Pharmacokinetics of Sotrovimab as Pre-exposure Prophylaxis for COVID-19 in Hematopoietic Stem Cell Transplant Recipients, COVIDMAB Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics of Sotrovimab as Pre-exposure Prophylaxis for COVID-19 in Hematopoietic Stem Cell Transplant Recipients, COVIDMAB Study (NCT05135650), a na phase 1 study. The primary outcome is Half-life of Sotrovimab (VIR-7831) Post-transplant.

2. Clinical Question

This is a pharmacokinetic question, not a randomized comparison of sotrovimab against another treatment or no treatment. Pharmacokinetics describes how a drug is absorbed, distributed, metabolized, and eliminated. The study’s listed secondary outcomes include comparisons of half-life or exposure across specified participant groups, as well as breakthrough SARS-CoV-2 acquisition, antibody clearance, anti-drug antibodies, and adverse events. The record does not provide numerical results for those outcomes either. Its summary describes a possible rationale for studying sotrovimab, but that rationale is not evidence of a clinical benefit. The central statistical interpretation is consequently about what the study set out to estimate and what the registry actually reports, rather than about an effect on infection or recovery.

3. Trial Design

The registry identifies this as a phase I, single-group study with an enrollment of 20 and a status of terminated. It lists Fred Hutchinson Cancer Center as the sponsor. The study start is recorded as 2022-01-25, and primary completion as 2022-10-18. The reason for termination is not reported in the registry record; status alone does not establish why the study stopped or whether any particular result was obtained.

Participants in the prevention arm receive sotrovimab intravenously over 30 minutes within 1-7 days before pre-transplant conditioning begins. Blood and nasal swab sample collection takes place during the trial. Questionnaire administration is also listed as an intervention. Masking is listed as none, and allocation is not applicable. Because the study has a single group, it does not provide a concurrent control group for a treatment comparison. The listed enrollment should not be mistaken for a count of participants with complete endpoint data; completion and analysis counts are not reported in the registry record.

The primary outcome is post-transplant sotrovimab half-life, measured in days over a timeframe of up to 24 weeks. The record describes descriptive statistics from estimation using a population pharmacokinetic model. It also lists secondary outcomes covering half-life or exposure in selected subgroups, breakthrough infection, serum or plasma antibody clearance, anti-drug antibodies, and adverse events. The record lists 10 outcome measures and 0 analyses. Those entries do not supply numerical findings, subgroup estimates, or details about which outcomes were successfully analyzed.

Planning illustrations based on an observed effect are distinct from the study’s actual design. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe hypothetical planning calculations, not the single-group enrollment or allocation used in this study. The registry record does not report a sample-size justification or the protocol’s statistical plan.

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

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 Half-life of Sotrovimab (VIR-7831) Post-transplant, measured over Up to 24 weeks.

The primary endpoint is the half-life of sotrovimab, identified as VIR-7831, after transplantation. Half-life describes the time associated with a drug concentration declining by half under a specified pharmacokinetic model. It is used to characterize drug persistence and elimination, rather than to measure infection prevention or another direct clinical benefit. The endpoint is expressed in days, and the planned timeframe is up to 24 weeks.

The registry describes estimating the endpoint with a population pharmacokinetic model and reporting descriptive statistics of the model estimation. It also notes that VIR-7831 levels can be measured with an idiotypic antibody assay that is not affected by COVID-19 infection or vaccination. This assay detail concerns measurement of the drug level; it does not establish the precision or completeness of the endpoint data.

The record does not report a half-life estimate, its standard deviation, a confidence interval, or the number of participants contributing to the estimate. It specifies a mean and standard deviation as the endpoint summary, but does not provide their numerical values. Consequently, the endpoint’s magnitude and precision cannot be assessed from the registry results. A planned measurement and analysis description should not be read as a reported pharmacokinetic finding.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a population pharmacokinetic model and descriptive statistics for the primary half-life endpoint. It does not report the model specification, estimation procedure, covariates, diagnostic checks, or numerical estimates. The explanations below distinguish the general statistical ideas from the methods actually documented for this study.

