Extension Study of Subcutaneous Immunoglobulin Human in Patients With Primary Immunodeficiency (PID): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extension Study of Subcutaneous Immunoglobulin Human in Patients With Primary Immunodeficiency (PID) (NCT00719680), a na phase 3 study. The primary outcome is Annualized Rate of Serious Bacterial Infection (Intention-to-Treat Population).

2. Clinical Question

This is an extension study of IgPro20 in primary immune deficiency, rather than a trial that directly compares the treatment with a concurrent control. Its clinical question is therefore descriptive: how often serious bacterial infections occurred over the recorded exposure to study medication. The planned observation period was for the duration of the study, up to approximately 104 weeks. The registry does not report how long each participant was followed or the total exposure time used in the endpoint calculation.

The endpoint concerns a defined set of acute serious bacterial infections: pneumonia, bacteremia or septicemia, osteomyelitis or septic arthritis, bacterial meningitis, and visceral abscess. It is not a measure of every infection or of all aspects of health. The listed secondary outcomes address broader infection rates, immunoglobulin G serum trough levels, effects of infection on daily activities, hospitalization, antibiotic use, and adverse events. The record does not provide the primary endpoint result, so it cannot answer how high the observed rate was or how precisely it was estimated.

3. Trial Design

The registry identifies NCT00719680 as a Phase 3, multicenter extension study of IgPro20 in subjects with primary immune deficiency. CSL Behring is listed as the sponsor. The study began in 2008-06, reached primary completion in 2010-06, and is recorded as completed. Enrollment is listed as 21.

The design is recorded as single-group. Allocation is marked NA, and masking is recorded as none. The intervention is IgPro20, a biological product administered subcutaneously. The dose was to be the same as in the previous pivotal study ZLB04 009CR (NCT00419341), given weekly or twice a week. For twice-weekly dosing, the description specifies half of a weekly dose at each administration. The registry does not describe a concurrent control group, so the design does not support a like-for-like treatment comparison.

The primary endpoint is the annualized rate of serious bacterial infection in the intention-to-treat population, with units of infections per subject year. The registry defines this population as all subjects treated with study medication during any study period. The endpoint description says that the rate was based on the total number of infections and total subject study days in the analysis population, adjusted to 365 days. The stated timeframe was for the duration of the study, up to approximately 104 weeks.

Secondary outcomes include annualized rates of any infection and hospitalization due to infection, total IgG trough levels, infection-related days away from work, school, kindergarten, day care, or normal activities, antibiotic use, and adverse events classified by relatedness and severity. The registry lists 17 outcome measures overall. It does not report the protocol’s detailed statistical plan, eligibility criteria, follow-up completeness, or the results for the primary endpoint.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Intention-to-Treat (ITT) population comprised all subjects treated with study medication during any study period.

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 Annualized Rate of Serious Bacterial Infection (Intention-to-Treat Population), measured over For the duration of the study, up to approximately 104 weeks.

The primary endpoint is the annualized rate of serious bacterial infection, measured in infections per subject year. It is intended to describe how frequently specified serious infections occurred relative to the time participants were observed. The registry defines acute serious bacterial infections as pneumonia, bacteremia or septicemia, osteomyelitis or septic arthritis, bacterial meningitis, and visceral abscess.

Using subject time in the denominator is useful when participants contribute different amounts of follow-up. A simple event count alone would not distinguish a group observed for a short period from a group observed for longer. Annualization expresses the event rate on a common time scale. The registry says the calculation used the total number of infections and total subject study days for the analysis population, with adjustment to 365 days.

This rate is a group-level summary, not a statement that each participant experienced the same frequency of infection. It also does not, by itself, describe the severity or duration of every infection, nor does it cover infections outside the specified serious bacterial categories. The registry does not report the calculated rate, the event count used, the total subject study days, or a confidence interval. Consequently, the endpoint’s observed magnitude and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a rate, not a simple proportion of participants with an event. A rate relates event occurrence to accumulated time at risk or under observation. This is useful when people contribute different lengths of follow-up, because the denominator reflects exposure time rather than treating every participant as if observed for an identical duration. In this record, the endpoint is expressed as infections per subject year.

The registry describes the calculation as the total number of infections divided in relation to the total number of subject study days in the analysis population, then adjusted to 365 days. This is the registry’s stated approach. It does not post the event total, the total subject study days, or the resulting annualized rate. Without those values, the numerical calculation cannot be checked or interpreted from the record. The endpoint is also restricted to the specified acute serious bacterial infections, not all infections.

Why use an annualized rate?

In general, an annualized rate puts observed events on a common exposure-time scale. A participant followed for less time contributes less observed time than a participant followed longer. This can make a rate more informative than a raw event count when follow-up varies. However, a rate is still a summary of the group’s observed events and exposure. It does not imply that events occur at a constant pace for every individual, and it does not show how event risk changes over time.

