Safety, Efficacy and Pharmacokinetics of NNC-0156-0000-0009 in Previously Treated Children With Haemophilia B.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Efficacy and Pharmacokinetics of NNC-0156-0000-0009 in Previously Treated Children With Haemophilia B. (NCT01467427), a na phase 3 study. The primary outcome is Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU).

2. Clinical Question

The trial’s broader stated aim was to evaluate safety, efficacy and pharmacokinetics, meaning exposure of the trial drug in the body. The registry lists secondary outcomes concerning bleeding episodes during prophylaxis, haemostatic response to treatment of bleeding episodes, factor IX recovery and levels, terminal half-life, and adverse events. These listed outcomes describe the topics the trial assessed; they do not establish what the findings were. Their results are not reported in the registry record.

The central statistical question is descriptive: what count of exposed participants met the prespecified antibody threshold during the stated observation period? With no comparator group, the primary endpoint cannot by itself provide a randomized estimate of a difference between treatments. The registry record also does not report the endpoint count or further detail about the timing or persistence of any antibody findings.

3. Trial Design

The registry identifies NCT01467427 as a Phase 3, completed, single-group study. Its title describes safety, efficacy and pharmacokinetics of NNC-0156-0000-0009 in previously treated children with haemophilia B. The intervention is listed as nonacog beta pegol. The registry reports an enrollment of 25, a start date of 2012-05-16 and a primary completion date of 2023-11-17.

The design information does not describe a concurrent control arm: allocation is listed as not applicable, masking as none, and the model as single-group. As a result, the design supports describing what was observed among participants exposed to the intervention, but it does not create a randomized comparison with an untreated or alternative-treatment group. Changes over time or observed events cannot be separated from other possible influences using a treatment contrast that the record does not describe.

The primary endpoint is the incidence of inhibitory antibodies against factor IX, defined as a titre above or equal to 0.6 Bethesda Units, from week 0 to week 52. The record says the analysis population includes all participants exposed to nonacog beta pegol. It also describes testing with either the Nijmegen modified factor IX Bethesda assay or a heat/cold Nijmegen modified factor IX Bethesda assay.

The registry lists several additional outcome topics, including bleeding during prophylaxis, haemostatic response, pharmacokinetic measures and adverse events. It lists 29 outcome measures, but no statistical analyses are listed in the registry record. The protocol, statistical analysis plan, specific analysis methods, interim analyses and sample-size justification are not reported in the registry record. Consequently, the registry information does not establish how every listed measure was analysed or how missing outcome data were handled.

There is a numerical inconsistency in the record: enrollment is listed as 25, while the serious-adverse-event age-group denominators are reported as 12, 23, 14 and 6. The record does not explain this difference. These values should therefore be read as the figures recorded for their respective contexts, not combined into an inferred overall study population.

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: The trial was divided into a 52-week main phase where patients received prophylaxis treatment until 50 EDs (Exposure days), followed by an extension phase.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analysis set (SAS) included all participants exposed to nonacog beta pegol.

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 Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU), measured over From week 0 to week 52.

The primary endpoint counts participants who developed inhibitory antibodies against coagulation factor IX (FIX). The registry defines a positive result as a titre above or equal to 0.6 Bethesda Units (BU), and gives the observation period as week 0 to week 52. It says the assay was either the Nijmegen modified factor IX Bethesda assay or a heat/cold Nijmegen modified factor IX Bethesda assay. The endpoint is reported in participants, rather than as a continuous laboratory measurement.

In general, an endpoint definition specifies which observations count as events, making the target of a reported count clearer. A threshold-based definition turns assay findings into an event classification according to the stated cutoff. The count can indicate how many participants met that definition in the analysis population, but it does not by itself describe the magnitude of titres, when a finding occurred, or whether it persisted. Those details are not reported in the registry record.

The Safety analysis set is defined as all participants exposed to nonacog beta pegol. That population definition identifies who was intended to contribute to the endpoint, but the registry does not report the number assessed for this endpoint or the number meeting its definition. The primary endpoint result is therefore not reported in the registry record.

This endpoint addresses an antibody-related safety question, while the trial’s broader aims also include efficacy and pharmacokinetics. It is not a direct measure of bleeding control or drug exposure. Those topics appear separately among the listed secondary outcomes, whose results are also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry is limited. It identifies the trial as single-group, gives the primary endpoint definition and population, lists outcome topics, and includes a description of a planning illustration. It does not report the study’s statistical analysis plan or the methods used to analyse the primary endpoint. The concepts below are general explanations, not claims about methods used in this trial unless explicitly identified as registry information.

What does a count endpoint represent?

The primary measure is a count of participants meeting an event definition. Here, the event is development of inhibitory antibodies against FIX at a titre above or equal to 0.6 BU during week 0 to week 52. In general, a count is easiest to interpret alongside its denominator: the count indicates how many people met the definition, while the denominator indicates how many people were assessed in the relevant population. A proportion can also describe the count relative to that denominator, but the registry does not report the primary endpoint count or denominator. No frequency can be inferred from the endpoint definition alone.

