Safety and Efficacy of Turoctocog Alfa in Previously Treated Male Children With Haemophilia A: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Turoctocog Alfa in Previously Treated Male Children With Haemophilia A (NCT01138501), a non-randomized phase 3 study. The primary outcome is The Incidence Rate of FVIII Inhibitors (Greater Than or Equal to 0.6 Bethesda Units (BU)).

2. Clinical Question

The study was designed to investigate safety and efficacy among previously treated male children with haemophilia A. Its primary endpoint focuses on inhibitors, an outcome defined by a laboratory threshold. The endpoint’s stated denominator is based on exposure days and includes participants with inhibitors even if they had fewer than 50 exposure days. That rule matters when interpreting which participants contribute to the endpoint.

The registry record describes a safety analysis set of 63 treated subjects and says the primary analysis included all subjects with at least 50 exposure days and/or with inhibitors. It also reports that 59 subjects had at least 50 exposure days. Those population details do not reveal how many participants met the inhibitor threshold. The number with inhibitors, the resulting incidence estimate, and its uncertainty are not reported in the registry record.

3. Trial Design

This was a phase 3, multicentre, open-label, non-controlled trial. It used a single-group, non-randomized design. The registry record describes the trial as taking place in Asia, Europe, and North and South America. The recorded enrollment was 65, and the status is completed. The recorded start is 2010-06, with primary completion in 2011-11.

Participants received turoctocog alfa. Because there was no control group and no random allocation, the trial is not a randomized comparison of treatments. The registry record’s intervention listing contains turoctocog alfa twice, but that listing does not establish two distinct treatment groups; the described trial model is single-group, and the arm description identifies rFVIII. The registry record does not report a separate comparator.

Open-label means treatment assignment was not masked from participants or investigators. In a single-group study, outcomes are observed among treated participants rather than contrasted against a concurrent control group. This can describe what was recorded during treatment, but it does not by itself distinguish treatment effects from other influences, such as the underlying condition, prior treatment history, or how outcomes are assessed. These are general design considerations, not additional findings about this trial.

The safety analysis set comprised 63 subjects who received at least one dose. The primary endpoint used a more specific analysis population: subjects with at least 50 exposure days and/or with inhibitors. The record says 59 subjects had at least 50 exposure days. Enrollment, treated population, and endpoint population therefore refer to different stated groups; the registry record does not explain the status of every enrolled subject in further detail.

Further protocol detail, including the planned sample-size justification, is not reported in the registry record. A planning illustration based on an observed effect is not the trial’s design justification, and its assumptions describe an imagined two-arm calculation rather than the single-group structure used in this trial.

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 safety analysis set includes all 63 subjects who received at least one dose of the investigational product. The analysis of the primary endpoint included all subjects with at least 50 exposure days and/or with inhibitors. A total of 59 subjects had 50 exposure days (EDs).

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 The Incidence Rate of FVIII Inhibitors (Greater Than or Equal to 0.6 Bethesda Units (BU)), measured over The adverse events were collected throughout the trial, corresponding to an average of 138 days per subject..

The primary endpoint is the incidence rate of factor VIII inhibitors at a threshold of at least 0.6 Bethesda Units (BU). Its stated unit is the number with inhibitors divided by the number with at least 50 exposure days, with an explicit inclusion rule: participants with inhibitors are included in the denominator even if they had fewer than 50 exposure days. The primary analysis population therefore includes all subjects who met either condition.

Inhibitors are antibodies that interfere with factor VIII activity. General explanation: a laboratory threshold gives a consistent rule for classifying whether a measured inhibitor level counts toward an endpoint. Reporting the number meeting that threshold can describe how often the event was observed in the defined population. It does not, on its own, establish why the event occurred.

The endpoint is relevant to a safety and efficacy study of factor VIII because inhibitor development can affect the response to replacement factor. The registry record states that adverse events were collected throughout the trial, corresponding to an average of 138 days per subject. It does not provide the number of participants with inhibitors, the calculated endpoint value, or an uncertainty interval. The endpoint’s name and calculation definition should therefore not be mistaken for a reported outcome result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: The methods below explain how to interpret the design and endpoint definitions in the registry record. They do not fill in results that the record does not report.

What does the inhibitor endpoint count?

The primary outcome is described as an incidence rate, but its stated unit is a count of participants with inhibitors divided by a defined participant denominator. The denominator includes subjects with at least 50 exposure days and any subjects with inhibitors who had fewer than 50 exposure days. This is a specific endpoint rule: it avoids excluding an inhibitor case solely because the participant had fewer exposure days than the usual threshold.

General explanation: exposure days provide a measure of how often participants received the factor product. A minimum exposure requirement can make comparisons of inhibitor occurrence more interpretable when participants have had different opportunities for exposure. However, the inclusion rule and denominator need to be read together. A participant can qualify through the exposure-day criterion or through having inhibitors. The registry record does not provide enough counts to rebuild the endpoint denominator or calculate the endpoint independently.

