A Study to Evaluate the Long-term Safety of TAK-771 in Japanese Primary Immunodeficiency Disease (PID) Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Long-term Safety of TAK-771 in Japanese Primary Immunodeficiency Disease (PID) Participants (NCT05513586), a na phase 3 study. The primary outcome is Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs).

2. Clinical Question

3. Trial Design

This was a Phase 3, open-label, non-controlled extension study of TAK-771 in Japanese participants with primary immunodeficiency disease. Its registry title describes the study as an evaluation of long-term safety. The study used a single-group design, with no randomized allocation and no masking. The registry lists an enrollment of 15 and a status of completed.

The study began on 2022-09-13, and the primary completion date is 2025-10-30. The brief summary says participants could have taken part in the previous study TAK-771-3004 and, if eligible for this extension, would receive TAK-771 after that study ended. It describes treatment for a total of 3 years and says the number of clinic visits depended on infusion cycles. The primary endpoint timeframe is stated as extending from the start of study-drug administration to the end of the study, up to 3.1 years. The registry does not report individual treatment durations or the actual number of visits.

TAK-771 includes Immune Globulin Infusion 10% and recombinant human hyaluronidase. The administration description specifies a subcutaneous infusion of the hyaluronidase solution, followed by the subcutaneous immune globulin infusion within 10 minutes of the first infusion's completion.

Because there is no concurrent control group, the design can describe events recorded during TAK-771 exposure but cannot establish a comparative treatment effect against an untreated or alternative-treatment group. The registry record does not report the protocol rationale, eligibility details beyond the stated population, or a statistical design justification.

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 who completed the study TAK-771-3004 (NCT05150340) were enrolled in this extension study and continued to receive TAK-771.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: EXSAS included all enrolled participants who received investigational drug in Study TAK-771-3005 at least once.

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: Safety Analysis Set for Extension Study (EXSAS) included all enrolled participants who received investigational drug in Study TAK-771-3005 at least once.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), measured over From start of study drug administration up to end of study (up to 3.1 years).

The primary endpoint is the percentage of participants with treatment-emergent adverse events (TEAEs), assessed from the start of study-drug administration through the end of the study, up to 3.1 years. The registry defines an adverse event broadly as an unfavorable or unintended medical occurrence during a clinical investigation, whether or not it is considered related to the investigational product. Events can include symptoms, diseases, or clinically significant laboratory findings.

A TEAE is an event that emerges or becomes apparent after treatment begins, or an existing event that worsens in intensity or frequency after exposure. This timing-based definition is used to organize safety observations during treatment; it does not, by itself, show that treatment caused an event. Causality is a separate judgment and the registry definition explicitly allows events to count whether or not a causal relationship is suspected.

Reporting the percentage of participants with at least one event gives a participant-level summary of how widespread the recorded events were. It does not describe the total number of episodes, their duration, severity, or clinical course. Those details require separate event-level reporting. The registry record does not state a numerical result for the primary endpoint or provide a confidence interval for that percentage.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant-level percentage describe?

In general, a participant-level event percentage counts participants who experienced at least one qualifying event and relates that count to the number of participants assessed. It differs from an event count: one participant may experience more than one event, while the participant-level measure counts that person once for the endpoint. It also differs from an exposure-adjusted rate, which accounts for the time participants were observed. The registry identifies the primary endpoint as a percentage of participants, but does not report its numerical estimate in the record.

The adverse-event summary lists 15 participants in the other adverse-event category and 6 in the serious adverse-event category, with 15 participants at risk for each category. Those category counts are descriptive. The record does not provide the event-level data needed to determine how many total episodes occurred, how events were distributed over time, or whether the same participants contributed to both categories.

Why does a single-group design matter?

In general, a control group helps distinguish changes associated with an intervention from background events, changes over time, and other influences. A single-group extension can document what occurred during treatment and can be useful for observing safety in the participants followed. It cannot, on its own, estimate a treatment-versus-control difference. Since this study is non-controlled and has no randomized allocation, comparisons with an outside population would require additional information and assumptions that the registry record does not report.

Open-label means masking was not used. In general, knowledge of treatment assignment can influence reporting, assessment, or clinical management, depending on the outcome and study procedures. The registry does not describe any procedures intended to reduce such influences, so none should be assumed.

How should uncertainty be understood?

