Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency (NCT00520494), a na phase 4 study. The primary outcome is Proportion of Patients Achieving Immunoglobulin G (IgG) Levels ≥ 5 g/L on Day 12.

2. Clinical Question

The clinical question is about reaching a defined laboratory threshold at a specified time, rather than about a comparison of treatment effects between groups. The registry also lists later IgG threshold outcomes, change from baseline, infection rate, trough levels, and concentrations of specific IgGs as secondary outcomes. Their results are not reported in the registry record. The record describes a 25-week observation period, but does not report the primary endpoint estimate or its confidence interval. Consequently, the clinical question can be described from the stated objective and endpoint, but the posted record does not provide the outcome data needed to assess how often the threshold was reached.

3. Trial Design

This was a Phase 4, single-group study of Vivaglobin in previously untreated patients with primary immunodeficiency. The registry lists an enrollment of 18 and a completed status. The study began in 2007-03, and primary completion was recorded as 2008-10. These record dates describe the study timeline; they do not supply evidence about the endpoint results.

All participants were assigned to the Vivaglobin group, with no separate control arm. Allocation is listed as not applicable, and masking is listed as none. The registry therefore does not describe random assignment or blinding. Without a concurrent comparison group, changes or outcomes observed during follow-up cannot be separated from other influences by a between-group treatment contrast.

The intervention description specifies Vivaglobin as a 16% (160 mg/mL) liquid formulation of human IgG for subcutaneous use. The loading regimen was 100 mg/kg on 5 consecutive days. The maintenance regimen was 100 mg/kg 1 to 2 times a week for 24 weeks. The study objective describes an observation period of 25 weeks.

The primary endpoint was the proportion of patients achieving IgG levels of at least 5 g/L on Day 12. Its stated analysis population was the intention-to-treat data set, defined in the registry as all patients who were treated with the study drug and completed Day 12. Although 18 participants were enrolled, the number who met that endpoint population definition is not reported in the registry record. Nor does the record report the endpoint numerator, proportion, or confidence interval. The study design and measurement plan are therefore identifiable, but the posted record does not support a quantitative conclusion about the primary outcome.

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) data set comprised all patients who were treated with the study drug and completed Day 12.

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 Proportion of Patients Achieving Immunoglobulin G (IgG) Levels ≥ 5 g/L on Day 12, measured over On Day 12.

The primary endpoint is the proportion of patients whose immunoglobulin G (IgG) level reached at least 5 g/L on Day 12. It is a binary outcome at the participant level: each patient either meets the stated threshold at the specified time or does not. The endpoint then summarizes the share of the analysis population that met that criterion.

A threshold-based endpoint offers a direct way to describe whether a prespecified laboratory level was attained at a particular time. In this study, Day 12 was selected to address the stated objective of assessing an early response after the loading regimen. The endpoint is not a measure of change in symptoms, infection prevention, or long-term clinical benefit; those questions require outcomes that directly capture those domains. The registry separately lists infection rate and later IgG measurements as secondary outcomes.

The primary endpoint specifies a 95% confidence interval as its dispersion measure. In general, a confidence interval conveys the statistical uncertainty around an estimated proportion; a narrower interval indicates greater precision, while a wider interval indicates less precision. The interval’s endpoints and the estimated proportion are not reported in the registry record, so the precision of the observed result cannot be assessed from this record.

The registry defines the primary analysis population as treated participants who completed Day 12. The number of participants meeting that definition is not reported in the registry record. Enrollment alone does not establish the endpoint denominator, and the endpoint result should not be inferred from the enrollment count.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a proportion, because the registry classifies it as the percentage of participants with an event. In this setting, the event is reaching the specified IgG threshold on Day 12. Each participant contributes to the count of those meeting the threshold or those not meeting it, subject to the analysis population definition. The proportion is an estimate of how common threshold attainment was in that study population; it is not itself a comparison with another treatment.

What does the confidence interval convey?

The registry names a 95% confidence interval as the dispersion measure for the primary endpoint. In general, a confidence interval expresses uncertainty around an estimate that arises from observing a sample rather than every person in the broader population of interest. The point estimate gives the observed proportion, while the interval indicates a range of values compatible with the data under the statistical method used. A confidence interval does not remove uncertainty, prove a result is clinically important, or establish a causal effect.

Neither the primary proportion nor its confidence interval is reported in the registry record. The precision of the primary estimate therefore cannot be judged. The enrollment count of 18 is not enough to recover the confidence interval, because the primary analysis population is defined by treatment and Day 12 completion, and the number meeting that definition is not reported.

Why does the analysis population matter?

The registry defines the intention-to-treat data set for the primary endpoint as all patients who were treated with study drug and completed Day 12. This is the operational population stated for the outcome. It is important to read that definition directly: enrollment, receipt of treatment, and completion of the Day 12 assessment are not interchangeable. The record does not report the number included in this data set or explain how any missing Day 12 measurements were handled.

