A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency (NCT01289847), a na phase 4 study. The primary outcome is Adverse Events.

2. Clinical Question

The record also describes secondary objectives of assessing safety and tolerability and comparing collected data with adult participants with primary immunodeficiency from the GMX01 study. The registry record does not report the details needed to assess how that comparison was planned or conducted, including whether the adult data were analyzed alongside the pediatric study results.

This is a question about the observed experience during treatment, not a randomized comparison of Gammaplex with another treatment or with no treatment. The single-group design can describe events recorded among participants in the study, but it cannot by itself separate the effects of treatment from other explanations for those events. The posted outcome count therefore needs to be read as a descriptive result from the enrolled study population, rather than as a direct estimate of a treatment contrast.

3. Trial Design

The registry identifies this as a Phase IV, multicenter, open-label study evaluating efficacy, safety and pharmacokinetics of Gammaplex in children and adolescents with primary immunodeficiency diseases. It is marked completed, with enrollment of 25. The record lists Gammaplex as the intervention and describes a single-group design. Allocation is not applicable, and masking is listed as none.

In a single-group study, participants receive the study intervention without a concurrent randomized control group. Open-label means the study is not masked. These design features matter when interpreting the results: the record can report what happened in the enrolled group during the treatment period, but it does not provide a randomized comparison that would address how outcomes might have differed under another assigned treatment.

The primary outcome timeframe is 12 months. The stated main objective is to determine efficacy by measuring the number of serious acute bacterial infections during treatment. Secondary objectives concern safety and tolerability and comparison with adult-subject data from the GMX01 study. Although the official title describes a multicenter study and evaluates pharmacokinetics, further details of the sites, dosing, visit schedule, pharmacokinetic analyses, and the adult-data comparison are not reported in the registry record.

The registry gives the enrollment figure but does not report a sample-size justification, recruitment or retention details, or a protocol-level account of the design choices. It also does not report whether any design changes occurred. Those details should not be inferred from the study being completed or from the number enrolled. The central design context for reading the primary result is that it is a 12-month observation in a single, unmasked group, rather than a treatment-versus-control estimate.

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: This was a Phase IV, multicentre, open-label, non-randomised study. All enrolled subjects received study medication.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT)

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 Adverse Events, measured over 12 months.

The primary endpoint is described as the number of participants with serious, acute, bacterial infections, used as a measure of efficacy. Its timeframe is 12 months, and its analysis population is identified as Intent to Treat. The outcome record labels the measure “Adverse Events,” while the description specifies serious acute bacterial infections as the event of interest. The description is the more informative guide to what the primary measure counts.

A participant count is a binary-outcome summary: each participant is classified according to whether the specified event occurred during the defined observation period. Such a count gives a direct description of the frequency of the recorded event in the study group. It does not, by itself, indicate how many episodes each affected participant experienced, when the events occurred, or the total event burden. Those details are not reported in the registry record.

Serious acute bacterial infections were selected as the efficacy measure because the stated main objective was to assess the number of these infections during Gammaplex treatment. In general, an outcome should be interpreted according to its event definition, observation period and analysis population. Here, the registry provides those elements at a high level, but does not report further operational criteria for classifying an infection as serious, acute or bacterial. The count should therefore be read as the registry’s reported endpoint, without assuming additional definitions or adjudication procedures.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a participant count for an event that can be classified as present or absent over a specified period. For the primary efficacy measure, the event is a serious acute bacterial infection and the period is 12 months. The registry identifies the analysis population as Intent to Treat. This means the endpoint is reported for the population named in the record; the registry does not provide further details about population membership, exclusions, or how missing outcome information was handled.

What does a participant count tell the reader?

A count communicates how many participants in the stated group had the specified event. The accompanying at-risk count provides the group size used for that event category. Together, these numbers describe the observed outcome in the study group. They do not describe event timing, repeated episodes, severity beyond the event definition, or the chance of an event outside the study. Those more detailed results are not reported in the registry record.

In general, binary-outcome analyses may estimate an event proportion and its uncertainty. A confidence interval is a range of values compatible with the data under the chosen statistical method; it helps readers judge how precisely the underlying event frequency has been estimated. The registry record does not report a confidence interval for this primary result. No interval should be inferred from the participant count alone, and no precision claim can be made beyond stating the observed count and at-risk count.

Why does the study design affect statistical interpretation?

In general, a randomized comparison estimates a difference between groups assigned to different interventions. This study is recorded as single-group, with no concurrent comparator and no masking. Its primary result is therefore a description of the Gammaplex group, not a randomized estimate of a difference in outcomes. A one-group count cannot answer what would have happened to those participants under another treatment or under a control condition.