What does a population pharmacokinetic model do?

General: A population pharmacokinetic model represents concentration measurements over time and describes patterns shared across participants as well as variation between participants. It can use measurements taken at different times and can account for the fact that an individual’s concentration profile is observed only through collected samples. A model may estimate population-level parameters, individual-level values, or both, depending on its specification. These general features do not establish which particular model choices were made in this study. The registry record says only that the half-life will be estimated from a population pharmacokinetic model; further model details are not reported in the registry record.

A model-based estimate is not necessarily a direct calculation from a single observed concentration pair. Its interpretation depends on the model’s assumptions, sampling schedule, measurement quality, and fit to the data. Those details matter because different choices can affect the estimated concentration-time pattern and the resulting half-life. The registry record does not provide enough information to evaluate those components or the model’s adequacy.

What does half-life represent?

General: Half-life is a pharmacokinetic summary of how quickly a drug concentration declines in the body under a model of drug disposition. It is not itself a measure of clinical protection, infection, recovery, or safety. The registry identifies post-transplant half-life as the primary endpoint and expresses it in days. It does not give a numerical estimate, so readers cannot determine the observed duration or compare its precision across populations from the record.

The record names the endpoint summary as a mean with standard deviation. General: The mean describes the center of a set of values, while the standard deviation describes their spread around that center. These summaries answer different questions: a mean is not a measure of precision, and a standard deviation is not a confidence interval. The registry does not report either numerical summary for the primary endpoint. It also does not report a confidence interval or another uncertainty measure.

What role does the assay play?

The registry states that VIR-7831 levels can be measured using an idiotypic antibody assay that is not affected by COVID-19 infection or vaccination. This is a description of the intended measurement method. It does not provide information about assay precision, detection limits, quality-control procedures, or the amount of missing assay data. Those items are not reported in the registry record.

How should subgroup outcomes be understood?

The listed secondary outcomes include half-life in matched versus mismatched donors, half-life in autologous versus allogeneic transplantation, and exposure in participants with versus without diarrhea or graft versus host disease. General: Subgroup comparisons describe whether estimated outcomes differ across categories of participants. Their interpretation depends on how the groups are defined, how many observations contribute to each estimate, and whether the analysis accounts for relevant differences between groups. The registry record does not provide subgroup estimates, group sizes, or the methods for those comparisons. No conclusion about a subgroup difference can be drawn from the outcome titles alone.

The record also lists outcomes concerning breakthrough SARS-CoV-2 acquisition, antibody clearance, anti-drug antibodies, and adverse events. Their presence in the outcome list indicates planned measurement, not a reported finding. Numerical results and analysis details for these outcomes are not reported in the registry record.

What does a confidence interval add?

General: A confidence interval describes statistical uncertainty around an estimate under a specified analysis. A narrower interval indicates greater precision under that method, while a wider interval indicates less precision. It does not by itself show that an estimate is clinically important or unbiased. No confidence interval for the half-life estimate is reported in the registry record, so its precision cannot be judged from such an interval.

Why can over-dispersion matter?

General: Over-dispersion occurs when observed variation is greater than a statistical model expects. If it is not handled appropriately, uncertainty estimates can be too small and comparisons can appear more precise than the data support. This is a general consideration rather than a reported feature of this study. The registry does not describe a model assessment for over-dispersion or indicate whether it was relevant.

What do the planning assumptions mean?

