A Safety, Tolerability, Pharmacokinetics (PK) and Target Engagement (TE) Study of GSK3858279 in Healthy Participants and Evaluation of the Efficacy of Repeat Doses in Participants With Osteoarthritis (OA): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety, Tolerability, Pharmacokinetics (PK) and Target Engagement (TE) Study of GSK3858279 in Healthy Participants and Evaluation of the Efficacy of Repeat Doses in Participants With Osteoarthritis (OA) (NCT03485365), a randomized phase 1 study. The primary outcome is Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).

2. Clinical Question

The study’s questions differ by part. Part A was designed to describe safety and tolerability after a single dose while assessing pharmacokinetics, target engagement and immunogenicity. Its ascending-dose cohorts included intravenous administration in Cohorts 1 through 5 and subcutaneous administration in Cohort 6. These cohorts are not interchangeable treatment groups: route and dose escalation are part of the design, so a simple pooled contrast would not describe a single common exposure.

Part B focused on repeat subcutaneous dosing in participants with osteoarthritis of the knee. Its intended efficacy evaluation concerned pain, with placebo as the comparator. The registry record identifies these aims but does not report a pain outcome result in the registry record for this analysis. It therefore supports a description of the trial’s questions and posted safety counts, but not a conclusion about the comparative pain results.

3. Trial Design

This was a randomized, double-blind, placebo-controlled Phase I study with a sequential model. The registry lists enrollment of 97 and status as completed. The study had two parts with different populations and objectives: healthy participants were studied in Part A, while Part B evaluated repeat dosing in participants with osteoarthritis of the knee.

Part A used a single ascending-dose design. The brief summary describes approximately 48 healthy participants in 6 cohorts, randomized in a 3:1 ratio to GSK3858279 or placebo. Cohorts 1 through 5 received intravenous GSK3858279; Cohort 6 received it subcutaneously. Placebo was matched to the intravenous or subcutaneous route. The registry names safety, tolerability, pharmacokinetics, target engagement and immunogenicity as Part A evaluation domains. Sequential dose escalation is relevant to interpretation: cohorts reflect steps in an escalating study design, rather than a set of concurrent groups all receiving the same route and dose.

Part B was a parallel-group, repeat-dose evaluation. The brief summary describes approximately 50 participants with osteoarthritis randomized in a 1:1 ratio to subcutaneous GSK3858279 or matching placebo. Its stated aims included safety, tolerability, efficacy for pain, pharmacokinetics, target engagement and immunogenicity. The registry record does not report the dose levels or the interval between repeat doses.

The study was double-blind and randomized, but the registry record does not report further details about the blinding procedures, allocation concealment, or how the sequence was generated. It also does not report a sample-size justification or a full statistical analysis plan. These absences matter because design labels alone do not establish how allocation was implemented or how outcome comparisons were planned. The posted record identifies the broad design and intended questions, while leaving those operational and analytical details unspecified.

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 97 participants were enrolled in the study. Out of which 49 participants enrolled in Part A and 48 participants in Part B of the study.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population comprised of all randomized participants who received at least one 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 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), measured over Up to 141 days.

The primary endpoint is the number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) in Part A, over a timeframe of up to 141 days. The registry defines an adverse event as an untoward medical occurrence temporally associated with study intervention, whether or not it is considered related to that intervention. A TEAE is an adverse event occurring on or after the first dose. The registry’s SAE definition includes events such as death, life-threatening events, inpatient hospitalization or its prolongation, persistent or significant disability or incapacity, congenital anomaly or birth defect, and other events judged serious by the investigator.

Counting participants with these events is a safety-oriented endpoint. It describes how many participants experienced an event, rather than the total number of event episodes or the severity of every event. Separating TEAEs from SAEs is useful because the categories capture different aspects of safety: treatment-emergent timing identifies events arising after dosing begins, while seriousness reflects specified consequences or investigator judgment. These counts can help characterize safety observations during the study, but counts alone do not establish causality. The endpoint’s stated population is the safety population: randomized participants who received at least one dose of study intervention.

