A Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Participants With Primary Immunodeficiency Diseases (PID): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Participants With Primary Immunodeficiency Diseases (PID) (NCT04346108), a non-randomized phase 3 study. The primary outcome is Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2.

2. Clinical Question

The study was designed to assess pharmacokinetics, safety and tolerability, and efficacy in Japanese participants with PID. Its primary endpoint is a laboratory measure of IgG concentration at trough during the weekly subcutaneous treatment period. It therefore describes measured drug-related antibody levels at a specified point in the dosing interval; it is not, by itself, a clinical outcome such as infection frequency or symptom change.

The treatment sequence included an initial IGIV period, followed by weekly IGSC, 20% for participants entering Epoch 2. A subset then received biweekly IGSC, 20% in Epoch 3. Since there was no randomized comparator, the primary question is about the observed concentration during Epoch 2, not whether IGSC, 20% produced a better outcome than another treatment. Numerical endpoint results are not reported in the registry record, so the size and precision of the measured trough concentration cannot be assessed from the record.

3. Trial Design

This was a Phase 3, open-label, non-controlled, multi-dose study. The registry describes its allocation as non-randomized and its model as single-group, with no masking. The study enrolled 17 participants and is listed as completed. The recorded start date is 2020-08-11 and the primary completion date is 2021-12-22.

Treatment was organized into three epochs. In Epoch 1, participants received IGIV at 200 to 600 mg/kg every 3 or 4 weeks for up to 13 weeks. In Epoch 2, participants who entered from Epoch 1 received IGSC, 20%, at 50-200 mg/kg once a week for up to approximately 24 weeks after Epoch 1. In Epoch 3, a subset received IGSC, 20%, at 100-400 mg/kg biweekly for up to approximately 12 weeks after Epoch 2. The registry summary describes the main aim as assessing baseline levels of IgG in blood after weekly and biweekly IGSC, 20% treatment.

The absence of randomization and a control group means that comparisons between treatment periods would not have the protections of a randomized, concurrent comparison. Changes across epochs could reflect differences in dosing schedules, time, participant selection, or other factors; the registry record does not establish how such influences were addressed. The design also means the treatment periods should not be read as independent parallel arms.

The registry lists pharmacokinetic, safety and tolerability, and efficacy aims, and includes 30 outcome measures and 17 analyses. The detailed statistical plan, including how the analyses were selected or prioritized, is not reported in the registry record. The record identifies the sponsor as Baxalta now part of Shire. Treatment for PID was described as being managed by each participant’s doctor according to usual clinical practice.

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: Participants diagnosed with primary immunodeficiency diseases (PID) received immunoglobulin administered intravenously (IGIV) in Epoch 1, followed by immunoglobulin administered subcutaneously (IGSC) 20% in Epoch 2 and then followed by Epoch 3 respectively for up to approximately 50 weeks.

Epoch 1 (13 Weeks)

Epoch 2 (24 Weeks After Epoch 1)

Reasons for not completing this period:

Epoch 3 (12 Weeks After Epoch 2)

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic Analysis Set (PKAS) 1 included all participants in the all-treated set who have had at least 1 evaluable serum IgG concentration value and have had no major protocol deviations or events that would affect the serum IgG concentration analysis results. Only PKAS 1 participants in Epoch 2 were analyzed for this outcome measure.

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: All-Treated Set included all enrolled participants who received at least 1 dose of study drug (IGIV or IGSC).

6. Primary Endpoint

The registry lists the primary outcome as Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2, measured over Epoch 2 (period 2): Up to 24 weeks.

The primary endpoint is total serum trough levels of IgG antibodies during period 2 of Epoch 2, measured in grams per liter (g/L). The timeframe is Epoch 2 (period 2), up to 24 weeks. A trough concentration is a measurement taken at the low point of a dosing interval, before the next dose; in general, such a measure describes the concentration maintained between doses. The registry record says that total serum trough levels were assessed during this period.