In general, missing outcome measurements can affect both the estimate and its interpretation, especially when the likelihood of missingness is related to a participant’s condition or experience. Statistical approaches can include assumptions or procedures for handling missing observations, but a particular approach should not be attributed to this trial unless it is reported. Missing-data methods are not reported in the registry record.

How should the single-group design be understood?

A single-group design describes outcomes among participants receiving the study intervention. Because the registry lists no comparator group, it does not provide a contemporaneous estimate of outcomes under an alternative condition. General statistical interpretation distinguishes a within-group description from a between-group contrast: the former says what was observed in the group; the latter estimates how outcomes differ between groups. Only the former design structure is described.

Masking is listed as none. In general, masking is intended to reduce the influence of knowledge about treatment assignment on behavior, measurement, or assessment. The registry does not report masked outcome assessment or another blinding procedure. This design feature should be considered when interpreting outcomes, but the record does not establish that it caused any particular bias.

What do the planning calculations represent?

Planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe participants per arm for 80% power, with the effect to detect expressed as a stated fraction of the observed effect. The assumptions are a planning framework, not a description of the study’s actual design: this trial is single-group, not an equal-allocation two-arm comparison. These illustrations are not observed power and do not show the probability that the trial’s actual result was correct. The registry does not report a sample-size justification for the trial itself.

In general, sample-size planning depends on the effect chosen for detection, variability or event rates, the significance level, and the desired power. A planning result is conditional on those assumptions; it is not an outcome observed in participants. Since the record does not report a primary estimate, the clinical meaning of any planning illustration cannot be assessed from the registry results.

What does the absence of analyses mean?

The record lists 20 outcome measures and 0 analyses. This means that the registry material does not provide analysis entries from which to inspect an estimated treatment effect, statistical test, or associated uncertainty for those outcomes. It does not establish that no analyses were conducted outside the registry. The statistical analysis plan, including any model choice, covariate adjustment, interim analysis, or multiplicity procedure, is not reported in the registry record.

In general, multiplicity refers to the increased chance of at least one apparently notable result when many outcomes or comparisons are examined. Prespecified outcome hierarchies or adjustment methods can address that issue, but neither the planned approach nor the application of an adjustment is reported. The primary endpoint remains the designated primary measure in the registry, while the listed secondary measures should not be treated as confirmatory findings without posted results and analysis details.

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("Vivaglobin")
n      <- c(18)
events <- c(0)
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  Vivaglobin  18  0  0.0  0.0  18.5  -0.0  17.6  0.1  17.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures, including the primary Day 12 threshold outcome and secondary measures covering later IgG thresholds, change from baseline, infection rate, trough levels, and specific antibody concentrations. It lists 0 analyses. Numerical results for these measures, and the statistical procedures used to analyze them, are not reported in the registry record.

When multiple outcomes are assessed, general statistical practice recognizes a multiplicity issue: the chance of observing at least one seemingly notable result can rise as the number of analyses increases. Trial protocols may specify a primary endpoint, a testing hierarchy, or an adjustment procedure. The multiplicity approach for this study is not reported in the registry record, so no claim can be made about whether or how such an issue was addressed.

The primary analysis population is defined as treated patients who completed Day 12. The record does not give the number in that population or explain how missing Day 12 observations were handled. It also does not report imputation, sensitivity analyses, or other missing-data procedures. The listed enrollment of 18 should not be substituted for the unreported primary analysis denominator.

The registry’s analysis population definition is the only stated population detail for the primary endpoint. Other analysis populations, exclusions, or analysis-set rules are not reported in the registry record. Likewise, the statistical analysis plan, including any covariate adjustment, interim analyses, or prespecified treatment of secondary endpoints, is not reported. These gaps prevent a full assessment of how analysis choices might have influenced the reported findings; in this record, the findings themselves are also absent.

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: headache (5.6%), meningitis (5.6%), pyrexia (5.6%), vomiting (5.6%), pseudomonal bacteraemia (5.6%).

The adverse-event record lists 18 participants at risk for serious adverse events and 2 affected participants in the Vivaglobin group. It also lists 18 at risk and 14 affected for other adverse events. These are counts in the posted safety record, not comparative treatment effects. There is no control group in this study from which to estimate how these counts differ from another treatment or from no treatment.

The registry lists Headache, Meningitis, Pyrexia, Vomiting, Pseudomonal bacteraemia, and Haemophilus infection among the top serious adverse event terms, each at 5.6%. The record does not state whether participants could contribute more than one term, so these percentages should not be added or treated as distinct-patient proportions. The number of deaths is not reported in the registry record; a null entry should not be read as evidence that no deaths occurred.

In general, adverse-event counts describe events recorded during the study period and do not by themselves establish that the intervention caused an event. The available record does not provide a comparator, detailed event timing, severity gradations, or participant-level overlap. These safety figures should therefore be read as descriptive registry counts, not as proof of causation or as a comparative risk estimate.