The primary endpoint belongs to Part A. It should not be conflated with Part B’s planned evaluation of pain or with the pharmacokinetic outcomes listed as secondary outcomes. The registry record does not report a single comparative estimate for the primary endpoint in the material.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The available numerical results are counts of participants with events, so the natural starting point is descriptive. A count answers how many participants in a group were recorded with the event category. The number at risk gives the group size associated with that count. Neither quantity by itself explains why an event occurred, whether it was related to treatment, or whether the difference between groups is more than might occur by chance.

What do event counts tell us?

For a binary outcome such as whether a participant experienced an event, each participant is classified according to event status for the specified outcome and observation period. The registry’s primary endpoint counts participants with TEAEs and SAEs. The posted adverse-event listings also distinguish serious events from other events. Counts are straightforward to read, but they retain less detail than a complete event history: they do not show how many separate episodes each participant had, when each event began, how long it lasted, or whether it recurred. Those details are not reported in the registry record.

A comparison between groups can be expressed in several ways, such as a difference in event proportions or a relative measure. These measures answer different questions and depend on the outcome definition and analysis population. No comparative effect estimate or confidence interval for these safety counts is reported in the registry record. It would therefore be inappropriate to infer a precise treatment contrast from the raw counts alone. General statistical principle: a confidence interval communicates the range of values compatible with an estimate under the model and assumptions used. It conveys uncertainty, not the probability that a particular treatment effect is true.

Why does the design affect the comparison?

Randomization is intended to make treatment groups comparable on average, while blinding can reduce the influence of treatment knowledge on participant reporting and outcome assessment. The registry identifies the study as randomized and double-blind. It does not report the sequence-generation or allocation-concealment procedures, so those implementation details cannot be assessed from this record. Part A’s sequential dose escalation and its different administration routes also matter: the cohorts represent distinct stages and routes, not a single parallel comparison of identical exposure conditions. Part B, by contrast, is described as a parallel-group comparison of repeat subcutaneous GSK3858279 and matching placebo.

General statistical principle: an estimate from a randomized comparison is most interpretable when the groups, outcome definition, follow-up and analysis population align with the question being asked. Combining groups with different routes or dose stages can obscure rather than clarify the contrast. The Part A placebo group is pooled, while the active-treatment results are listed by cohort. The registry record does not report an analysis plan explaining whether or how those data were intended to be combined for formal comparisons.

How should planning calculations be read?

The planning illustration assumptions described for this record use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They define the effect to detect as a stated fraction of an observed effect. Such calculations are planning illustrations, not evidence about the probability that a completed study detected an effect. They should not be called observed power. A planned sample size depends on the outcome, the assumed effect, variability or event frequency, the design and the desired operating characteristics. The registry record does not report the trial’s own sample-size justification, so the illustration assumptions should not be mistaken for the original design rationale.

For binary outcomes, event frequency is especially important to planning and precision. Sparse events can produce imprecise estimates; a zero count in a group does not establish zero underlying risk. General statistical principle: when data are sparse, conventional approximations may perform poorly, and the method used to construct an interval or test can affect the result. The registry record does not report a model or method for inferential analysis of the safety counts, so no specific analytical approach should be attributed to the investigators.

The study also includes pharmacokinetic outcomes expressed through serum concentrations and areas under the concentration-time curve. These are distinct from the binary safety endpoint. General statistical principle: concentration-time data describe exposure over time, while an area-under-the-curve measure summarizes exposure across a specified interval. The listed secondary outcomes name these measures, but numerical results and their analysis methods are not reported in the registry record. Likewise, target engagement and immunogenicity are stated study aims, but their results are not available in the record details used for this interpretation.

