Study to Evaluate Safety and Tolerability of a Single Dose of PF-06741086 in Chinese Adult Participants With Severe Hemophilia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate Safety and Tolerability of a Single Dose of PF-06741086 in Chinese Adult Participants With Severe Hemophilia (NCT04878731), a na phase 1 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs).

2. Clinical Question

The clinical question was principally about safety and tolerability after a single dose in the specified population. The study also set out to characterize pharmacokinetics and pharmacodynamics. Its listed secondary outcomes include marstacimab concentration over time and pharmacokinetic measures such as maximum concentration, time to maximum concentration, area under the concentration-time profile, terminal half-life, apparent volume of distribution, and apparent clearance.

These questions are descriptive in a single-arm study: the observations can characterize what was recorded among participants who received the intervention, but they cannot establish how those observations compare with a concurrent untreated or alternative-treatment group. The registry lists 6 participants at risk in its safety results and reports 0 serious adverse events, 1 participant in the other adverse-event category, and 0 deaths. Those safety counts do not substitute for the missing result for the primary endpoint, which is specifically the number of participants with treatment-emergent adverse events.

3. Trial Design

This was a Phase 1, single-arm, open-label, non-randomized, non-controlled, multicenter study. The registry record lists enrollment of 6 and describes the study intervention as one 300 mg subcutaneous dose of PF-06741086. Participants and study personnel were not masked, and there was no allocation between treatment groups because the study had a single group.

The study record describes Chinese adult participants with severe hemophilia. Its analysis population for the primary outcome included enrolled participants who received at least one dose of study intervention. The safety results list 6 participants at risk. The record does not report additional details about participant selection, eligibility criteria beyond the stated population, study sites, or the number of sites.

The primary outcome concerned treatment-emergent adverse events from Day 1 to Day 42. The stated secondary outcomes concern marstacimab pharmacokinetics, including concentration at specified study days and several summary measures of concentration over time. The brief summary also describes pharmacodynamics among the study aims. The registry lists 54 outcome measures but no analyses in its analysis listing.

The record gives a study start date of 2021-04-16, a primary completion date of 2021-08-10, and a completed status. These dates and status describe the registry entry; they do not fill in the missing primary-endpoint result. No concurrent comparator was included, so estimates from the study are not controlled contrasts. The record does not report a statistical analysis plan or explain a planned sample-size justification.

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 6 participants were enrolled and received a single dose of marstacimab 300 mg.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The analysis population included all enrolled participants who received 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.

Population: Baseline analysis population included all participants enrolled in the study who received the study intervention.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs), measured over Day 1 to Day 42.

The primary endpoint is the number of participants with treatment-emergent adverse events (TEAEs) during Day 1 to Day 42. The record defines an adverse event as an untoward medical occurrence in a participant who received study drug, regardless of whether it was considered caused by treatment. A TEAE is an event that started during the effective duration of treatment, whether or not a similar event existed at baseline. Treatment-related TEAEs were determined by the investigator.

This endpoint is a participant count: it asks how many participants experienced at least one event meeting the endpoint definition, rather than how many events occurred in total. Such a count is useful for describing the proportion of an observed study group with an event, although this record does not report the primary outcome result or a percentage. It is also important to distinguish the endpoint from the registry’s serious and other adverse-event counts. Those safety categories do not, by themselves, establish which events met the primary TEAE definition or the event-onset criteria.

The record says adverse-event grades were defined using National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0, with descriptions for Grades 1 through 5. However, no grade-specific primary-endpoint results are reported in the registry record. Without the result, readers cannot assess the observed count for the primary endpoint from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a binary primary outcome expressed as a participant count. It does not describe a statistical analysis for that endpoint. The distinction between an endpoint definition and an analysis method matters: the definition says what is intended to be counted, while an analysis plan would explain how the count is summarized, what denominator is used, how missing observations are handled, and whether uncertainty is quantified. Those analysis details are not reported in the registry record.

What does a participant count represent?

For an outcome defined as participants with an event, each participant is classified according to whether the event definition was met during the specified observation period. The resulting count is a descriptive summary. It is not the same as a total event count, because one participant can have more than one event. The registry’s primary outcome title asks for the number of participants with TEAEs; the record does not state the numerical result for that endpoint.

General statistical explanation: an event proportion is often accompanied by an uncertainty interval when the aim is to convey how imprecisely the observed count estimates an underlying event frequency. A confidence interval describes a range of values compatible with the data under a specified method and assumptions; it does not guarantee that the underlying value lies in that range. The registry record does not report a confidence interval for the primary endpoint or for the adverse-event counts. With sparse counts, interval estimates can be especially wide, so a count alone should not be read as a precise estimate of risk.

Why does the single-arm design matter?