The stated sample-size illustration assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. These are planning assumptions, not a description of the actual single-group design. General: Sample-size planning asks how much information a hypothetical study might need to detect a specified effect under specified assumptions. It is not the same as estimating the observed effect, and a planning calculation is not observed power. The registry record does not report a sample-size justification for the actual study or give the numerical inputs and outputs for any planning illustration. Since the primary result is not reported, planning values based on an observed effect cannot establish the precision of this study’s estimate.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Sotrovimab")
n   <- c(20)
m   <- c(51.14)
sp  <- c(18.59)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Sotrovimab  20  51.140  18.590  42.440  59.840

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures, including the primary half-life endpoint and secondary pharmacokinetic, infection, antibody, and adverse-event outcomes. It lists 0 analyses. These entries do not establish that each outcome was measured or analyzed, nor do they provide results. Numerical findings for the primary and secondary outcomes are not reported in the registry record.

When a study evaluates multiple outcomes or subgroup comparisons, the chance of at least one apparently unusual finding can increase. General: Multiplicity methods can address this issue by controlling error rates or by clarifying that analyses are exploratory. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or whether subgroup analyses were prespecified. It is therefore not possible to determine how multiple questions were handled statistically.

The record does not report missing-data counts, reasons for missingness, or how incomplete measurements were handled. It also does not state how many participants contributed to the primary endpoint estimate, define an analysis population, or describe exclusions from analyses. Enrollment and the listed risk counts do not establish completeness of pharmacokinetic sampling or follow-up. The record’s primary endpoint timeframe is up to 24 weeks, but participant-level follow-up completeness is not reported.

The study status is terminated, but the reason and the relationship, if any, between termination and data availability are not reported in the registry record. The protocol’s statistical analysis plan, interim analyses, and sample-size justification are also not reported. These gaps limit assessment of outcome selection, missing-data bias, and the relationship between planned and completed analyses.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (5.0%).

The registry lists 20 participants at risk in the Sotrovimab group for serious adverse events and 20 at risk for other adverse events. It reports 1 participant with a serious adverse event, 3 participants with other adverse events, and 1 death. The listed serious adverse event term is Death, with a value of 5.0%.

These entries are descriptive counts, not a comparison with a control group. The single-group design supplies no concurrent comparator for assessing whether event frequency differed from what would otherwise have occurred. The registry record does not report event timing, causes, severity details beyond the serious-event listing, attribution to treatment, or participant-level overlap between event categories. It also does not provide detailed definitions or follow-up information for these safety summaries.

Accordingly, the entries document what the registry reports but do not establish causation. The presence of a death in the safety record does not by itself show that sotrovimab caused it, and the absence of further detail cannot be treated as evidence about the nature of the event. The registry record does not report a fuller safety analysis.

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

This study addresses a pharmacokinetic question: the post-transplant half-life of sotrovimab in hematopoietic stem cell transplant recipients. The registry describes a model-based approach and specifies the endpoint’s units and timeframe. It does not report a numerical half-life estimate or a measure of its uncertainty. The posted results therefore do not establish the magnitude or precision of the primary endpoint.

The study is single-group, so it is not a randomized treatment comparison and has no control group described in the record. Even if a half-life estimate were available, that estimate would characterize drug disposition in the analyzed participants; it would not by itself show that sotrovimab prevents SARS-CoV-2 infection, changes recovery, or improves another clinical outcome. The registry’s summary gives a possible rationale for studying the drug, but a rationale is not a result.

The registry lists secondary outcomes that could address subgroup pharmacokinetics, breakthrough infection, antibody clearance, anti-drug antibodies, and adverse events. Numerical findings for these outcomes are not reported in the registry record. The listed safety counts are descriptive and, without a comparator and further event details, cannot establish a treatment effect or a causal relationship.

The registry reports an enrollment of 20 and a terminated status. Those details do not reveal the number with complete pharmacokinetic data, the reason for termination, or whether the primary analysis was completed. Those details are not reported in the registry record. The record also does not report the protocol’s statistical plan, missing-data methods, or model diagnostics. Readers should distinguish the study’s objectives and planned measurements from numerical findings: the former are documented, while the primary result needed to assess the central pharmacokinetic question is not reported.