Rate analyses can also be affected by variation in event counts between participants. In general, a simple count model may be too restrictive if the observed counts vary more than its assumptions allow; this is called over-dispersion. Methods that account for over-dispersion can change estimated uncertainty. The registry record does not report the model used to estimate the primary endpoint’s uncertainty, whether over-dispersion was assessed, or whether any model-based adjustment was made. No particular model should therefore be attributed to this analysis.

What does an uncertainty interval add?

In general, a confidence interval gives a range of values compatible with the data under the assumptions of the statistical method. Its width conveys precision: a wider interval indicates less precise estimation, while a narrower interval indicates greater precision. It does not show the range of individual participants’ outcomes. No confidence interval for the primary rate is reported in the registry record. A p-value, hypothesis test, or other inferential result for this endpoint is also not reported there.

The intention-to-treat population is defined in the registry as all subjects treated with study medication during any study period. This definition identifies the stated analysis population, but it does not reveal how many participants contributed endpoint data, whether all available follow-up was included, or how missing observations were handled. The registry does not report those details. In a single-group study, an intention-to-treat label does not create a control comparison; it describes which treated subjects belong to the stated population.

How does the design shape inference?

General statistical interpretation depends on the design as well as the endpoint. This study is recorded as single-group, with allocation marked NA and masking marked none. A rate estimated within that group can describe the observed experience over the recorded study exposure. It cannot alone estimate a contrast with a concurrent control. A causal treatment comparison generally requires a suitable comparison design and an analysis that reflects it; neither a control group nor a comparative effect estimate is reported in this record.

The registry lists 17 outcome measures, including the primary endpoint and secondary outcomes. Multiple outcomes can raise multiplicity questions because drawing conclusions from many tests may increase the chance of at least one apparently notable result under a null situation. In general, statistical plans can address this through prespecified hierarchies or other adjustments. The registry record does not report a multiplicity strategy or inferential results for the listed outcomes. It also reports zero analysis records, so the posted record does not provide analysis-level results to evaluate.

The registry lists a study duration up to approximately 104 weeks for the primary endpoint timeframe, but does not report participant-specific follow-up or exposure time. That distinction is important for a rate: the planned observation window is not equivalent to the actual denominator used. The absence of the denominator, event count, estimate, and uncertainty measure prevents a reader from independently evaluating the primary rate’s calculation, stability, or precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures, covering the primary serious bacterial infection rate and secondary outcomes such as any infection, IgG trough levels, infection-related disruption of activities, hospitalization, antibiotic use, and adverse events. When a study examines multiple outcomes, multiplicity can matter for inferential claims: testing many hypotheses may increase the chance of a result appearing notable by chance. General approaches include prespecified ordering of outcomes or adjustment of statistical thresholds, but the registry record does not report whether either approach was planned or used. It also does not report the statistical analysis plan or inferential results for the outcomes.

The record lists zero analysis records. That means no analysis-level results are posted in the registry record; it does not establish what analyses may have been conducted outside the registry. For the primary endpoint, the event count, total subject study days, annualized rate, and uncertainty estimate are not reported.

The intention-to-treat population is defined as all subjects treated with study medication during any study period. This is the only stated analysis-population definition in the primary endpoint description. The record does not say how missing endpoint information was handled, whether participants withdrew, whether follow-up was incomplete, or whether any sensitivity analyses were performed. It does not report missing-data assumptions or imputation methods. These omissions limit assessment of whether the posted population definition and available follow-up fully support the intended rate calculation.

11. 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: cellulitis (4.8%), pneumonia (4.8%), thyroid cancer (4.8%), diarrhea (4.8%).

The registry’s adverse-event information lists the IgPro20 group with 21 participants at risk for serious adverse events and 4 affected. For other adverse events, it lists 21 at risk and 21 affected. These are descriptive counts from the single-group study, not comparisons against a control group. The record does not report deaths; the death value is not reported in the registry record.

The listed serious adverse event terms are cellulitis, pneumonia, thyroid cancer, and diarrhea, each recorded at 4.8%. The registry does not give event counts for these individual terms in the information, so the percentages should not be translated into additional counts. The record also does not describe event timing, duration, recurrence, relatedness, or severity for each listed term. The secondary outcome list refers to adverse events by relatedness and severity, but the registry record does not provide a full analysis of those dimensions.

These safety figures do not establish a comparative risk, because no control group is listed. They also do not answer the primary efficacy question, which concerns the annualized rate of serious bacterial infection. The serious adverse event category and the endpoint’s serious bacterial infection definition are distinct measures; the posted record does not establish that every listed adverse event corresponds to a primary endpoint infection.