The record identifies the Safety analysis set as all participants exposed to nonacog beta pegol. That is the stated target population for the primary endpoint. The record does not report whether all exposed participants had an evaluable assay result throughout the specified period, how incomplete follow-up was treated, or whether any participants were excluded from the endpoint analysis.

Why does the threshold matter?

In general, a threshold transforms a laboratory measurement into a categorical event: results meeting the definition count as events, and results not meeting it do not. The registry’s stated cutoff is above or equal to 0.6 BU. Assay method and threshold are part of the endpoint definition because they determine how an event is classified. The registry names two assay approaches but does not report assay-level results, the number of tests, or how findings from the two approaches were combined.

A binary event classification is useful for answering a specific safety question, but it compresses information. It does not show the full distribution of titres or distinguish a borderline finding from a much higher titre once both meet the event definition. In general, those details may be relevant to interpretation, but they are not available in the registry record.

What can a single-group design estimate?

In general, a single-group study can describe outcomes observed among people receiving an intervention. It cannot, on its own, estimate a randomized difference from a comparator. This matters because background risk, changes over time and other influences may affect outcomes. With allocation listed as not applicable and the model listed as single-group, the trial record does not identify a like-for-like control comparison for the primary endpoint.

A confidence interval is a general way to express sampling uncertainty around an estimate. A narrow interval indicates greater precision under the chosen method, while a wide interval indicates less precision. Its interpretation depends on the analysis assumptions and the data used. The registry does not report a confidence interval or the method used to calculate one for the primary endpoint, so no interval-based assessment can be made from the record.

What does over-dispersion mean in general?

For count outcomes, a statistical model may assume a particular degree of variability. Over-dispersion means the observed variability exceeds what that model assumes. In general, ignoring over-dispersion can make uncertainty appear smaller than it is. Whether over-dispersion is relevant depends on the outcome and analysis; the registry does not report an analysis of this kind or a model for the primary endpoint. The primary outcome is a participant count, and no model-based estimate is reported.

How should planning illustrations be read?

The registry describes a planning illustration based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It states that the effect to detect is the stated fraction of the observed effect. For time-to-event tables, the described quantity is the total number of events; for other illustrations, it is participants per arm. These are planning assumptions, not a description of the trial’s single-group design or its observed endpoint result.

In general, a sample-size calculation asks what study size might be needed to detect an assumed effect under chosen statistical assumptions. It is sensitive to the assumed effect and analysis choices. A planning illustration based on an observed effect should not be interpreted as observed power, nor as evidence that the original trial was designed around those assumptions. The trial’s own sample-size justification and design calculations are not reported in the registry record. No planning values need to be treated as findings from this trial.

What analyses are documented?

The record lists 29 outcome measures and no statistical analyses. This means the registry information does not document analysis methods for those outcomes. It does not establish whether analyses were performed elsewhere, whether models or adjustments were used, or how multiplicity was addressed. Those details are not reported in the registry record. The endpoint definition and descriptive safety counts should not be mistaken for a complete statistical analysis plan.

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("Younger Children (0-6 Years)", "Older Children (7-12 Years)")
n      <- c(12, 13)
events <- c(0, 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  Younger Children (0-6 Years)  12  0  0.0  0.0  26.5  0.0  24.2  0.2  24.7
ARM  Older Children (7-12 Years)  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 29 outcome measures, including the primary antibody endpoint and secondary measures of bleeding, haemostatic response, pharmacokinetics and adverse events. When a study evaluates multiple outcomes, general statistical practice considers multiplicity: repeated testing can increase the chance of at least one apparently noteworthy finding when all tests are treated as independent opportunities for a positive result. Methods such as prespecifying a primary outcome or adjusting interpretation can address this issue, but the registry record does not report a multiplicity strategy or the statistical analysis plan. No claim can be made about whether or how multiplicity was handled.

The record defines the primary population as the Safety analysis set, including all participants exposed to nonacog beta pegol. It does not describe how missing assay results, incomplete follow-up, withdrawals, or other missing outcome data were handled. It also does not report how many participants contributed an evaluable primary endpoint result. These details are not reported in the registry record, so the effect of missingness on the endpoint cannot be assessed.

The primary endpoint result itself is not reported. The registry also does not list statistical analyses, so it does not establish whether the result was analysed using a particular model, whether any sensitivity analyses were conducted, or whether an analysis population beyond the stated Safety analysis set was used. Those elements should not be inferred from the outcome definition.

The age-group serious-adverse-event denominators are reported separately and do not match the stated enrollment of 25. The record does not explain the difference or describe whether these figures refer to a particular safety population or exposure period. That uncertainty limits interpretation of the safety counts. The registry record also does not report an explanation for missingness or a reconciliation of these population figures.

