to maximum concentration, which records when that maximum occurred; and apparent terminal half-life, which characterizes the terminal decline in concentration. These measures describe different aspects of concentration over time. The registry names outcomes but does not report their numerical results in the record, so no numerical pharmacokinetic comparison can be made.

In general, estimates of pharmacokinetic measures depend on the sampling schedule and analysis approach. The registry does not report the detailed sampling schedule or statistical methods used for these measures. They should not be inferred from the treatment assignments or from the safety counts.

What do planning illustrations mean?

General sample-size planning considers the effect a future study aims to detect, variability, the chosen significance level, allocation, and a statistical model. The registry's stated planning illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. The registry notes that illustrations for time-to-event outcomes count total events, while other illustrations count participants per arm.

Such calculations are planning illustrations, not results from this completed study. In particular, power calculated from an observed effect is not observed power and does not establish that a result is reliable. The registry does not report its own protocol-based sample-size justification. The design of this study is non-randomized and its arms are not a like-for-like comparison, so a planning calculation based on a two-arm comparison should not be mistaken for evidence from a randomized comparison.

The registry reports zero analyses in its analysis count. The specific inferential model, any adjustment procedure, and the analysis plan are not reported in the registry record. No recalculated comparison or statistical test should be treated as the sponsor's primary analysis; the sponsor's own analysis takes precedence if a discrepancy is identified.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Part 1 Group: VH3810109 20 mg/kg + rHuPH20 [SC]", "Part 3 Group: VH3810109 3000 mg + rHuPH20 [SC]")
n      <- c(8, 8)
events <- c(7, 8)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Part 1 Group: VH3810109 20 mg/kg + rHuPH20 [SC]  8  7  87.5  47.3  99.7  52.9  97.8  51.8  97.2
ARM  Part 3 Group: VH3810109 3000 mg + rHuPH20 [SC]  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 34 outcome measures, including the primary safety endpoint, pharmacokinetic measures, and injection-perception outcomes. When a study assesses multiple outcomes, general statistical practice may need to consider multiplicity: the chance of obtaining an apparently notable result can increase as more hypotheses are tested. Whether and how that issue was addressed depends on a prespecified analysis plan. Multiplicity procedures and a statistical analysis plan are not reported in the registry record.

The registry reports 0 analyses in its analysis count. This does not provide a statistical testing strategy, nor does it establish that no analyses were conducted outside the registry record. The method used for each outcome, any planned comparisons, and whether analyses were adjusted for multiple testing are not reported in the registry record.

The stated primary analysis population is the Safety set. It included participants who received at least one dose and had data for the assessed timepoints and analysis. The record does not report how missing outcome data were handled, how many participants had missing data, or whether any sensitivity analyses were planned or conducted. The reasons for missingness and the extent to which missing data could affect the endpoint are therefore not reported in the registry record.

These omissions limit interpretation of both the primary endpoint and secondary outcomes. The record identifies the endpoint definition and population, but without the primary counts, missing-data details, or analysis plan, readers cannot assess the precision or robustness of the endpoint result from the registry record.

12. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 0 participants with serious adverse events among 8 at risk in Part 1, 0 among 8 in Part 2, and 0 among 8 in Part 3. It also lists 0 deaths in each group. The most common serious adverse-event terms are not listed.

The separate other-adverse-event field lists 8 participants in Part 1, 1 in Part 2, and 8 in Part 3, each among 8 at risk. These counts should be read as the registry's entries for that field, not as the primary outcome. The primary endpoint is specifically Grade 2 or higher adverse events after subcutaneous dosing in Parts 1 and 3 through Week 24; its counts are not reported in the registry record.

A zero serious-event count means none were recorded in that field for the stated group. It does not show that the risk is absent, and a count alone does not describe the precision of an underlying event rate. In general, confidence intervals or other uncertainty summaries help show how much uncertainty remains around an observed count. Such uncertainty measures are not reported for these safety figures. Nor do the counts provide event details, timing, relatedness, or duration.

Because the study groups were non-randomized, sequential, and differed in dose and route, the counts should not be used as a direct comparative safety estimate between routes or doses.

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

The posted record describes a completed Phase 1 study that evaluated a single dose of VH3810109 by subcutaneous or intravenous administration in healthy adults. It identifies the primary safety question, the grading framework, the groups, and follow-up through 24 weeks. The available adverse-event figures record no serious adverse events and no deaths in any listed group, alongside counts in the other-adverse-event field.

These findings do not answer the primary endpoint as defined, because the participant counts for Grade 2 or higher adverse events in the subcutaneous groups are not reported in the registry record. The other-adverse-event counts cannot be substituted for that endpoint. The listed pharmacokinetic and injection-perception outcomes also do not convey their results without numerical outcome data.