Multiplicity arises when many outcomes, time points or comparisons are tested. General statistical principle: as the number of tests increases, the chance of obtaining at least one apparently notable result by chance may also increase if no adjustment or hierarchy is used. The registry lists 43 outcome measures and 2 analyses, but it does not report the planned multiplicity strategy or how outcomes were prioritized statistically. The primary endpoint itself includes TEAEs and SAEs, and the posted data do not furnish a single effect estimate that resolves these categories into one comparison. No specific statistical test, adjustment, or model can be inferred from the endpoint list alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 43 outcome measures and 2 analyses. A study with multiple outcomes may involve many opportunities for comparisons across outcome types, time points, treatment groups or parts. General statistical principle: multiplicity can increase the chance of a nominally notable result when many tests are considered, so plans may use a hierarchy, adjustment or clearly defined primary analysis. The registry record does not report a multiplicity strategy, an outcome hierarchy beyond identifying the Part A primary endpoint, or the role assigned to each analysis.

Missing-data handling is also not reported in the registry record. The available description does not state how missing observations, withdrawals, incomplete follow-up or unavailable measurements were handled for the safety endpoint or the planned Part B efficacy and pharmacokinetic outcomes. General statistical principle: missingness can affect interpretation when the likelihood of missing data is related to participant characteristics, treatment, outcome status or tolerability. Without a reported approach and relevant information about missing observations, the impact cannot be assessed.

The primary endpoint specifies a safety population comprising randomized participants who received at least one dose of study intervention. The registry record does not report the analysis populations used for the other outcomes or whether any efficacy analysis used an intention-to-treat or other defined population. It also does not report a detailed statistical analysis plan, model specifications, covariate adjustments, or methods for handling repeated measurements. These omissions limit assessment of whether the posted results follow prespecified methods. They do not establish that such methods were absent in the conduct of the study; they are simply not reported in 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 1% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event counts are 0 for each listed Part A GSK3858279 cohort, 0 for Part A pooled placebo, 0 for Part B GSK3858279 and 0 for Part B placebo. The reported number at risk is 6 for each Part A GSK3858279 cohort, 13 for Part A pooled placebo, and 24 for each Part B group. The registry also reports 0 deaths in every listed group. These are descriptive participant counts during the reported safety observation, not evidence that the risk of a serious event is absent.

Other adverse-event counts are listed separately: 2, 2, 4, 6, 6 and 6 for Part A GSK3858279 Cohorts 1 through 6; 12 for Part A pooled placebo; 21 for Part B GSK3858279; and 15 for Part B placebo. They should be read with the corresponding group sizes and with the distinction between Part A’s sequential cohorts and Part B’s parallel groups in mind. The registry record does not report comparative estimates, confidence intervals, or tests for these counts, and the registry entries do not detail event severity, duration, recurrence or relatedness for the other-event category. Counts alone do not establish that an event was caused by study intervention.

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

The available results describe selected safety observations from a completed Phase I study. They show that the registry recorded no serious adverse events and no deaths in the listed groups, while also recording participants with other adverse events. The counts differ across groups, but they do not by themselves quantify a reliable treatment effect. Group size, route of administration, dose-escalation stage, population and follow-up all shape how a count should be interpreted. In particular, Part A cohorts are sequential and include intravenous and subcutaneous administration, whereas Part B is a parallel repeat-subcutaneous-dose comparison.

These findings do not establish that GSK3858279 is safe or unsafe in a broader population. A finite study with the reported group sizes cannot rule out uncommon events, and zero observed serious events does not mean that the underlying possibility is zero. The registry entries do not include inferential estimates that would express the precision of a between-group safety comparison. Nor do the listed counts establish that any event was caused by the intervention.

The registry’s stated Part B aim included evaluating efficacy for pain in participants with osteoarthritis of the knee. That aim is not itself an efficacy result. No pain comparison, effect estimate, confidence interval or statistical test is reported in the record details available for this analysis. The same applies to numerical findings for pharmacokinetics, target engagement and immunogenicity: they are named study domains or outcomes, but their results are not reported in the registry record.

The study’s design provides a framework for evaluating initial exposure and repeat dosing, but interpretation depends on information not present in the registry record, including detailed analysis methods, missing-data handling and a sample-size justification. The most defensible reading is therefore narrow: the posted data give descriptive adverse-event counts for the listed groups, while the broader comparative safety and efficacy questions remain unresolved by these registry entries. No treatment recommendation follows from these registry counts.

