A Study of TAK-662 for Japanese Patients With Congenital Protein C Deficiency: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of TAK-662 for Japanese Patients With Congenital Protein C Deficiency (NCT04984889), a na phase 1, phase 2 study. The primary outcome is PK Part: Protein C Activity Level of TAK-662.

2. Clinical Question

3. Trial Design

This completed Phase 1/2 study evaluated TAK-662 in Japanese participants with congenital protein C deficiency. It was open-label, with no masking, and used a single-group design. The registry record lists enrollment of 5 and identifies Takeda as the sponsor. The study started on 2021-09-07, reached primary completion on 2022-03-29, and is listed as completed.

The pharmacokinetic part focused on protein C activity after a single intravenous infusion of TAK-662 80 IU/kg over 15 minutes on Day 1. Blood collection was scheduled before infusion and at 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion. The brief description states that participants stayed at the clinic until 3 days after infusion and returned 7 days after infusion for side-effect checks.

Participants completing the pharmacokinetic part could continue into an extension part. The extension offered on-demand treatment, short-term prophylaxis, or long-term prophylaxis until commercial protein C concentrate was available at each study site or the study ended. The registry record gives adverse-event summaries separately for these extension approaches. They should not be treated as randomized groups: allocation is listed as not applicable, and there is no stated control arm. How participants were assigned among extension approaches is not reported in the registry record.

The design can describe pharmacokinetic measurements and recorded safety experiences in this study cohort. It cannot by itself estimate a controlled treatment contrast. The protocol details beyond the registry description, including the sample-size justification and any interim analyses, are not reported in the registry record.

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: A total of 5 Japanese participants were enrolled in this 2-part study to receive TAK-662 in Pharmacokinetic (PK) part (Part 1) followed by 3 treatment options in the Extension part (Part 2) (on-demand, short-term, or long-term prophylaxis). As per planned analysis, the Extension Part data was collected, analyzed and reported as per On-demand and Short-term Prophylaxis treatments and per dose level wise data was not collected in this study.

PK Part: Up to 7 Days

Extension Part: Up to 35 Months

Analysis population for the primary outcome, as defined in the registry: The PK population included all study participants who took at least 1 dose of TAK-662 and had enough number of quantifiable blood levels for TAK-662 collected post-dose without important protocol deviations (PDs)/violations or events thought to substantially affect the PK.

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: The safety population included all enrolled participants in the study who took at least 1 dose of TAK-662.

6. Primary Endpoint

The registry lists the primary outcome as PK Part: Protein C Activity Level of TAK-662, measured over Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion.

The primary endpoint is protein C activity level of TAK-662 in the pharmacokinetic part. Protein C activity was measured with chromogenic assays, and the registry describes the summary measure as a mean with standard deviation. Measurements were scheduled before infusion and at 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion. The unit is international unit per milliliter (IU/ml).

These measurements are intended to characterize the amount of functional protein C activity detected in blood over time after infusion. In general, repeated measurements after dosing can help describe a concentration or activity-time profile; they are not, on their own, a comparison of treatment effects against a control group. The study summary says the pharmacokinetic information was intended to support dose selection for future use.

The registry record identifies the endpoint, assay, summary measure, and collection schedule, but does not report numerical values for protein C activity at any time point. It also does not report confidence intervals or a statistical comparison for this endpoint. Consequently, the magnitude and precision of the activity measurements cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a mean and standard deviation for a continuous pharmacokinetic endpoint. The study is single-group and open-label; the primary endpoint is a sequence of measurements after a single infusion, rather than a randomized comparison between treatment arms. The registry record does not report an inferential analysis for the primary endpoint, numerical endpoint estimates, or confidence intervals.

What does a mean describe?

In general, a mean is a measure of the central level of a set of observations. For this study, it would summarize protein C activity measurements at a particular collection time among participants included in the analysis. A mean is useful for describing the typical level in the observed data, but it can be affected by unusually high or low observations. With a small cohort, each participant’s measurements can have substantial influence on the summary.

What does a standard deviation describe?

In general, a standard deviation describes how dispersed observations are around their mean. It is a measure of variation among the observed values, not a measure of uncertainty in the estimated mean. A small standard deviation would indicate measurements clustered relatively close to the mean; a larger one would indicate greater spread. The endpoint’s standard deviations are not reported in the registry record, so observed variability cannot be assessed.

How should repeated measurements be understood?