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

The study asked whether previously untreated patients with primary immunodeficiency reached an IgG level of at least 5 g/L on Day 12 after starting a specified subcutaneous Vivaglobin regimen. The registry record identifies that question and defines the primary analysis population. It does not report the observed proportion or its 95% confidence interval. The primary outcome’s direction, magnitude, and precision therefore cannot be established from the record.

Even if a numerical proportion were available, a single-group study would describe the outcome in the treated participants rather than estimate a randomized contrast against another treatment or control. The design does not support attributing all observed outcomes to the intervention by comparison with an alternative. The registry’s lack of masking is another design feature relevant to interpretation, though it does not demonstrate that any particular result was biased.

The Day 12 threshold is a laboratory endpoint. It is not, by itself, evidence about infection outcomes, later antibody levels, or other clinical effects. Those topics appear among the listed secondary outcomes, but their numerical results are not reported in the registry record. No conclusion about those outcomes should be inferred from the study objective or endpoint list.

The safety record provides counts of affected participants and a list of serious-event terms, but no randomized comparator. These data can describe what was recorded in the study group; they cannot establish comparative safety or causal attribution. The serious-event terms do not establish the number of distinct participants affected by each term because overlap is not described.

Accordingly, the record supports a description of the trial’s design, regimen, endpoint, and recorded safety counts. It does not provide the primary efficacy result or the information needed to assess its precision. It also does not establish a treatment effect, comparative benefit, or comparative risk. Distinguishing those limits from the study’s stated aim is essential when interpreting the registry entry.

14. Why This Trial Matters Statistically

This trial illustrates why registry entries need to be read at two levels: the stated research question and the results actually reported. The endpoint is specific, with a defined IgG threshold and measurement time, and the primary analysis population has a stated definition. Yet without an estimate, denominator, or confidence interval, the statistical result cannot be evaluated. A clearly specified outcome is not the same as a reported finding.

The single-group design also makes the distinction between description and comparison especially important. A proportion among treated participants can characterize the study group, but it is not a randomized estimate of a difference between treatment options. Readers should not interpret the study objective as evidence that the endpoint was achieved, or as evidence that the regimen caused any observed change.

The record also lists multiple outcomes but provides 0 analyses. This is a practical reminder that outcome listings alone do not reveal the analytic strategy or results. Without posted estimates and details about missing data and multiplicity, readers cannot assess the precision or robustness of endpoint findings.

Finally, the planning illustrations use a hypothetical two-arm framework, while the actual trial is single-group. Understanding that distinction prevents planning calculations from being mistaken for the trial’s design, enrollment target, or observed power. The registry record is useful for identifying the intended question and design, but its missing outcome analyses sharply limit statistical interpretation.

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 primary limitation for interpreting efficacy is that the primary outcome result is not reported in the registry record. The numerator, analysis denominator, estimated proportion, and 95% confidence interval are absent. Although 18 participants were enrolled, the primary analysis population includes treated participants who completed Day 12, and its size is not given.

The study has a single-group design with no separate comparator, and masking is listed as none. The record therefore does not offer a randomized between-group contrast. Even a reported outcome proportion would need to be interpreted as a description of the treated group rather than a direct comparative estimate.

The registry describes a 25-week observation period and a loading and maintenance regimen, but detailed adherence, discontinuation, and follow-up information are not reported in the registry record. The handling of missing primary endpoint measurements is also not reported. These omissions limit assessment of who contributed data and how complete follow-up may have affected estimates.

The analysis plan, multiplicity procedures, interim analyses, and sample-size justification are not reported in the registry record. The planning illustrations use assumptions for a two-arm comparison, which differs from the single-group design recorded for this trial. They should not be treated as an account of the original design or as observed power.

Finally, the record lists adverse-event counts and serious-event terms but does not describe overlap between terms or provide a comparator. It does not report a death count. These safety details are therefore descriptive and incomplete for comparative or causal interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency — NCT00520494.
• Registry record last updated 2013-06-20; status last verified 2013-06.
• Results first posted 2013-05-03.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed Phase 4, single-group study of Vivaglobin in 18 previously untreated patients with primary immunodeficiency. The intervention used a subcutaneous loading regimen followed by maintenance dosing, with an intended observation period of 25 weeks. The primary endpoint was the proportion reaching IgG levels of at least 5 g/L on Day 12.

The primary population was defined as treated participants who completed Day 12. The endpoint estimate, its 95% confidence interval, and the number analyzed are not reported in the registry record. The record lists 20 outcome measures and 0 analyses; results for the secondary outcomes are also not reported.

Safety entries list 2 of 18 participants affected by serious adverse events and 14 of 18 affected by other adverse events. The study has no comparator group, and the registry lists no masking. These design and reporting features limit conclusions to describing the stated study question and recorded safety counts; the posted record does not provide a quantitative primary efficacy finding.