This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Plerixafor Versus G-CSF in the Treatment of People With WHIM Syndrome (NCT02231879), a randomized phase 2, phase 3 study. The primary outcome is Severity of Infection.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02231879 |
| Phase | Phase 2, Phase 3 |
| Condition | Myelokathexis, Infections, Neutropenia |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Quadruple |
| Enrollment | 20 |
| Arms in the primary outcome | 2 |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
Population
People with WHIM syndrome and a CXCR4 gene mutation were eligible; the stated age range was 10-75. WHIM syndrome is described in the registry record as a rare disease associated with warts, hypogammaglobulinemia, infections, and myelokathexis. The record lists 20 participants enrolled and states that 19 started both treatment periods.
Intervention
Plerixafor was given by subcutaneous injection twice daily. The treatment comparison concerned infection severity during a 12-month treatment period on each study drug. Both study drugs were described as being given twice daily for 14 months in the arm descriptions.
Comparator
The active comparator was granulocyte colony stimulating factor, abbreviated G-CSF. Participants received the two study drugs in different treatment orders: plerixafor followed by G-CSF, or G-CSF followed by plerixafor.
Primary question
The trial asked whether infection severity differed between treatment periods, using a Total Infection Severity Score (TISS) that sums severity scores for infections and weights them based on time at risk. The primary analysis was based on the difference between period scores, with special rules for drug failures. The registry record does not report the resulting primary comparison estimate or its uncertainty.
This is an active-treatment comparison, not a comparison against no treatment. The crossover design means treatment order matters when interpreting the primary outcome: the score difference is defined as period 1 minus period 2, and a higher difference means a worse outcome in the first period. The record describes the question and analysis rules, but does not state a primary-analysis result that would establish the size or precision of any difference.
3. Trial Design
The registry describes a randomized, quadruple-masked crossover study with phase listed as both Phase 2 and Phase 3. The two treatment orders were plerixafor followed by G-CSF and G-CSF followed by plerixafor. Participants therefore served as their own comparison across the two treatment periods, while randomization determined treatment order. The registry record reports enrollment of 20.
The brief design description includes an initial period, an adjustment period, and two treatment years. It says participants began twice-daily G-CSF injections, with dose decided by their doctors, and continued usual antibiotics and/or immunoglobulin. The description also mentions blood testing, health diaries, clinic visits, and an evaluation before switching treatment. Both study drugs are described in the arm information as subcutaneous injections given twice daily for 14 months. The primary endpoint, however, refers to scores from 12 months of treatment on each drug. The registry record does not explain the relationship between these stated durations.
The stated primary endpoint compares infection severity across treatment periods. Nineteen participants started both periods. The registry record also reports drug failures in both periods for 1 participant and drug failure only during the plerixafor period for 3 participants. These failures matter because the primary analysis had predefined rules for incorporating them rather than treating all period scores as ordinary observed scores.
The registry record does not report details of the randomization procedure, allocation concealment, masking roles, crossover sequence balance, or a washout interval. It also does not report the planned sample-size justification or a fuller statistical analysis plan. Those details should not be inferred from the designation of the trial as randomized, masked, or crossover.
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
| Stage | Plerixafor First Then Filgrastim | Filgrastim First Then Plerixafor |
|---|---|---|
| STARTED | 10 | 9 |
| COMPLETED | 8 | 7 |
| NOT COMPLETED | 2 | 2 |
Reasons for not completing this period:
| Reason | Plerixafor First Then Filgrastim | Filgrastim First Then Plerixafor |
|---|---|---|
| Adverse Event | 2 | 1 |
| Lack of Efficacy | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: There are 19 participants that started both periods, 1 participant had drug failure during both periods, 3 participants had drug failure only during the period on Plerixafor. The outcome measure data table only summarizes the periods that were not drug failures, but the primary analysis includes the treatment failure periods by giving them the most extreme score (see Statistical Analysis section).