The record identifies the study as open-label. In general, lack of masking can influence how outcomes are assessed or reported, particularly when judgments are involved. The registry does not describe endpoint adjudication or other safeguards for assessing infections. It would be inappropriate to assume either that assessments were independent of treatment knowledge or that they were biased; the relevant procedures are not reported in the registry record.

How should the posted planning illustrations be understood?

The planning illustrations are described as calculations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are planning scenarios for hypothetical two-arm studies, not a description of the single-group design in this trial. The stated effect to detect is a fraction of the observed effect. The illustrations are not observed power and do not show that the original study had a particular probability of detecting an effect.

In general, planning calculations depend on assumptions about the effect to detect, the analysis method, allocation and chosen error rate. Changing those assumptions can change the resulting sample-size estimate. The record does not report the study’s own sample-size justification, and the planning assumptions described for the illustrations should not be mistaken for protocol assumptions. The registry does not provide enough information to judge whether the enrolled sample was selected to achieve a particular precision or statistical power.

The record does not report a statistical model for the primary endpoint, a hypothesis test, an adjustment for covariates, or a method for handling repeated infections. It also does not report confidence intervals or p-values for the primary count. In general, repeated events can require methods that account for the fact that more than one event may occur in the same participant; a participant count does not capture that repeated-event structure. Since the posted primary measure is a count of participants with an event, it should not be interpreted as an analysis of the total number of infection episodes.

The listed serious adverse-event terms include left lower lobe pneumonia and Acute Gastroenterirtis (AGE), each with a posted value of 4.0%. These are event-term entries in the safety summary, not an estimate of the primary endpoint’s uncertainty. The registry does not specify in this record how terms were coded, whether a participant could contribute multiple terms, or the denominator used for those percentages. They should be read as the values attached to the listed terms, without attempting to reconstruct their derivation.

10. Exact Estimates for Each Arm

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

R code and output

arm    <- c("Gammaplex")
n      <- c(25)
events <- c(2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Gammaplex  25  2  8.0  1.0  26.0  2.2  25.0  2.4  25.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple outcome measures and secondary outcomes labeled “Therapeutic Efficacy.” Multiple outcomes create a multiplicity question: when several outcomes or tests are considered, the chance of finding an apparently notable result by chance can differ from that for a single prespecified test. In general, a statistical plan may address this through a hierarchy of outcomes or an adjustment procedure. Whether such a plan was used is not reported in the registry record.

The record identifies the primary endpoint and its timeframe, which helps distinguish it from the secondary objectives. However, it does not report a complete endpoint hierarchy, statistical testing sequence, multiplicity adjustment, or the analysis plan for the secondary outcomes. No p-values are posted in the registry record for interpretation, so there is no basis for explaining whether an adjustment changed any statistical conclusion.

The primary analysis population is named as Intent to Treat. The registry record does not report the operational definition used for that population or how participants with incomplete follow-up were handled. It also does not report missing-data counts, reasons for missingness, imputation methods, sensitivity analyses, or whether all enrolled participants contributed primary endpoint information. The at-risk count is reported as 25 for the primary serious-event category, but that alone does not describe follow-up completeness or the treatment of missing outcome data.

In general, missingness matters because conclusions can depend on whether unavailable outcomes are related to participants’ health or event status. Without information about missing data and the analysis procedures, the degree to which missingness could affect the reported count cannot be assessed. The record also does not report interim analyses or stopping rules. No assumptions about these procedures should be made from the completed status of the study.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: left lower lobe pneumonia (4.0%), acute gastroenterirtis (age) (4.0%).

The safety summary lists 3 participants affected among 25 at risk for serious events in the Gammaplex group. For other events, it lists 25 affected among 25 at risk. These are participant counts in separate adverse-event categories. They should be read as reported, rather than converted into additional percentages or treated as event counts: the summary does not state how many separate episodes occurred in each participant.

The primary efficacy endpoint also records serious acute bacterial infections, but it is specifically defined by that infection description. The safety summary’s serious-event category is not necessarily identical to the primary endpoint. The registry record does not clarify the overlap between the two summaries, so the figures should not be assumed to represent separate sets of participants or interchangeable outcomes.

The record lists left lower lobe pneumonia and Acute Gastroenterirtis (AGE) among the serious-event terms, each with a value of 4.0%. The registry does not explain the coding, denominator, or whether participants could appear under more than one term. These term-level values should not be used to derive a broader event rate or a comparison with another treatment.