There is no randomized comparison in this study. Random allocation, when used, can help make treatment groups comparable on average, while a concurrent control group provides a basis for estimating a between-group contrast. Neither feature is present in this single-group design. The observed safety counts therefore describe this study group; they cannot isolate an intervention effect from background events, participant characteristics, observation procedures, or other influences.

Open-label status means the study was not masked. The registry lists masking as none. General statistical explanation: knowledge of treatment assignment can affect how events are noticed, reported, assessed, or attributed, especially for outcomes involving clinical judgment. The record notes that investigators determined whether TEAEs were treatment-related, but it does not report blinding of outcome assessment or procedures for adjudicating events. Treatment-related assessments should also be distinguished from the primary event definition, which includes adverse events regardless of causal relationship.

What can pharmacokinetic summaries tell readers?

The listed secondary outcomes include plasma concentration over time, maximum concentration, time to maximum concentration, area under the concentration-time profile, terminal half-life, apparent volume of distribution, and apparent clearance. These are measures used in general to describe how measured drug concentration changes over time and to summarize aspects of exposure and disposition. They are not themselves direct measures of clinical benefit. The registry record does not report numerical results for these outcomes, so their values, variability, and precision cannot be interpreted from this record.

General statistical explanation: concentration measurements collected at multiple times may be summarized by time point or through derived measures. The interpretation of a summary depends on the sampling schedule, the measurement method, handling of values below quantification limits, and the analysis population. The record lists several collection days within its concentration outcome description, but does not report detailed analysis methods, missing-measurement rules, or the numerical results. These details should not be inferred from the outcome labels.

How should planning calculations be read?

General statistical explanation: sample-size planning uses assumptions about the effect to be detected, variability or event frequency, significance level, power, allocation, and statistical method. Changing those assumptions changes the resulting planning estimate. A planning illustration based on a fraction of an observed effect is hypothetical: it asks what sample size might be needed under its stated assumptions, rather than describing the study’s enrollment rationale. Any sample-size illustrations associated with the record are not observed power and are not evidence that the trial was designed with those targets.

The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. The study itself was single-arm, so these hypothetical two-arm assumptions are not a description of its actual design. The record does not report the protocol’s sample-size justification. Numerical planning estimates should not be treated as results of this trial or as proof that the study had adequate power.

The registry lists no analyses in its analysis listing. This does not establish that no statistical work was done; it means the registry record does not provide analyses in that listing. In the absence of a reported analysis plan or endpoint result, readers should separate the study’s stated objectives and outcome definitions from statistical conclusions that cannot be supported by the record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 54 outcome measures, including the primary safety outcome and secondary pharmacokinetic measures. It does not report a multiplicity strategy. Multiplicity concerns arise when many outcomes or comparisons are tested: under general statistical principles, repeated testing can increase the chance of at least one apparently noteworthy result unless the analysis plan accounts for the number and relationship of tests. No multiplicity adjustment or hierarchy of testing is reported, so none should be assumed.

The record lists no analyses in its analysis listing and does not report numerical results for the primary endpoint. It also does not report a missing-data method, rules for handling participants without complete follow-up, or sensitivity analyses. These omissions matter because the interpretation of an event count depends on who was observed and for what period. The primary analysis population is defined as enrolled participants who received at least one dose, while the safety results list 6 participants at risk. The record does not provide further detail about endpoint-specific denominators or missing observations.

The study is described as single-arm and open-label, with no randomization or control group. A comparative analysis between treatment groups is therefore not available. The registry record does not report a statistical analysis plan, a protocol-based sample-size justification, or interim analyses. These matters are unreported; they cannot be reconstructed from the listed outcomes or the safety counts.

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 safety results list 6 participants at risk in the PF-06741086 (marstacimab) 300 mg subcutaneous single-dose group. The record reports 0 with serious adverse events, 1 in the other adverse-event category, and 0 deaths. No serious-event terms are listed.

These are counts from the study group, not comparisons with another group. The registry record does not provide event terms for the participant in the other category, the event’s grade, timing, or investigator-assessed relationship to treatment. It also does not state in the safety results whether that event met the primary definition of a treatment-emergent adverse event. The primary endpoint result itself is not reported.

General statistical explanation: a zero count is an observation in a finite study group, not proof that the underlying event rate is zero. Likewise, the single other-event count does not by itself describe severity or causality. The adverse-event definition includes occurrences without regard to whether they were caused by study treatment, and treatment-related TEAEs were determined by the investigator.

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

The registry record documents a completed Phase 1, single-arm study of one 300 mg subcutaneous dose of PF-06741086 in Chinese adults with severe hemophilia. It reports a limited set of safety counts: 0 serious adverse events, 1 participant in the other adverse-event category, and 0 deaths among 6 participants at risk. These observations describe what the record lists for this group.