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.
| Characteristic | Unit | Plerixafor First Then Filgrastim | Filgrastim First Then Plerixafor | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 9 | 19 | |
| Age, Categorical: <=18 years | Participants | 1 | 4 | 5 |
| Age, Categorical: Between 18 and 65 years | Participants | 9 | 5 | 14 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 8 | 5 | 13 |
| Sex: Female, Male: Male | Participants | 2 | 4 | 6 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 8 | 7 | 15 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 1 |
| Region of Enrollment: United States | participants | 8 | 7 | 15 |
| Region of Enrollment: El Salvador | participants | 1 | 0 | 1 |
| Region of Enrollment: Sweden | participants | 1 | 0 | 1 |
| Region of Enrollment: Spain | participants | 0 | 2 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Severity of Infection, measured over Scores from 12 months treatment on each study drug.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | score on a scale (with no maximum) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the Total Infection Severity Score (TISS), intended to summarize infection burden and severity over treatment with each study drug. Each infection during the stated 12-month treatment period was assigned a severity score on a scale from 1 to 10, with higher scores representing more severe infections. The scores were summed and weighted based on time at risk to produce a period-level TISS. The registry describes the score range as 0 to infinity, so the endpoint has no fixed maximum.
This kind of composite score can represent more than the occurrence of an infection alone: it incorporates the severity assigned to infections and accounts for time at risk. That is a general rationale for using a severity score when the clinical question concerns the burden of infection, rather than simply whether any infection occurred. The record does not report how severity ratings were assigned in practice, who assessed them, or whether assessors followed a specified adjudication procedure.
The primary analysis was defined using the difference in TISS between period 1 and period 2. A higher difference means a worse outcome in period 1 than in period 2. Drug failure was predefined as more extreme than any TISS score; when failure occurred in only one period, the difference was assigned the highest absolute value, with its sign determined by treatment order. This approach makes the handling of failure part of the endpoint definition, not merely a missing-score convention.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The reported period-level summaries are medians and full ranges. For G-CSF, the registry reports a median TISS of 12.5, with a range from 0 to 36, based on 18 participants in the outcome summary. For plerixafor, it reports a median of 9.0, with a range from 0 to 24, based on 15 participants. These summaries describe the periods included in the outcome measure data; the registry states that periods with drug failure are not included in that summary.
Those medians are not the primary crossover comparison. The primary analysis uses within-participant period differences and includes special assignments for drug failures. Comparing the two medians as if they were a randomized parallel-group contrast would disregard the paired structure, treatment order, and failure rules. The different numbers included in the two period summaries also mean that they do not describe precisely the same set of periods. The registry record does not report a primary difference estimate, confidence interval, or p-value, so the magnitude and precision of the primary contrast cannot be assessed from these summaries.
The full ranges indicate that observed scores varied across the summarized periods, including scores at 0 and substantially higher values. A range describes the observed extremes; it does not show how scores were distributed between those extremes or how precisely a treatment contrast was estimated. A median is a measure of the middle of the observed values, not a mean, and does not itself quantify uncertainty around a paired treatment effect.
Drug failures are especially important to interpretation. The record states that 1 participant had failure during both periods and 3 had failure only during the plerixafor period. The primary analysis treated failures according to prespecified rules, but the outcome summary excluded periods that were failures. Therefore, the period-level medians should not be read as containing the same failure information as the primary analysis.
In sum, the registry reports descriptive TISS summaries for periods not classified as failures and describes how the primary analysis was constructed. It does not report the primary analysis result or uncertainty, so the posted statistics do not establish the size, direction, or precision of the primary treatment comparison. No conclusion about treatment benefit should be drawn from the medians alone.
9. Statistical Methods Explained
Why does a crossover design change the comparison?
In a crossover trial, each participant receives more than one treatment in sequence. The statistical comparison can therefore use the participant's outcomes under both treatments, rather than treating the treatment groups as entirely separate sets of people. In general, this can account for stable differences between participants, because the comparison is within the same person. It also makes treatment sequence and period important: outcomes can vary over time, and a preceding treatment may affect a later period. These are general features of crossover studies, not claims about effects that occurred in this trial.