The endpoint is summarized as a geometric mean with a 95% confidence interval. In general, a geometric mean is useful for positive measurements that are skewed, because it summarizes values on a multiplicative scale rather than treating equal absolute differences as the central pattern. A confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. Its width helps readers judge how precisely the underlying value has been estimated; it does not mean that individual participants’ values fall within that interval.

The registry record describes the primary population as PKAS 1: participants in the all-treated set with at least 1 evaluable serum IgG concentration and without major protocol deviations or events that would affect the serum IgG concentration analysis. The description ends with a further restriction to participants in Epoch, but does not specify the remainder of that wording. Further population details are not reported in the registry record.

The numerical geometric mean and confidence interval for the primary endpoint are not reported in the registry record. Without those values, it is not possible to describe the observed concentration or the precision of its estimate. This endpoint measures serum IgG concentration; it does not directly quantify clinical outcomes such as infections, nor does its definition alone establish a treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as a geometric mean and specifies a 95% confidence interval. It does not state the computational details used to obtain the estimate, the interval method, or a statistical model. Those details are not reported in the registry record. The explanation below describes the general statistical concepts rather than asserting that a particular method was used in this study.

What does a geometric mean describe?

In general, a geometric mean summarizes positive measurements by taking their logarithms, averaging on that transformed scale, and converting the result back to the original scale. This approach is often useful when values are right-skewed or when relative changes are more meaningful than equal absolute changes. For example, a multiplicative shift treats proportional increases and decreases as the central comparison. This is a general explanation; the registry record does not specify whether the analysis used a log transformation or how it handled the measurements.

The geometric mean is not the same as the arithmetic mean. It can be less influenced by particularly large values when the data are skewed, but it still depends on the observed distribution and the analysis population. It also does not describe the range of individual participant concentrations. The registry record does not provide participant-level values or a distribution summary that would allow those features to be examined.

How should the confidence interval be read?

In general, a confidence interval conveys uncertainty in an estimated quantity under a specified analysis procedure. A narrower interval indicates greater precision than a wider interval, all else being equal. It does not describe the spread of individual observations, and it is not a guarantee that a particular interval contains the true value. Interpretation depends on the sampling and modeling assumptions used to construct it.

The registry record specifies a 95% confidence interval for the primary geometric mean, but does not report its bounds. Its width therefore cannot be judged, and the degree of precision cannot be described. The record also does not specify whether interval construction accounted for repeated measurements, any correlation within participants, or other features of the study data.

What does a trough measure contribute?

As a general pharmacokinetic concept, a trough concentration is measured near the end of a dosing interval, before the next dose. It can describe the low point of concentrations maintained under a particular dosing schedule. In this study, the primary endpoint refers to total serum IgG trough levels during period 2 of Epoch 2, when participants were assigned to weekly IGSC, 20% treatment as described in the registry. The endpoint is therefore tied to a treatment period and schedule; it is not a direct measure of clinical benefit or harm.

Other pharmacokinetic outcomes named in the registry address different aspects of concentration and exposure. AUC0-last summarizes exposure over a stated observation interval; maximum and minimum concentrations describe high and low measured levels; apparent clearance relates exposure to drug removal, with the precise interpretation depending on the pharmacokinetic model. These are general descriptions of the measures. The registry record does not give their numerical values or full analysis specifications.

What does the design allow the analysis to say?

In general, random allocation and a concurrent control group help distinguish treatment effects from differences that would have occurred over time or between groups for other reasons. This study is listed as non-randomized, non-controlled, and single-group. Its epochs are sequential treatment periods, so they should not be treated as independently randomized arms. Any difference between measurements across periods could reflect treatment schedule as well as time, participant selection, or other changes. How those possibilities were handled analytically is not reported in the registry record.

The registry describes a primary analysis population requiring at least 1 evaluable serum IgG concentration and the absence of major protocol deviations or events that could affect the concentration analysis. Restricting an analysis population in this way can help focus on participants with usable measurements, but it can also affect generalizability if exclusions relate to outcomes. The number included in PKAS 1 and the handling of missing data are not reported in the registry record.