Measurements were scheduled before infusion and at 0.5, 1, 2, 4, 8, 12, 24, and 36 hours after infusion. In general, repeated measurements from the same participant are related rather than independent. A complete analysis could account for that within-participant relationship when estimating change over time or modeling an activity-time profile. The registry record does not report whether such a model was used, whether the endpoint was analyzed only descriptively, or how incomplete measurement series were handled.

The listed mean and standard deviation are straightforward descriptive summaries at each time point. They do not, by themselves, test whether activity changed from pre-infusion levels or estimate a treatment effect against a comparator. A confidence interval, in general, conveys uncertainty around an estimated quantity under the assumptions of the analysis. No confidence interval for the primary endpoint is reported in the registry record.

What can the design establish?

A single-group study can describe observations among participants who received TAK-662, but without a control group it cannot separate treatment-related change from other explanations for change over time. Open-label status means masking is not reported; expectations or knowledge of treatment could also affect some assessments, particularly subjective outcomes. The primary endpoint is based on laboratory assays, but assay procedures beyond the chromogenic method are not reported in the registry record.

The adverse-event summaries are also descriptive. Counts of participants with events can communicate what was recorded in this cohort, but they do not provide a controlled estimate of excess risk. Exposure differs by study part and extension approach, and detailed exposure duration and event timing are not reported. The counts should not be treated as directly comparable rates across groups.

The registry record states that no analysis entries are listed. It notes planning-illustration assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation, with a target effect expressed as a fraction of an observed effect. Those assumptions describe a planning illustration rather than an analysis of this single-group study. Planning sample sizes are not observed power, and the sample-size justification for the trial is not reported in the registry record. No calculated planning sample-size values are reported in the registry record.

General statistical point: estimates from small studies are typically uncertain, and a lack of a reported significant test would not prove the absence of an effect. Here, the registry record does not supply primary endpoint estimates or test results, so neither effect magnitude nor statistical uncertainty can be evaluated. Any detailed model choice, adjustment strategy, or handling of outliers is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint involves activity measurements at multiple scheduled times. The registry record does not report whether each time point was treated as a separate endpoint, whether a repeated-measures model was used, or whether any adjustment was made for multiple comparisons. It also does not report a prespecified hierarchy of primary and secondary tests. A multiplicity strategy is therefore not reported in the registry record.

The record lists 12 outcome measures and describes secondary safety and extension outcomes, including event counts and episode-based outcomes. The outcome descriptions do not include numerical results for the extension measures. Whether all listed outcomes were analyzed, and how multiple outcome tests were handled, is not reported in the registry record. Without a stated analysis plan and results, it is not possible to assess selective emphasis among outcomes.

The pharmacokinetic population is described as participants who took at least 1 dose of TAK-662, had enough quantifiable post-dose blood levels, and had no important protocol deviations, violations, or events thought to substantially affect pharmacokinetics. The number included in that population is not reported in the registry record. The record does not give a separate description of the population used for each safety or extension outcome.

Missing measurement counts, reasons for missingness, imputation methods, and sensitivity analyses are not reported in the registry record. It is also not reported how below-quantification measurements, protocol deviations, or incomplete follow-up were handled in the analysis. These details matter because available-case summaries may describe a different set of observations at different time points. The registry record does not permit assessment of whether missing data could have influenced the endpoint summaries.

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

For the pharmacokinetic part, the registry lists 5 participants at risk for serious adverse experiences and 0 with serious adverse experiences; it lists 5 at risk for other adverse experiences and 2 with other adverse experiences. No deaths are listed. For on-demand extension treatment, the corresponding counts are 4 at risk and 0 with serious adverse experiences, and 4 at risk and 3 with other adverse experiences; no deaths are listed.

For short-term prophylaxis, 1 participant is listed at risk, with 0 serious and 0 other adverse experiences and no deaths. For long-term prophylaxis, 0 participants are listed at risk, and the adverse-event counts and deaths are also listed as 0. With no participants at risk in that group, these entries do not provide evidence about safety during long-term prophylaxis.

The record lists no serious adverse-event terms. These counts are descriptive and should not be interpreted as estimates of comparative risk. The record does not report event timing, duration of exposure for each participant, severity details beyond the serious/other categories, or a comparison group. The counts also do not establish that no unrecorded or later events occurred.

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

The registry record shows that the study was designed to measure protein C activity after TAK-662 infusion and to collect safety information during the pharmacokinetic and extension parts. It also documents the intended extension treatment approaches and lists participant counts for adverse experiences. These details clarify what the study set out to observe, but they are not a substitute for outcome estimates.