The registry says treatment order was randomized and describes two orders: plerixafor then G-CSF, and G-CSF then plerixafor. It does not report the sequence allocation details or whether a washout interval was used. Without the primary analysis results and fuller design details, the period summaries cannot show whether period or sequence effects influenced the comparison.
What does the TISS summarize?
Each infection during the stated treatment period received a severity rating on a scale of 1 to 10. The ratings were summed and weighted based on time at risk. The resulting TISS was a period-level score, with higher infection ratings contributing to a higher score. This is a composite way to summarize infection experience: it combines information about severity and the amount of time at risk, rather than reporting only a count of infections.
As a general statistical point, a score that can extend without a fixed maximum may have a skewed distribution, particularly when many observations are low and a smaller number are high. A median and full range can describe the center and extremes without assuming a symmetric distribution. They do not, however, provide an estimate of the paired treatment difference or its uncertainty. The registry reports medians and ranges for periods not classified as drug failures, while the primary analysis is based on period differences.
How are failures incorporated?
The registry defines drug failures as more extreme than any TISS score. If failure occurred in only one period, the primary analysis assigned the difference the highest absolute value and used treatment order to determine its sign. This means that the primary analysis was designed to account for these failures as outcomes, rather than simply omitting the participant or treating the score as an ordinary observed TISS. The registry's description does not give the numerical assigned values or a complete account of how participants with failure in both periods contributed to the analysis.
General principle: explicit failure rules can preserve a clinically meaningful distinction between an observed score and a period in which treatment failed. They also influence the estimand—the particular treatment contrast the analysis aims to describe. Because the assigned values and full primary analysis results are not reported in the registry record, the resulting effect cannot be reconstructed from the period-level medians.
What do the descriptive statistics say about uncertainty?
A median is the middle observed value when data are ordered. A full range gives the lowest and highest observed values. Neither is a confidence interval. In general, a confidence interval expresses the precision of an estimate under a statistical model: a narrower interval indicates greater precision, while a wider interval indicates more uncertainty. No confidence interval for the primary comparison is reported in the registry record.
For the outcome summaries, the registry reports 18 G-CSF periods and 15 plerixafor periods, excluding periods that were drug failures. Because the endpoint is based on a crossover, paired observations are central to the primary comparison; these counts do not reveal which participants contributed to both descriptive summaries. A direct subtraction of the medians would not recreate the median or mean of within-participant differences and would not incorporate the failure rules.
What analysis details remain unknown?
The registry record does not report the test or model used for the primary comparison, the confidence level or interval method, the handling of any other incomplete observations, or adjustments for period or sequence. It also does not report an analysis population definition beyond the stated information about participants who started both periods and the drug failures. No assumption about a particular statistical test, model, or treatment of missing data should be made in the absence of those details.
The study lists two outcome measures and three analyses, but does not report how those analyses relate to one another or whether a multiplicity procedure was used. In general, multiplicity arises when several statistical hypotheses are tested, because repeated testing can increase the chance of at least one false-positive finding. Whether that issue was addressed, and how, is not reported in the registry record. The record also gives sample-size planning assumptions for an illustration, but does not report the trial's own design justification or a primary-analysis result to which such planning can be compared.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures and three analyses, while reporting no secondary outcomes in the posted results. It does not explain how the analyses correspond to the outcome measures, which analysis was designated for each, or whether any were exploratory. A multiplicity adjustment or testing hierarchy is not reported in the registry record. In general, when several hypotheses are tested, the chance of at least one false-positive result can increase; prespecified priorities or adjustment methods can address that issue. No claim can be made about how multiplicity affected this trial without the analysis plan and results.
Some information about the analysis population is reported. The registry states that 19 participants started both treatment periods, that 1 participant had drug failure in both periods, and that 3 had failure only during the plerixafor period. It says the outcome measure data summary includes periods that were not drug failures, while the primary analysis includes the failure handling described for the period difference. The remaining description of the analysis population is incomplete in the registry record. It does not report a complete participant flow, the treatment-specific analysis denominators for the primary comparison, or how participants who did not start both periods were handled.