The record lists a two-sided significance level of 0.05 among assumptions for planning illustrations, alongside equal allocation between two arms and a normal approximation. Those are described as planning illustrations based on the observed effect, not the study’s own design. They are not evidence that this single-group trial had a two-arm design or that it achieved a particular level of power. The detailed statistical analysis plan, including any testing procedure used for trial outcomes, is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 30 outcome measures and 17 analyses, including the primary endpoint and multiple pharmacokinetic outcomes. Secondary outcomes include total serum trough levels in Epoch 1, AUC0-last for total serum IgG and its subclasses, apparent clearance for total serum IgG and subclasses, maximum concentration for total serum IgG and subclasses, and minimum concentration for total serum IgG. These measures address related but distinct aspects of pharmacokinetics.

When many outcomes or analyses are considered, the chance of obtaining at least one apparently notable result can increase. In general, multiplicity methods can control that risk, but they may also affect how estimates and tests are interpreted. Whether the study used a multiplicity adjustment, a hierarchy of endpoints, or another approach is not reported in the registry record. The record also does not explain which of the listed analyses were confirmatory or exploratory.

Missing-data procedures are not reported in the registry record. The primary analysis population requires at least 1 evaluable serum IgG concentration and excludes participants with major protocol deviations or events that could affect the analysis, but the record does not say how many participants met that definition. It does not describe how missing concentration measurements, incomplete follow-up, or exclusions were handled, or whether any sensitivity analysis was conducted.

The registry record does not report interim analyses or the rules, if any, for stopping or changing the study. The full statistical analysis plan and additional details about analysis populations are not reported in the registry record. As a result, the potential effects of multiplicity, missing observations, and population selection on the reported analyses cannot be assessed from the registry information.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events and other adverse events separately for each epoch. For serious adverse events, it records 0 affected participants among 17 at risk in Epoch 1, 0 among 17 in Epoch 2, and 0 among 7 in Epoch 3. The registry lists 0 deaths in each epoch. It also lists no terms among the top serious-event terms.

For other adverse events, the record lists 11 affected participants among 17 at risk in Epoch 1, 16 among 17 in Epoch 2, and 3 among 7 in Epoch 3. These are epoch-specific counts. They should not be added together to describe a participant total, because participants could have contributed to more than one epoch. The figures also do not provide the types, severity, duration, or timing of the other adverse events.

In general, an observed count of zero serious events in a study does not establish that the risk is absent. Safety estimates are influenced by the number of participants observed, the time under observation, and how events are defined and recorded. The registry record does not give event-level details, exposure-adjusted rates, or a comparison group. These figures describe the recorded safety experience in the listed epochs, rather than establishing a comparative safety effect.

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

The study addresses pharmacokinetics and safety in Japanese participants with primary immunodeficiency diseases who received IGIV followed by subcutaneous IGSC, 20% treatment. Its primary endpoint was total serum trough levels of IgG antibodies during period 2 of Epoch 2, expressed as a geometric mean with a 95% confidence interval. The registry record does not report the numerical estimate or confidence interval, so the primary endpoint’s observed level and precision cannot be stated.

The study’s structure matters when interpreting its results. It was open-label, non-randomized, non-controlled, and single-group. It therefore does not provide a randomized comparison against an untreated group or another treatment. The treatment sequence and changes between epochs may be informative descriptively, but the registry record does not establish that any difference between periods was caused by a change in treatment schedule.

The safety record lists no serious adverse events and no deaths in the reported epochs. It also lists other adverse events in each epoch. These counts describe what was recorded for the study periods; without details on event type, severity, follow-up, and a concurrent comparison, they do not establish comparative safety or rule out uncommon events.

The record does not provide enough information to assess the numerical pharmacokinetic results, missing-data impact, or the analysis choices used across multiple outcomes. It also does not report a clinical efficacy estimate that would allow conclusions about infections or other patient-centered outcomes. The trial therefore documents an assessment of IgG concentrations and safety under specified dosing schedules, but the registry information does not establish the size of a treatment effect or support a controlled comparison.