In general, absence of a recorded event in a small study group is not proof that the event cannot occur. A study's ability to characterize uncommon events depends on the amount and duration of observation, as well as event ascertainment. The registry does not provide the uncertainty estimates needed to quantify precision for the stated primary outcome.

The results should not be read as a randomized comparison. Allocation was non-randomized, the study was sequential and open-label, and the groups differed by route and dose. Consequently, the observed group counts cannot isolate the effect of route, dose, or rHuPH20. The record also does not report a concurrent control group intended to support a like-for-like comparison.

Overall, the registry record supports a description of the study design and the posted safety counts, but it does not provide enough reported outcome detail to quantify the primary endpoint or compare pharmacokinetic outcomes. It does not establish a treatment effect or provide a complete assessment of safety.

14. Why This Trial Matters Statistically

This trial illustrates why outcome definitions and posted results need to be read together. The primary outcome is a participant count meeting a defined severity threshold, while the adverse-event figures available in the registry are presented in serious-event and other-adverse-event fields. Similar-sounding safety summaries are not interchangeable: an event category, a severity threshold, and a participant-level endpoint answer different questions.

It also illustrates the limits of comparisons across non-randomized groups. The study includes subcutaneous and intravenous administration, but route is not the only feature that differs: dose differs as well, and the arms were assigned sequentially rather than randomly. Descriptive differences therefore cannot isolate a route effect or support a like-for-like comparison.

The record lists multiple pharmacokinetic and injection-perception outcomes in addition to the primary safety endpoint. When many outcomes are considered, a prespecified analysis strategy helps readers distinguish confirmatory questions from exploratory descriptions. The registry record does not report such a strategy or a multiplicity approach.

Finally, the record demonstrates the importance of reporting outcome values alongside design details. It specifies the primary endpoint and follow-up period, but the primary participant counts and their uncertainty are not reported. Without them, readers cannot evaluate the endpoint's observed frequency or precision. Transparent outcome reporting is essential for statistical interpretation, particularly when a study is small and its groups are not designed for direct causal comparison.

15. 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.

Important limitations follow from the registry record. The study was non-randomized, sequential and open-label. Its three groups differed in route and dose, so the groups do not provide a like-for-like comparison. The registry itself flags that the arms are not a randomized comparison.

The primary endpoint is defined, but its participant counts are not reported in the registry record. The record also does not report confidence intervals or other uncertainty measures for the primary outcome. As a result, the primary safety outcome cannot be quantified from the posted results.

The serious-event and death counts are descriptive and do not establish that the underlying risks are absent. The record does not list the most common serious-event terms. For the other-adverse-event field, the counts are present, but detailed event characteristics and their relationship to the primary severity-threshold endpoint are not reported.

The registry lists pharmacokinetic and injection-perception outcomes but does not report numerical results for them in the record. The statistical analysis plan, multiplicity approach, missing-data handling, and reasons for missing data are not reported in the registry record. The study's sample-size justification is also not reported. The registry gives a follow-up duration of up to 24 weeks, so these results do not describe observation beyond that period.

The study population is described as healthy adults. The registry record does not establish how findings would apply to other populations or settings. These limitations constrain the conclusions that can be drawn from the posted information, independently of the treatment groups' observed counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Investigate the Safety and Pharmacokinetics of a Single Dose of VH3810109 (Also Known as GSK3810109), Administered Either Subcutaneously (SC) With rHuPH20 or Intravenously (IV), in Healthy Adult Participants — NCT05291520.
• Registry record last updated 2024-09-19; status last verified 2024-04.
• Results first posted 2024-09-19.
• 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.

19. Record Summary

NCT05291520 is a completed Phase 1, open-label, non-randomized, sequential study of a single dose of VH3810109 in healthy adults. The listed groups received 20 mg/kg subcutaneously with rHuPH20, 60 mg/kg intravenously, or 3000 mg subcutaneously with rHuPH20. Each group was followed for up to 24 weeks.

The primary endpoint was the number of participants with Grade 2 or higher adverse events after subcutaneous administration in Parts 1 and 3. Its participant counts are not reported in the registry record. The posted adverse-event figures list 0 participants with serious adverse events and 0 deaths in each group; the other-adverse-event field lists 8, 1 and 8 participants, respectively, among 8 at risk in each group.

The registry lists pharmacokinetic and injection-perception outcomes, but their numerical results, the statistical analysis plan, missing-data methods, multiplicity procedures, and sample-size justification are not reported in the registry record.