In general, a confidence interval gives a range of values compatible with the data under a specified statistical method. It communicates estimation uncertainty and is not a guarantee that the true value lies in that range. For a participant-level percentage, uncertainty is important because a result from a limited enrolled group may be imprecise. The registry record does not report a confidence interval or other uncertainty measure for the primary endpoint.

In general, statistical significance tests address a specified hypothesis under a stated analysis plan. A p-value does not measure the probability that a treatment works, and it does not communicate the size or practical importance of an effect. No p-value or inferential result for the primary endpoint is reported in the registry record. The record also does not report a statistical analysis plan, model, or adjustment strategy.

What do planning calculations mean?

In general, sample-size calculations are planning illustrations: they describe the number of participants that might be needed under stated assumptions to detect a specified effect with a chosen error rate and power. They are not results from the participants who took part, and they are never observed power. The registry record does not report a study-specific sample-size justification. Any planning illustration should therefore be read as conditional on its assumptions, not as evidence about what this extension demonstrated.

For planning, over-dispersion matters when observed variability is greater than a model assumes; ignoring it can make uncertainty appear too small. That concept is general. The primary endpoint is a participant-level binary outcome, and the registry does not report an over-dispersion assessment or an analysis model. No assumption about such an assessment can be made from the record.

In general, interpretation also depends on how the analysis population is defined, how missing outcomes are handled, and whether follow-up differs among participants. The registry describes the endpoint population as enrolled participants who received investigational drug at least once in Study TAK-771-3005. It does not state how missing endpoint data were handled or whether analyses used any other population definition.

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("TAK-771")
n      <- c(15)
events <- c(15)
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  TAK-771  15  15  100.0  78.2  100.0  79.6  100.0  79.4  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity strategy. Multiplicity arises in general when several outcomes, comparisons, or repeated tests are assessed, because the chance of a false-positive finding can increase across tests. The record lists two outcome measures and zero analyses, but gives no testing hierarchy, adjustment method, or planned inferential procedure. Without such details, no claim about control of multiplicity can be made.

Missing-data handling is also not reported in the registry record. The record does not state whether any endpoint observations were missing, how missing values were treated, or whether any sensitivity analyses were planned or performed. This matters in general because the observed percentage can depend on who has outcome information and how incomplete follow-up is handled. The posted counts alone do not establish that follow-up or endpoint assessment was complete for every participant.

The primary endpoint population is described as all enrolled participants who received investigational drug at least once in Study TAK-771-3005. The registry lists 15 enrolled participants, and the adverse-event categories each list 15 participants at risk. These statements describe the population and denominators reported for the safety summary; they do not provide detail on withdrawals, exposure duration, or missing endpoint information.

There is no reported statistical analysis plan, and no analysis results are listed. The registry record therefore does not establish whether any analyses beyond the descriptive adverse-event counts were conducted, how analysis populations were handled, or how multiple outcomes were prioritized.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: adrenal insufficiency (6.7%), covid-19 (6.7%), diarrhoea (6.7%), eyelid ptosis (6.7%), hypoglycaemia (6.7%).

The adverse-event summary lists 6 participants with serious adverse events among 15 at risk and 15 participants in the other adverse-event category among 15 at risk. These are participant counts, not counts of individual event episodes. The record does not provide event-level totals or clarify whether participants could appear in both categories.

The serious-event terms listed are Adrenal insufficiency, COVID-19, Diarrhoea, Eyelid ptosis, Hypoglycaemia, and Inflammatory bowel disease. Each is reported at 6.7%. The registry does not give a separate participant count for each term or explain overlap between terms, so those percentages should not be summed or treated as mutually exclusive groups. The terms identify reported events; they do not by themselves establish that TAK-771 caused them.

In general, serious adverse events are a safety category distinct from all adverse events, and a participant may have serious or non-serious events. The registry summary does not provide the seriousness criteria applied to individual cases, event onset and duration, outcomes, or causality assessments. It also does not report exposure-adjusted rates. The counts should therefore be read as descriptive observations from this study, not as comparative risk estimates.

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

The registry record describes a completed, open-label extension study focused on long-term safety of TAK-771 in Japanese participants with primary immunodeficiency disease. It records adverse events during treatment and lists serious adverse-event terms. These observations add descriptive information about events recorded in the enrolled group during the study's follow-up period.