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

The record establishes that the study evaluated subcutaneous IgPro20 in a single-group extension study involving people with primary immune deficiency. It specifies an annualized rate of serious bacterial infection as the primary endpoint, defines the infection categories included, and describes use of subject study days to calculate the rate. It also records secondary outcomes and selected adverse-event counts.

The record does not report the primary endpoint’s numerical rate, event total, exposure-time denominator, confidence interval, or test result. It therefore does not show how frequently serious bacterial infections occurred in the analysis population or how precisely that frequency was estimated. The endpoint definition and calculation description explain what was intended to be measured, but they are not a result.

The single-group design further limits what could be concluded even if a rate were posted. A rate from the treated group would describe observed events relative to observed exposure. Without a concurrent comparator, it would not quantify a treatment contrast or establish that the treatment caused any observed pattern. The registry record does not report a causal comparative estimate.

The adverse-event counts provide a limited descriptive safety account: 4 of 21 participants at risk are listed as affected by serious adverse events, and 21 of 21 are listed as affected by other adverse events. These counts do not provide a comparison with another treatment, and the event-term percentages do not supply the missing primary endpoint result. No deaths are reported in the registry record’s available entry.

Accordingly, the defensible interpretation is about what the study set out to measure and what the registry posts, not about an unreported efficacy result. Conclusions about the magnitude, precision, or comparative meaning of the primary endpoint cannot be drawn from this record alone.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between defining an endpoint and reporting its result. The registry gives a clear rate-based primary outcome, identifies the infection categories included, and describes an exposure-time denominator. Those details help readers understand the intended estimand: event frequency relative to study time in the treated population.

At the same time, a rate’s interpretation depends on its numerator, denominator, and uncertainty. The registry does not report the serious infection count, total subject study days, calculated rate, or confidence interval. Without them, a reader cannot assess the event frequency, precision, or sensitivity to the amount of follow-up. The planned timeframe of up to approximately 104 weeks does not replace actual exposure information.

The single-group design is another important statistical feature. It supports description of the observed treated group, but it does not provide a like-for-like control comparison. This distinction prevents a within-group event rate from being mistaken for a comparative effect. Allocation is marked NA and masking is none, so the registry does not describe randomized or masked treatment assignment.

The record also illustrates why outcome lists and analysis results should be distinguished. It lists 17 outcome measures, but reports zero analysis records. Names of outcomes indicate what was tracked, not what was observed. Likewise, selected adverse-event counts give descriptive safety information but cannot fill the gap in the primary endpoint result. These features make the study’s statistical contribution difficult to evaluate beyond its design, endpoint definition, and reported safety counts.

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 interpreting this specific registry entry is that the primary endpoint result is not reported in the registry record. The event count, total subject study days, annualized rate, and confidence interval are absent. Without these, the endpoint’s magnitude and precision cannot be assessed, and its calculation cannot be independently checked.

The design is recorded as single-group, with allocation marked NA and masking marked none. No concurrent comparator is listed. The study therefore does not provide a like-for-like control comparison in the registry record, limiting interpretation to description of the treated group rather than a comparative estimate.

The registry reports enrollment of 21 and defines the intention-to-treat population as all subjects treated with study medication during any study period. It does not report how many participants contributed primary endpoint data, individual follow-up, total exposure time, withdrawals, or missing outcome information. The stated timeframe of up to approximately 104 weeks does not establish the actual observation time contributed by participants.

The record lists 17 outcome measures but zero analysis records. It does not report the detailed statistical analysis plan, methods for handling multiple outcomes, missing-data procedures, or model used for the rate analysis. The adverse-event entry provides selected counts and serious event terms, but does not report deaths, event timing, or detailed relatedness and severity results. These omissions constrain interpretation of both efficacy and safety information in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Extension Study of Subcutaneous Immunoglobulin Human in Patients With Primary Immunodeficiency (PID) — NCT00719680.
• Registry record last updated 2014-04-02; status last verified 2012-12.
• Results first posted 2013-01-25.
• 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

NCT00719680 is a completed Phase 3, multicenter, single-group extension study sponsored by CSL Behring. It evaluated subcutaneous IgPro20 in people with primary immune deficiency, with enrollment recorded as 21. The study began in 2008-06 and reached primary completion in 2010-06.

The primary endpoint was the annualized rate of serious bacterial infection in the intention-to-treat population, expressed as infections per subject year. The registry describes a calculation using total infections and total subject study days, adjusted to 365 days, but does not report the resulting rate or its precision. The record lists 17 outcome measures and zero analysis records.

For the IgPro20 group, the registry lists 4 participants affected by serious adverse events among 21 at risk and 21 affected by other adverse events among 21 at risk. The primary endpoint result is not reported in the registry record, and the single-group design has no listed concurrent comparator.