The record does not report the primary endpoint result, which was the number of participants with treatment-emergent adverse events from Day 1 to Day 42. The separate safety counts cannot be used to fill that gap. The record also lists pharmacokinetic and pharmacodynamic aims, but does not report numerical results for the listed concentration-time or pharmacokinetic outcomes. Thus, the outcome names indicate what was to be assessed, not what was observed.

The study does not show a treatment contrast because it had no control group and no randomized allocation. Its results cannot establish how the observed counts or any unreported measures compare with another treatment, no treatment, or usual care. The record also does not establish causation for adverse events: the adverse-event definition does not require a causal relationship, and the more specific treatment-related assessment was made by investigators.

General statistical explanation: conclusions depend not only on the observed data but also on design, measurement, analysis, and uncertainty. A small single-arm record can describe observations in its enrolled group, but it cannot by itself provide a controlled estimate of a treatment effect. The absence of reported events in a category is not proof that the event cannot occur. Here, the lack of a primary-endpoint result and the absence of numerical pharmacokinetic findings further limit interpretation.

Accordingly, the defensible reading is narrow: the registry describes the study design and reports the specified safety counts. It does not report enough outcome information to characterize the primary endpoint or the listed pharmacokinetic results, and it does not support comparative or causal conclusions.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the limits and uses of a small, single-arm Phase 1 design. Its stated aims combine safety and tolerability with pharmacokinetic and pharmacodynamic characterization after a single subcutaneous dose. In that setting, descriptive summaries can be useful for recording observed events and characterizing measured concentration patterns, provided the results and analysis details are available.

The registry record makes the design constraints explicit: there was no randomization, no masking, and no control group. These features determine what kinds of conclusions can be drawn. A count in the intervention group is not a treatment-versus-control effect estimate. General statistical reasoning also emphasizes that sparse event counts carry substantial uncertainty, even when the observed count is zero.

The record illustrates why endpoint definitions and endpoint results must be distinguished. It defines treatment-emergent adverse events and a Day 1 to Day 42 assessment period, but does not report the primary endpoint count. Safety counts are listed separately and cannot be treated as a substitute. Similarly, naming pharmacokinetic outcomes does not reveal their measured values or precision.

Finally, the study record shows why sample-size planning illustrations require careful labeling. Hypothetical calculations based on stated assumptions do not reveal the original protocol rationale, do not describe the actual single-arm design when they assume two arms, and are not observed power. The protocol’s sample-size justification and statistical plan are not reported in the registry record. Keeping these distinctions clear helps prevent descriptive safety information, planning assumptions, and comparative evidence from being conflated.

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 central limitation for interpreting outcomes is that the registry record does not report the primary endpoint result. Although the endpoint is defined as the number of participants with treatment-emergent adverse events during Day 1 to Day 42, the result cannot be recovered from the separately listed serious and other adverse-event counts. The record also does not provide numerical findings for the pharmacokinetic measures or pharmacodynamic outcomes described as study aims.

The design is single-arm, open-label, non-randomized, and non-controlled. There is no concurrent comparator to support a between-group estimate, and knowledge of treatment was not masked. These design features limit causal interpretation and may affect event reporting or assessment. The study concerns one dose and a specified population, so the registry description should not be generalized to other populations, regimens, or settings without evidence beyond this record.

The safety record lists 6 participants at risk, with 0 serious adverse events, 1 participant in the other category, and 0 deaths. It does not give the event term, grade, timing, or relationship assessment for the other event, nor does it list serious-event terms. It does not report an uncertainty interval for these counts. A zero count in this observed group does not demonstrate that the underlying event risk is zero.

The record does not report a statistical analysis plan, a protocol-based sample-size justification, missing-data methods, endpoint-specific denominators, interim analyses, or a multiplicity strategy. It lists 54 outcome measures and no analyses in its analysis listing. Without the missing results and methods, the precision and completeness of the reported outcome information cannot be evaluated further.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate Safety and Tolerability of a Single Dose of PF-06741086 in Chinese Adult Participants With Severe Hemophilia — NCT04878731.
• Registry record last updated 2023-07-07; status last verified 2022-08.
• Results first posted 2023-07-07.
• 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 describes NCT04878731 as a completed Phase 1, multicenter, single-arm, open-label, non-randomized, non-controlled study of PF-06741086 in Chinese adults with severe hemophilia. The intervention was one 300 mg subcutaneous dose. Enrollment was 6; the study start date was 2021-04-16, and the primary completion date was 2021-08-10.

The primary endpoint was the number of participants with treatment-emergent adverse events from Day 1 to Day 42. Its result is not reported in the registry record. Safety results list 6 participants at risk, 0 with serious adverse events, 1 in the other adverse-event category, and 0 deaths. Secondary outcomes include marstacimab concentration and pharmacokinetic measures, but numerical results for those outcomes are not reported in the record.

The single-arm design supports description of the recorded group, not a controlled treatment comparison. The registry record does not report the statistical analysis plan or sample-size justification.