The record does not establish that TAK-771 caused any particular event. Its adverse-event definition includes events whether or not a causal relationship is suspected. The listed serious-event terms and participant counts therefore should not be read as causal conclusions. The record also does not compare participants receiving TAK-771 with a concurrent control group, so it cannot show whether event occurrence was higher or lower than under another treatment or no treatment.

The primary endpoint is intended to summarize the percentage of participants with TEAEs, but its numerical result and uncertainty are not reported in the registry record. The safety counts cannot replace a complete endpoint analysis. They also do not reveal the number of event episodes, the timing or duration of events, or whether each participant had comparable exposure and follow-up.

In general, a descriptive result can identify what was recorded in a study group while leaving uncertainty about comparative effects and causal attribution. Interpretation of long-term safety also depends on follow-up completeness, event ascertainment, and exposure time. These details are not reported in the registry record. The appropriate reading is therefore limited to the posted descriptive counts and event terms, without inferring efficacy, comparative safety, or an unreported statistical conclusion.

14. Why This Trial Matters Statistically

Long-term safety is an important statistical question because some events may be observed only with continued follow-up. An extension study can add observations beyond an earlier study, and this record describes continued TAK-771 treatment after participation in TAK-771-3004 for eligible participants. Its stated focus is safety during longer-term exposure, with a primary endpoint spanning treatment initiation through the end of the study, up to 3.1 years.

Statistically, the single-group design makes clear what kind of evidence the record can offer: descriptive counts among participants receiving TAK-771. It does not support a randomized comparison or a direct estimate of how outcomes differ under another treatment. Keeping that distinction explicit helps readers avoid treating event frequencies as treatment effects.

The record also illustrates why a percentage alone is not a complete account of safety. The number of participants with events, the time they were observed, the number and nature of event episodes, and uncertainty around estimates all matter. Here, the registry provides participant counts and a list of serious-event terms, but it does not report a numerical primary endpoint estimate, uncertainty interval, or exposure-adjusted rate.

These limits do not erase the value of the observations. They define their scope. The posted information can document events recorded in this extension group and can inform what further detail is needed for a fuller statistical assessment. It cannot answer comparative or causal questions that the study design and registry reporting do not address.

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 principal limitation for interpretation is the absence of a concurrent control group. The study is single-group and non-controlled, so the adverse-event counts cannot estimate a contrast with another treatment or with no treatment. Open-label conduct also means masking was not used; the registry record does not describe how event assessment or reporting may have been standardized.

The registry does not report the numerical result for the primary endpoint, a confidence interval, a p-value, or an analysis method. It lists zero analyses. As a result, the precision of the primary TEAE percentage cannot be evaluated from the record, and no inferential conclusion should be attributed to the study.

Follow-up and exposure details are limited. The intended treatment period is described as 3 years, while the primary endpoint timeframe is stated as up to 3.1 years. The record does not provide individual exposure or follow-up durations, withdrawals, completion information, event timing, or exposure-adjusted rates. It also does not report missing-data procedures or whether any endpoint data were missing.

The serious adverse-event terms are reported at 6.7% each, without term-specific participant counts or information about overlap among terms. The registry does not provide case-level descriptions, seriousness assessments, outcomes, or causal evaluations. Finally, the study population is described as Japanese participants with PID, but additional characteristics relevant to judging applicability are not reported in this record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Long-term Safety of TAK-771 in Japanese Primary Immunodeficiency Disease (PID) Participants — NCT05513586.
• Registry record last updated 2026-05-19; status last verified 2026-05.
• Results first posted 2026-05-19.
• 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

This is a completed Phase 3, open-label, non-controlled, single-group extension study of TAK-771 in Japanese participants with primary immunodeficiency disease. The registry lists 15 enrolled participants. Treatment combines Immune Globulin Infusion 10% and recombinant human hyaluronidase, administered by subcutaneous infusion.

The primary endpoint is the percentage of participants with treatment-emergent adverse events from treatment initiation to study end, up to 3.1 years. The adverse-event summary lists 15 participants in the other adverse-event category and 6 with serious adverse events, each among 15 at risk. Six serious-event terms are listed at 6.7% each. A numerical primary endpoint estimate, uncertainty interval, statistical analysis plan, and missing-data approach are not reported in the registry record.