With no concurrent control group, these counts describe safety events recorded during the study but do not estimate an excess risk attributable to Gammaplex. The record does not report comparative safety analyses or further details about event severity, timing, relatedness, or follow-up after treatment.

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

The posted results describe events recorded in a completed, open-label, single-group study of Gammaplex in children and adolescents with primary immunodeficiency. The primary endpoint was the number of participants with serious acute bacterial infections during 12 months. The record reports 3 affected participants among 25 at risk for this endpoint.

That result answers a descriptive question: how many participants in the study group were recorded as having the specified event during the stated period? It does not answer a comparative question about whether that count would have been higher or lower with a different intervention. Since no concurrent comparator group is listed, the study does not provide a randomized treatment contrast for the primary endpoint.

The count also does not, on its own, establish the precision of the underlying event frequency. No confidence interval or p-value for the primary result is reported in the registry record. Nor does the participant count describe the total number of infection episodes, the timing of events, or how events were distributed over follow-up. Further details about these features are not reported.

The safety summary gives separate participant counts for serious and other events, and the listed serious-event terms carry values of 4.0%. Those data can be described as recorded in the safety summary, but their relationship to the primary infection endpoint and the derivation of the term-level percentages are not explained in the registry record. They do not establish a comparative safety effect.

The record’s stated objective includes comparison with adult data from GMX01, but the methods and results of that comparison are not reported in the registry record. Overall, the posted figures are useful as a description of the study group and its recorded events. They should not be expanded into claims about comparative efficacy, causal effects, or outcomes beyond the defined study period.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between describing outcomes in a treated group and estimating a treatment effect. The registry reports a single-group study, so its primary count can document what was observed among participants during the defined treatment period. A randomized comparator would address a different statistical question: how outcomes differ between groups assigned to different approaches. That contrast is not available from this design.

The endpoint also makes the unit of analysis important. It counts participants with serious acute bacterial infections, rather than all infection episodes. A participant-level count is directly interpretable for the stated objective, but it does not convey repeated-event burden or event timing. Readers should match the interpretation to the outcome actually recorded.

The record shows why event definitions and labels deserve attention. The primary outcome is titled “Adverse Events,” while its description identifies serious acute bacterial infections as the efficacy measure. The safety summary separately presents serious and other adverse-event counts. Keeping these distinctions clear prevents a safety category from being mistaken for the specifically defined efficacy endpoint.

Finally, reporting precision and analysis details are central to statistical interpretation. The registry gives participant counts but does not report a confidence interval, a p-value, missing-data procedures, or the study’s own sample-size justification. These omissions limit what can be concluded about uncertainty and robustness. The planning illustrations are explicitly based on a hypothetical two-arm setup and should not be mistaken for observed power or the design of this single-group study.

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 efficacy is the absence of a concurrent comparator. With a single-group, open-label design, the posted infection count cannot establish how outcomes would have differed under another assigned treatment. The record also does not report the methods or findings of the stated comparison with adult subjects from GMX01, so that objective cannot be evaluated from the posted information.

The registry provides an event count and an at-risk count, but does not report a confidence interval, p-value, or other measure of uncertainty for the primary endpoint. It does not describe the operational criteria for a serious acute bacterial infection, any adjudication process, or how repeated infections were handled. The participant count therefore cannot be read as a total episode count or as evidence about event timing.

Further limitations concern the completeness of the analysis description. Missing-data procedures, follow-up completeness, the study’s own sample-size justification, and the detailed statistical plan are not reported in the registry record. The record names the Intent to Treat population but does not provide its operational definition. It also does not describe interim analyses or adjustments for multiple outcomes.

The safety summary lists serious and other event counts, but does not explain their relationship to the primary infection endpoint or provide details about event timing, relatedness, coding, or the denominator for the listed term percentages. The enrollment figure alone cannot resolve these uncertainties. The results should therefore be interpreted narrowly as the counts posted for this study, with no additional assumptions about analysis procedures or participant follow-up.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency — NCT01289847.
• Registry record last updated 2014-12-23; status last verified 2014-12.
• Results first posted 2014-12-23.
• 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 record identifies a completed Phase IV, multicenter, open-label, single-group study of Gammaplex in children and adolescents with primary immunodeficiency diseases. Enrollment was 25, with no concurrent comparator group listed. The primary outcome was the number of participants with serious acute bacterial infections over 12 months in the Intent to Treat population.

The posted primary result records 3 affected participants among 25 at risk. The safety summary separately lists 3 participants affected among 25 at risk for serious events and 25 affected among 25 at risk for other events. No comparative estimate or confidence interval for the primary endpoint is reported in the registry record. The results are descriptive of the study group and do not provide a randomized estimate of treatment effect.