What does a confidence interval tell a reader?

General explanation: a confidence interval expresses the statistical uncertainty around an estimated quantity under a specified analysis. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. It is not a guarantee that the true value lies within the interval, nor does it address biases from study design or outcome measurement.

The registry record does not report a confidence interval for the primary endpoint. It also does not report the inhibitor count or the endpoint estimate. Consequently, the precision of the primary result cannot be assessed from the record. No uncertainty range should be inferred from the sample sizes alone.

Why does the single-group design matter?

General explanation: random allocation to concurrent groups is one way to balance known and unknown characteristics, on average, and to support a treatment comparison. This trial was non-randomized and single-group, with no control group. Its results can describe outcomes recorded among treated participants, but the design does not offer a concurrent estimate of what would have happened under an alternative treatment or without the study treatment.

Open-label conduct means that treatment was not masked. In general, knowledge of treatment can influence some aspects of outcome assessment or reporting, especially when an outcome involves judgment. A laboratory-defined inhibitor threshold may be more objective than a subjective outcome, but the registry record does not describe laboratory procedures, assessor masking, or other measures used to reduce assessment bias. Those details are not reported in the registry record.

How should the analysis population be read?

The record distinguishes enrollment from the safety and primary endpoint populations. Enrollment was 65. The safety analysis set consisted of 63 subjects who received at least one dose. The primary endpoint analysis included all subjects with at least 50 exposure days and/or inhibitors; 59 subjects had at least 50 exposure days. These descriptions should not be collapsed into a single denominator. The number of participants in the endpoint analysis is not stated as a standalone total, and the record does not provide a participant flow explaining every difference.

General explanation: analysis populations define which observations contribute to a result. A broader safety population can include treated participants regardless of whether they meet an endpoint-specific exposure rule. A primary outcome population can use additional eligibility criteria. If exclusions or missing measurements occur, their number and reasons can affect interpretation; such details are not reported in the registry record.

What can planning calculations establish?

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. This is a planning framework, not a description of the single-group trial’s actual design. The sample-size assumptions do not show that the trial was powered for a particular endpoint, and a planning sample size is not observed power.

General explanation: power is a design-stage probability of detecting a specified effect under specified assumptions. It is not the probability that a treatment works, and it does not describe the probability that an observed result is true. Any planning illustration based on an observed effect is conditional on that effect and on the calculation assumptions. The trial’s own sample-size justification is not reported in the registry record.

The record does not report an analysis plan, inferential test for the primary endpoint, confidence intervals, interim analyses, or a multiplicity procedure. The absence of those details limits assessment of how analyses were planned and whether results were adjusted for multiple outcome testing. It does not establish that a particular method was or was not used outside what is recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists the incidence of factor VIII inhibitors as the primary outcome and frequency of adverse events as a secondary outcome. It reports two outcome measures and zero analyses. The specific statistical plan, including whether any multiplicity adjustment was planned, is not reported in the registry record.

General explanation: multiplicity arises when several outcomes, comparisons, time points, or statistical tests are considered. Without an analysis plan, a reader cannot determine how the investigators intended to distinguish primary from exploratory findings or whether the chance of false-positive findings across multiple tests was addressed. The record’s identification of primary and secondary outcomes helps describe their stated roles, but it does not provide a complete analysis strategy.

Missing-data methods and the amount or pattern of missing outcome data are not reported in the registry record. The record states that the safety set includes all 63 subjects who received at least one dose and that the primary endpoint analysis includes all subjects with at least 50 exposure days and/or with inhibitors. It also states that 59 subjects had at least 50 exposure days. These inclusion details are not a substitute for a missing-data account; they do not show whether endpoint measurements were unavailable or how any unavailable measurements were handled.

The primary endpoint result itself is not reported in the registry record. No inhibitor count, endpoint estimate, confidence interval, or inferential result is available in the recorded information. Accordingly, multiplicity, missing-data handling, and precision cannot be evaluated from reported endpoint analyses. No conclusion about the appropriateness of unreported methods should be inferred from that absence.

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: device related infection (1.6%), gastroenteritis viral (1.6%), soft tissue injury (1.6%).

The safety results identify 63 treated subjects as the group at risk. Among them, 3 had serious adverse events, and 14 had other adverse events. These are participant counts in the posted results, not counts of all event episodes. The registry record does not provide a death count; deaths are not reported in the registry record.

The listed serious adverse event terms are device related infection, viral gastroenteritis, and soft tissue injury, each reported as 1.6%. These terms describe events recorded in the trial. The percentages do not establish whether an event was caused by turoctocog alfa, and the record does not provide event narratives or an assessment of causality. The three terms should not be treated as an exhaustive account of every serious event unless the registry record says so; it does not clarify that point.

General explanation: safety counts are most useful when read with their population, time period, and event definitions. The record describes adverse events as collected throughout the trial, corresponding to an average of 138 days per subject. That summary does not mean every participant had the same follow-up duration. The record does not report additional detail on individual follow-up, event recurrence, severity beyond the serious-event classification, or the method used to judge relatedness.