13. Why This Trial Matters Statistically

The study is statistically notable for combining two distinct questions in one randomized Phase I program. Part A examined single ascending doses in healthy participants, including intravenous and subcutaneous routes, while Part B evaluated repeat subcutaneous dosing in participants with osteoarthritis of the knee. Keeping these parts distinct is essential: their populations, dosing patterns and objectives differ, so their results should not be collapsed into a single treatment comparison without a prespecified rationale.

It also illustrates how safety counts can be informative yet limited. Counts communicate observed events directly and can flag the need to understand event type, timing and clinical context. But they do not automatically provide an estimate of comparative risk or its precision. The serious-event counts are zero across the listed groups, while other adverse-event counts are reported. Neither pattern alone establishes causality or excludes a risk that was not observed during the study.

For researchers, the registry record highlights the importance of transparent analysis details. It identifies a primary safety endpoint and a safety population, but does not report the statistical plan, sample-size justification, multiplicity strategy or missing-data methods in the registry record for this interpretation. Those details matter when moving from descriptive counts to formal comparisons. A design description and an outcome list are not substitutes for a specified model and analysis population.

The record also makes clear that intended outcomes and reported results are different. Part B was planned to assess pain efficacy, alongside pharmacokinetic, target-engagement and immunogenicity outcomes. Those aims cannot be treated as findings in the absence of results. The statistical lesson is to separate what the design set out to evaluate from what the posted data actually quantify, and to match the strength of interpretation to the precision and completeness of the reported evidence.

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 information is limited to participant counts by listed group. It does not include comparative effect estimates, confidence intervals or inferential tests for the adverse-event outcomes. The record details also do not describe individual event types beyond the serious-event category, severity grading, timing, duration, recurrence or attribution to treatment. Consequently, the counts offer a restricted view of the safety experience.

Part A’s design requires particular caution. It used sequential dose escalation, with intravenous administration in Cohorts 1 through 5 and subcutaneous administration in Cohort 6. The groups therefore differ by stage and route, and the Part A placebo group is pooled. The registry record does not report details of the dose levels or the analytical rationale for pooling placebo observations. Direct comparisons between an individual cohort and pooled placebo may not represent a common, concurrent contrast.

Part B has a parallel-group design and reports 24 participants at risk in each group, but the registry record does not report a comparative analysis of the safety counts or the planned pain efficacy results. It also does not report the extent of missing observations or follow-up by group. Without those details, the completeness and precision of comparisons cannot be evaluated.

Finally, the registry record does not report the trial’s own sample-size justification, detailed statistical analysis plan, multiplicity strategy, or methods for missing data. It does not report the implementation details of randomization and blinding. These limitations concern what is documented in the record; they do not demonstrate that the study team did not address these matters elsewhere. They do, however, constrain what can be concluded from the registry information alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Safety, Tolerability, Pharmacokinetics (PK) and Target Engagement (TE) Study of GSK3858279 in Healthy Participants and Evaluation of the Efficacy of Repeat Doses in Participants With Osteoarthritis (OA) — NCT03485365.
• Registry record last updated 2024-03-22; status last verified 2023-09.
• Results first posted 2024-03-22.
• 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

NCT03485365 is a completed, randomized, double-blind, placebo-controlled Phase I study sponsored by GlaxoSmithKline, with enrollment of 97. Its sequential, two-part design studied single ascending doses in healthy participants and repeat subcutaneous doses in participants with osteoarthritis of the knee. Part A included intravenous and subcutaneous cohorts; Part B compared subcutaneous GSK3858279 with matching placebo.

The primary endpoint was the number of Part A participants with TEAEs and SAEs, with follow-up up to 141 days. The posted safety counts report 0 serious adverse events and 0 deaths in every listed group, alongside group-specific counts for other adverse events. The record details do not report a comparative estimate or inferential analysis for these counts. Although Part B was intended to evaluate pain efficacy, its efficacy results, along with numerical pharmacokinetic, target-engagement and immunogenicity results, are not reported in the registry record.