Numerical values for the primary protein C activity endpoint are not reported in the registry record. Without those values, readers cannot determine the observed activity levels, the change over time, or the variability of measurements. The record also does not provide confidence intervals or an inferential analysis for the primary endpoint. Therefore, the statistical precision of the pharmacokinetic findings cannot be assessed.

The adverse-event counts show what was recorded in the listed study groups. They are not a comparison with an untreated group or another therapy, and the study design does not support causal comparisons among extension approaches. Small group sizes and the absence of a control group limit how broadly these observations can be interpreted. The extension efficacy outcome results are not reported in the registry record.

The study summary says the pharmacokinetic information was intended to help the sponsor work out a dose for future use. The registry information available does not establish a preferred dose, quantify clinical benefit, or determine comparative safety. Those conclusions would require results and analyses that are not reported in the registry record. Statistical interpretation should remain at the level of the described design and the counts and endpoint definitions that are actually recorded.

13. Why This Trial Matters Statistically

This trial is statistically notable as a small, single-group pharmacokinetic study in a specific population: Japanese participants with congenital protein C deficiency. Its design is suited to collecting post-infusion activity measurements and documenting safety experiences in the enrolled cohort. The scheduled measurements span pre-infusion through 36 hours post-infusion, giving the study a repeated-measurement structure.

That structure raises general analytic considerations. Measurements from the same participant are related, and missing measurements at some collection times can affect the pattern of available observations. Descriptive means and standard deviations can convey central tendency and variability, but uncertainty around estimates and the approach to repeated measurements are important for interpretation. Those numerical estimates and analysis details are not reported in the registry record.

The small enrollment and lack of a comparator also shape the inference. The record can describe observations among participants who received TAK-662, but it cannot establish how those observations differ from an alternative treatment or from what would have occurred without treatment. Extension treatment options add clinically relevant follow-up questions, while the registry's lack of numerical extension outcome results prevents statistical assessment of those questions.

Finally, the record illustrates why endpoint definitions and outcome data must be read separately. A clearly described endpoint and collection schedule do not reveal the observed result when estimates are absent. The adverse-event counts provide limited descriptive information, but they do not replace a comparative safety analysis. The study's statistical contribution cannot be judged fully from the available registry entries without primary endpoint values, uncertainty estimates, and fuller analysis details.

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 the primary objective is that numerical protein C activity results are not reported in the registry record. Although the endpoint, assay type, summary measure, and collection times are specified, no means, standard deviations, or confidence intervals are listed. The magnitude and precision of the pharmacokinetic profile therefore cannot be evaluated.

Enrollment was 5, and the study had no control group. This limits both the stability of descriptive summaries and the ability to attribute observed changes to TAK-662 rather than other influences. The number included in the pharmacokinetic population is not reported in the registry record, so it is not possible to establish how many contributed to the primary endpoint.

The extension part involved different treatment approaches, but assignment procedures, exposure duration, and participant-level outcome details are not reported in the registry record. The extension outcome results are also not reported. The groups should not be treated as comparative arms, and the record does not support comparative estimates across those approaches.

Important analysis details are absent, including handling of missing measurements, the statistical model for repeated observations, multiplicity procedures, and sensitivity analyses. The sample-size justification and interim analysis plans are not reported in the registry record. Adverse-event reporting is limited to summary counts; event timing and detailed exposure information are not reported. These limitations constrain assessment of both precision and generalizability.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of TAK-662 for Japanese Patients With Congenital Protein C Deficiency — NCT04984889.
• Registry record last updated 2025-05-07; status last verified 2025-04.
• Results first posted 2024-01-05.
• 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

NCT04984889 is a completed, open-label, single-group Phase 1/2 study sponsored by Takeda. It enrolled 5 Japanese participants with congenital protein C deficiency. The pharmacokinetic part assessed protein C activity after a single intravenous TAK-662 infusion, with measurements scheduled before infusion and through 36 hours post-infusion. Participants completing that part could enter an extension offering on-demand treatment, short-term prophylaxis, or long-term prophylaxis.

The registry record identifies the primary endpoint as mean protein C activity with standard deviation, but does not report numerical primary endpoint results. It lists adverse-event counts by study part and extension approach, including no serious adverse experiences in groups with participants listed at risk. The single-group design, small enrollment, absent comparator, and missing endpoint estimates limit statistical interpretation. Extension outcome results and key analysis details are not reported in the registry record.