In general, a laboratory concentration can be relevant to understanding exposure, but it should not be substituted for a clinical outcome. The meaning of an endpoint depends on its measurement, analysis population, uncertainty, and study design. Here, the missing primary estimate and the absence of a control group limit interpretation of both the magnitude of the measured concentration and any causal claim.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how pharmacokinetic endpoints can be defined in a sequential, single-group study. It specifies a primary measure, the total serum trough level of IgG antibodies during period 2 of Epoch 2, and identifies its summary as a geometric mean with a 95% confidence interval. Those details clarify the intended quantity, unit, analysis period, and population concept, even though the numerical result is not reported in the registry record.

The treatment periods also illustrate why design and analysis cannot be separated. Epoch 1 used intravenous infusions, while Epoch 2 and Epoch 3 involved subcutaneous dosing on weekly and biweekly schedules. Since there was no randomized control group, period-to-period observations cannot be interpreted as a controlled estimate of the effect of one schedule versus another. The structure is relevant to descriptive pharmacokinetics, but it places limits on causal comparisons.

The record also highlights the importance of complete outcome reporting. A geometric mean and confidence interval can communicate both the estimated concentration and its uncertainty, but without their numerical values readers cannot judge the magnitude or precision of the primary result. Likewise, listing multiple pharmacokinetic outcomes without the estimates and details of multiplicity handling leaves their joint interpretation uncertain.

Finally, the record distinguishes serious from other adverse events and reports events by epoch. That separation is useful for reading safety data, while the sequential design means epoch counts should be understood as period-specific rather than as independent groups. Taken together, the design and reporting features make the study’s statistical contribution dependent on descriptive pharmacokinetic assessment; they do not supply a controlled estimate of comparative treatment effect.

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.

A key limitation is that the numerical primary endpoint result is not reported in the registry record. Although the endpoint definition includes the summary measure, unit, timeframe, and confidence interval type, the estimate and interval bounds are absent. The resulting concentration level and precision cannot be evaluated. Numerical results for the listed secondary pharmacokinetic outcomes are also not reported in the registry record.

The study was non-randomized, non-controlled, single-group, and open-label. It therefore lacks a randomized concurrent comparator, and treatment periods cannot be interpreted as like-for-like arms. The registry record does not describe a method for separating treatment effects from time effects, participant selection, or other influences across the sequence of epochs.

The primary analysis population is defined in part by evaluability and the absence of major protocol deviations or events affecting the concentration analysis. The number included in that population, the reasons for exclusions, and the handling of missing measurements are not reported in the registry record. The description of the population ends with an additional restriction to participants in Epoch, but the remainder is not reported in the registry record.

The record lists 30 outcome measures and 17 analyses, but multiplicity procedures, outcome hierarchy, and the distinction between confirmatory and exploratory analyses are not reported in the registry record. The statistical analysis plan, including any modeling details and interim analyses, is also not reported in the registry record. Safety counts are presented by epoch, without event-level detail or a comparison group. These limitations mean the record supports only a restricted descriptive reading of the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Participants With Primary Immunodeficiency Diseases (PID) — NCT04346108.
• Registry record last updated 2024-03-22; status last verified 2023-09.
• Results first posted 2024-03-22.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT04346108 is a completed Phase 3, open-label, non-randomized, non-controlled study of IGIV and IGSC, 20% in Japanese participants with primary immunodeficiency diseases. The registry lists 17 enrolled participants. The study included an initial IGIV epoch, weekly subcutaneous treatment in Epoch 2, and biweekly subcutaneous treatment for a subset in Epoch 3.

The primary endpoint was total serum trough levels of IgG antibodies during period 2 of Epoch 2, summarized as a geometric mean with a 95% confidence interval in g/L over up to 24 weeks. Its numerical result is not reported in the registry record. The safety record lists 0 serious adverse events and 0 deaths in each epoch, alongside other adverse events recorded by epoch.

The non-controlled, sequential design does not provide a randomized comparative estimate. Details on the statistical analysis plan, missing-data handling, and multiplicity procedures are not reported in the registry record.