14. Why This Trial Matters Statistically

Pharmacokinetic studies can characterize how a drug behaves in a population for whom drug exposure is of interest. In this study, the registry identifies hematopoietic stem cell transplant recipients and a post-transplant sotrovimab half-life endpoint. A population pharmacokinetic model is the stated approach, making details about measurements, model assumptions, and uncertainty important to interpretation.

The statistical question is narrower than whether a treatment prevents infection or changes clinical outcomes. Half-life is a drug-disposition measure. It can inform understanding of exposure over time, but it is not itself evidence of clinical benefit. The registry separately lists outcomes such as breakthrough SARS-CoV-2 acquisition and adverse events, but does not report numerical findings for them. Keeping pharmacokinetic and clinical outcomes distinct prevents a mechanistic measurement from being mistaken for a demonstrated clinical effect.

The single-group design also matters. Without a like-for-like control group, the record cannot support a controlled estimate of treatment differences. Its stated planning illustration assumptions include equal allocation between two arms, but those assumptions are hypothetical and do not describe the actual study design. Planning calculations should not be confused with observed results or observed power.

Finally, the record’s lack of numerical primary results illustrates why an endpoint definition is not a finding. The study description explains what was intended to be estimated; it does not let readers judge the estimate’s size, variability, or precision. Reporting model estimates, uncertainty, analysis populations, and missing-data handling would be necessary to assess the statistical evidence behind the pharmacokinetic question. These details are not reported in the registry record.

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.

The main limitation for interpreting this registry record is that the numerical primary endpoint result is not reported. The record specifies a mean and standard deviation for the half-life summary and describes model-based estimation, but provides neither value. It also does not report a confidence interval or other estimate of uncertainty. As a result, the primary pharmacokinetic finding and its precision cannot be assessed.

The single-group design does not include a like-for-like control comparison. It can describe outcomes in the study group, but cannot separate changes associated with sotrovimab from other influences through a randomized comparison. The record does not report participant-level pharmacokinetic sampling, the number contributing to the primary estimate, or completeness of follow-up over the stated timeframe of up to 24 weeks.

Important model details are not reported in the registry record, including the model specification, estimation methods, covariates, diagnostics, and handling of incomplete observations. Assay precision and data-quality procedures are also not described. The record lists several subgroup and secondary outcomes but does not provide their estimates, analysis methods, or any multiplicity approach.

The study is marked terminated, but the reason is not reported. The registry does not report the protocol’s statistical analysis plan, sample-size justification, or whether interim analyses were conducted. The listed safety counts lack event timing, causes, attribution, and detailed follow-up context. These limitations do not show that the study lacked data or that its methods were inadequate; they identify information that is not reported in the registry record and that is needed for fuller statistical interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacokinetics of Sotrovimab as Pre-exposure Prophylaxis for COVID-19 in Hematopoietic Stem Cell Transplant Recipients, COVIDMAB Study — NCT05135650.
• Registry record last updated 2025-02-13; status last verified 2025-02.
• Results first posted 2025-02-13.
• 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.

19. Record Summary

The registry describes a phase I, single-group study of sotrovimab pharmacokinetics in hematopoietic stem cell transplant recipients. The listed enrollment is 20, and the status is terminated. Participants receive sotrovimab intravenously over 30 minutes within 1-7 days before pre-transplant conditioning, with blood and nasal swab collection during the trial.

The primary endpoint is post-transplant half-life, expressed in days and estimated using a population pharmacokinetic model, with a timeframe of up to 24 weeks. The registry record does not report a numerical estimate or uncertainty measure. It lists 10 outcome measures and 0 analyses.

Safety entries include 1 participant with a serious adverse event, 3 with other adverse events, and 1 death; the serious-event term Death is listed as 5.0%. The reason for termination, analysis population, missing-data handling, model details, and numerical findings for the primary and secondary outcomes are not reported in the registry record.