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

The registry record describes a completed phase 3 study of turoctocog alfa in previously treated male children with haemophilia A. It documents a single-group, non-randomized, open-label design and identifies the primary endpoint as the incidence of factor VIII inhibitors at a threshold of at least 0.6 Bethesda Units (BU). It also gives the endpoint population rule and the treated safety population.

What the record does not provide is the primary inhibitor outcome: the number of participants with inhibitors, the endpoint estimate, and its statistical uncertainty are not reported in the registry record. Therefore, the stated endpoint cannot be used to quantify inhibitor occurrence from this record alone. The outcome definition is not itself a result.

The posted safety counts describe adverse events observed among treated participants: 3 participants had serious adverse events, and 14 had other adverse events, among 63 treated subjects. Three serious-event terms are each listed at 1.6%. These observations are descriptive. They do not establish that the intervention caused the events, and the record does not report a death count.

The design also limits what can be concluded comparatively. With no concurrent control group and no random allocation, the study does not directly estimate how outcomes would differ under another treatment or no treatment. General explanation: causal interpretation requires attention to alternative explanations, measurement, and the study design; a single-group observation cannot resolve those issues by itself.

These limitations do not negate the descriptive value of the recorded study. They define what can and cannot be learned from the available registry information. Protocol details, the statistical analysis plan, missing-data methods, interim analyses, and sample-size justification are not reported in the registry record. No treatment recommendation or claim of efficacy can be drawn from the recorded information alone.

13. Why This Trial Matters Statistically

This trial is statistically informative in part because it makes the endpoint population rule explicit. The primary analysis included subjects with at least 50 exposure days and/or with inhibitors, and participants with inhibitors but fewer exposure days were included under the stated definition. Such rules affect the denominator and should be considered alongside the endpoint label. The record also reports that 59 subjects had at least 50 exposure days.

The study illustrates the distinction between enrollment and analysis populations. Enrollment was 65, the treated safety population was 63, and the primary endpoint population followed its own inclusion rule. Keeping these populations distinct prevents an incorrect assumption that every reported measure uses the same denominator.

It also demonstrates why design and outcome reporting must be considered together. The study was open-label, non-randomized, and single-group, so its data are descriptive rather than a randomized treatment comparison. The record includes safety counts but does not report the primary inhibitor result. Clear outcome definitions cannot compensate for missing outcome estimates; readers need both the rule for measuring an endpoint and the result obtained under that rule.

General statistical explanation: a study’s usefulness depends not only on its sample size or phase designation, but also on how participants are selected, how outcomes are defined, and how uncertainty and missing data are reported. In this case, the registry record helps readers identify the intended endpoint and treated population, while leaving the primary endpoint result and several analysis details unavailable. Recognizing both what is documented and what is not is essential to avoid overinterpreting a study record.

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 primary endpoint result is not reported in the registry record. The number of subjects meeting the inhibitor threshold, the calculated endpoint estimate, and a confidence interval are also not reported. This prevents assessment of the observed frequency and its precision.

The single-group, non-randomized, open-label design provides no concurrent control comparison. It cannot by itself separate outcomes associated with treatment from other influences. The registry record does not describe specific masking or outcome-assessment safeguards beyond stating that the trial was open-label.

The analysis population is described by criteria, but the total number meeting the primary endpoint inclusion rule is not stated as a separate count. The record says 59 subjects had at least 50 exposure days and that participants with inhibitors were included even if they had fewer than 50 exposure days. The number of such participants, if any, is not reported in the registry record. Missing-data amounts, reasons, and handling methods are also not reported.

Further limitations include the absence of a reported statistical analysis plan, multiplicity approach, interim analysis details, and sample-size justification. The registry record lists safety counts and selected serious-event terms, but does not report a death count or further event-level details such as recurrence or causal assessment. These limitations concern the information available in the registry record; they do not establish what may have been collected elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy of Turoctocog Alfa in Previously Treated Male Children With Haemophilia A — NCT01138501.
• Registry record last updated 2017-03-17; status last verified 2017-02.
• Results first posted 2014-06-11.
• 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

The registry record describes NCT01138501 as a completed phase 3, multicentre, open-label, non-randomized, single-group trial of turoctocog alfa in previously treated male children with haemophilia A. Recorded enrollment was 65. The safety analysis set included 63 treated subjects; 59 had at least 50 exposure days.

The primary endpoint concerned factor VIII inhibitors at a threshold of at least 0.6 Bethesda Units (BU), using a denominator that included subjects with at least 50 exposure days and subjects with inhibitors even if they had fewer exposure days. The primary endpoint result is not reported in the registry record. Safety results state that 3 participants had serious adverse events and 14 had other adverse events among 63 treated subjects. A death count is not reported in the registry record.

The record does not report the statistical analysis plan, missing-data methods, multiplicity approach, or sample-size justification. The single-group design provides descriptive observations, not a randomized comparison.