The exclusion of failure periods from descriptive summaries is distinct from their inclusion under special rules in the primary analysis. The record does not describe how any other missing or incomplete TISS data were treated, whether missingness differed by treatment or period, or whether sensitivity analyses were conducted. These details matter because missing-data assumptions can affect an estimate, particularly when the reason for missingness is related to health status or treatment experience. The missing-data plan and any sensitivity analysis results are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| G-CSF | 6 | 19 | 31.6% |
| Plerixafor | 2 | 19 | 10.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| G-CSF | 0 of 19 |
| Plerixafor | 0 of 19 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| G-CSF | 19 of 19 |
| Plerixafor | 19 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | G-CSF | Plerixafor |
|---|---|---|---|
| Arthritis | Musculoskeletal and connective tissue disorders | 1 of 19 | 1 of 19 |
| Flu-like illness | Infections and infestations | 1 of 19 | 0 of 19 |
| pneumonia | Infections and infestations | 1 of 19 | 0 of 19 |
| Urinary tract infection | Infections and infestations | 1 of 19 | 0 of 19 |
| Appendicitis | Infections and infestations | 1 of 19 | 0 of 19 |
| Cellulitis | Infections and infestations | 0 of 19 | 1 of 19 |
| Transient ischemic attack | Nervous system disorders | 1 of 19 | 0 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | G-CSF | Plerixafor |
|---|---|---|---|
| Bone pain | Musculoskeletal and connective tissue disorders | 14 of 19 | 7 of 19 |
| Acute bronchitis | Infections and infestations | 9 of 19 | 2 of 19 |
| Upper Respiratory Tract Infection | Infections and infestations | 5 of 19 | 6 of 19 |
| Headache | Nervous system disorders | 6 of 19 | 3 of 19 |
| Nausea | Gastrointestinal disorders | 6 of 19 | 1 of 19 |
| Otitis media | Infections and infestations | 6 of 19 | 1 of 19 |
| Weight gain | Investigations | 2 of 19 | 5 of 19 |
| Hyperuricemia | Metabolism and nutrition disorders | 4 of 19 | 3 of 19 |
| Knee pain | Musculoskeletal and connective tissue disorders | 5 of 19 | 2 of 19 |
| Gastroenteritis | Infections and infestations | 6 of 19 | 0 of 19 |
Serious events with the highest arm-level rate: flu-like illness (5.3%), arthritis (5.3%), pneumonia (5.3%), urinary tract infection (5.3%), appendicitis (5.3%).
The registry reports serious adverse events for the two treatment groups separately. For G-CSF, 6 of 19 participants were affected by a serious adverse event; for plerixafor, 2 of 19 were affected. The record lists no deaths in either group. It also reports that other, non-serious adverse events affected 19 of 19 participants in each group. These are participant counts as presented in the registry, not event totals.
The listed serious adverse event terms each have a reported frequency of 5.3%: flu-like illness, arthritis, pneumonia, urinary tract infection, appendicitis, and cellulitis. The record does not clarify whether people could be counted under more than one term or explain the relationship between these terms and the participant-level serious-event counts. Such terms should not be summed to infer a number of affected participants.
General interpretation: adverse-event counts describe events recorded during the study, but a difference in counts alone does not establish that a treatment caused an event or that the treatments differ in safety. This was a crossover study, and the adverse-event summary is not the primary TISS comparison. The registry does not report exposure-adjusted rates, event timing, severity details beyond the serious-event classification, or a statistical comparison of safety outcomes. These safety figures should therefore be read as descriptive registry summaries, not as a standalone causal comparison.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this randomized crossover study was designed to compare infection severity during treatment with plerixafor and G-CSF in people with WHIM syndrome. It defines a TISS based on the severity of infections and time at risk, and it describes a primary analysis using within-participant period differences with explicit rules for drug failures. The record also provides medians and ranges for periods without drug failure.
Those descriptive summaries are not the primary treatment-effect estimate. The median TISS was 12.5 for G-CSF and 9.0 for plerixafor in the reported period summaries, with different numbers of periods included. The registry does not report the primary difference estimate, its confidence interval, or a p-value. Consequently, the posted information does not establish the size, direction, or precision of the primary comparison. It also does not support treating a difference between the displayed medians as the trial's paired treatment effect.
The registry's failure rules are part of the analysis definition and could affect the primary result. The descriptive summaries exclude failed periods, while the primary analysis incorporates failure information according to the stated rules. This distinction means the summaries cannot be used to infer how the primary analysis would turn out.
The record describes serious adverse events and other adverse events, but these are descriptive counts and are not a substitute for the infection-severity analysis. Neither the efficacy summaries nor the adverse-event counts alone establish a causal treatment effect. The statistical interpretation remains limited by the absence of the primary analysis result and its uncertainty, as well as unreported details about the analysis methods, missing data, and multiplicity.
13. Why This Trial Matters Statistically
This trial raises statistical issues that are particularly relevant when a clinical comparison uses a crossover design and an endpoint that includes treatment failure. A crossover comparison can use outcomes from both treatment periods within a participant, but the treatment sequence and period structure must be respected. A summary that compares group-level medians does not automatically preserve that paired structure.
The TISS combines infection severity with time at risk. That gives the endpoint a broader interpretation than a simple infection count, while also making the score distribution and analysis rules important. A score with no fixed maximum may not behave like a normally distributed measurement. In general, skewness and unusually high values can affect which summary and analysis methods are appropriate. The registry reports medians and ranges, but does not report the primary model or test, so the method used to account for the endpoint's distribution cannot be assessed.
The explicit treatment-failure rules also matter. They make failure part of the primary outcome comparison, rather than allowing the analysis to rely only on observed TISS scores. At the same time, the registry's descriptive summaries omit failed periods. Keeping those two forms of reporting distinct is essential to avoid interpreting the medians as a complete account of the primary endpoint.
Finally, statistical evidence is not communicated by a point summary alone. A primary estimate together with an uncertainty interval would help readers assess both the direction and precision of the comparison. The registry record does not report those results. This illustrates why a detailed endpoint definition is valuable but cannot replace the numerical primary analysis and its uncertainty when interpreting a trial.
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 principal limitation for statistical interpretation is that the registry record describes the primary endpoint and analysis rules but does not report the primary comparison estimate, confidence interval, or p-value. The period-level medians and ranges are descriptive summaries for periods without drug failure; they do not provide the paired treatment contrast or its precision.
The registry states that participants with drug failure were handled specially in the primary analysis, but the available description does not fully specify the assigned values or explain the contribution of participants with failure in both periods. The reported analysis-population description is also incomplete. The record does not provide a full participant flow or account for all incomplete outcome data.
Details needed to evaluate the crossover analysis are not reported, including the randomization procedure, sequence balance, any washout interval, and the statistical method for accounting for treatment period or sequence. The record also does not report how TISS severity scores were assessed, whether outcome assessment was independent or adjudicated, or the basis for choosing the primary analysis method.
The treatment-duration descriptions differ: the endpoint refers to 12 months on each drug, while the arm descriptions state that both study drugs were given for 14 months. The registry record does not explain this difference. It also does not report the trial's sample-size justification, a multiplicity plan, or sensitivity analyses for missing data and drug failure. These omissions limit assessment of the assumptions behind the primary comparison and the robustness of any result.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Plerixafor Versus G-CSF in the Treatment of People With WHIM Syndrome — NCT02231879.
- Registry record last updated 2026-06-26; status last verified 2026-06.
- Results first posted 2023-04-07.
- 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.
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18. Record Summary
The registry describes a completed randomized, quadruple-masked crossover study of plerixafor versus G-CSF in people with WHIM syndrome. It lists Phase 2 and Phase 3, enrollment of 20, and two treatment orders. The primary endpoint was infection severity summarized as TISS over a 12-month period on each drug, with a primary analysis based on period differences and special rules for drug failures.
The posted outcome summaries give medians and full ranges for periods not classified as failures: 12.5, range 0 to 36, for G-CSF and 9.0, range 0 to 24, for plerixafor. The registry also reports serious and other adverse-event counts. It does not report the primary analysis estimate or its uncertainty, and several details about analysis methods, missing data, and crossover procedures are not reported in the registry record.