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: catheter site infection (8.3%), tourette's disorder (8.3%), viral upper respiratory tract infection (8.3%), haemoptysis (7.1%), cryptorchism (4.3%).

The registry reports serious adverse events by age group, giving the number at risk, the number affected by serious adverse events, and deaths. The recorded figures are 12 at risk and 2 affected for Younger Children (0 - 6 Years); 23 at risk and 4 affected for Older Children (7 - 12 Years); 14 at risk and 1 affected for Adolescents (13 - 17 Years); and 6 at risk and 0 affected for Adults (18 - 70 Years). Deaths are reported as 0 in each group. These are the registry’s descriptive counts, not estimates from a comparative analysis.

The record also lists serious-event terms with percentages: Catheter site infection, Tourette's disorder and Viral upper respiratory tract infection at 8.3% each; Haemoptysis at 7.1%; and Cryptorchism and Food poisoning at 4.3% each. The registry information does not provide enough detail to infer event timing, duration, recurrence, attribution to treatment or how the percentages were calculated. A listed serious event does not by itself establish causation.

The age-group denominators do not align with the registry’s stated enrollment of 25, and no explanation is reported. They should be read in their recorded age-group context rather than combined into an overall total. The registry does not report a full analysis of adverse-event risk or a comparator group for judging differences.

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

The record establishes what the trial set out to assess: safety, efficacy and pharmacokinetics of nonacog beta pegol in previously treated children with haemophilia B. It also specifies a primary antibody endpoint, its threshold and its observation period. These details make the intended outcome understandable, but they are not the endpoint finding. The number of participants meeting the primary endpoint definition is not reported in the registry record.

The record does not establish whether inhibitory antibodies occurred, how frequently they occurred, or how precise an estimate would be. In general, an event count should be interpreted with its population denominator and, where available, an uncertainty interval. Neither the primary endpoint count nor its uncertainty is reported. The absence of a result in the registry record is not evidence that no events occurred.

The design is single-group and unmasked, with no comparator described. Accordingly, the record does not provide a randomized estimate of how outcomes differ between nonacog beta pegol and another treatment or no treatment. Descriptive observations from a single group cannot isolate the intervention’s contribution from other influences. The registry information also does not support a conclusion about efficacy because results for the listed bleeding and haemostatic outcomes are not reported.

Some serious-adverse-event counts are reported by age group, along with selected event terms and percentages. These describe safety information recorded in the registry, but they do not establish cause or comparative risk. The age-group denominators differ from the stated enrollment, and the record does not explain that discrepancy. The safety figures therefore need to be read with that limitation in mind.

The trial’s broader importance is that it addresses safety, efficacy and drug exposure in the population described by its title and summary. The registry entry alone, however, supplies insufficient outcome results to determine what the trial found. It is appropriate to distinguish the research question, the endpoint definition, and the reported evidence: the first two are described, while the primary endpoint result and the listed efficacy and pharmacokinetic results are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable for the contrast between a specific endpoint definition and the limited outcome reporting in the registry record. The primary endpoint is defined as a participant count based on a stated assay threshold and observation period. That clarity identifies what a result would mean, but without the count, denominator and uncertainty estimate, readers cannot assess the observed endpoint or its precision.

The single-group design also shapes the questions the data can answer. In general, a single-group study can describe outcomes among participants exposed to an intervention, but it does not provide the randomized treatment contrast that a control group can support. This distinction is important when reading the registry’s stated aims of evaluating safety, efficacy and pharmacokinetics: those aims do not themselves establish that comparative effects were estimated.

The record’s planning illustration is another useful statistical distinction. It is described as a planning exercise using assumptions about significance level, allocation, approximation and the effect to detect. Planning calculations concern a hypothetical study design; they are not observed power and do not replace the results of the completed trial. The trial’s own sample-size justification is not reported in the registry record.

Finally, the serious-adverse-event reporting illustrates why denominators and population definitions matter. Counts are presented by age group, but those denominators do not align with the listed enrollment and the record does not explain why. Rather than reconciling the figures by assumption, interpretation should retain their stated context and acknowledge the unresolved discrepancy. Together, these points show why endpoint definitions, analysis populations, uncertainty and design are all necessary when interpreting clinical-trial evidence.

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 interpretation is that the registry record does not report the primary endpoint result. It also does not report a confidence interval or another measure of uncertainty for that endpoint. Consequently, neither the observed antibody count nor its precision can be assessed from the record.

The design is single-group, with masking listed as none and allocation as not applicable. No comparator is described, so the record does not provide a randomized treatment contrast. Results from a single group would be descriptive rather than a direct estimate of a comparative effect. The registry does not report the statistical analysis plan or the methods used to analyse the primary endpoint.

The stated enrollment is 25, while the reported serious-adverse-event age-group denominators are 12, 23, 14 and 6. The record does not explain this inconsistency. The age-group values should not be combined or treated as a reconciled analysis population. The record also does not report how missing data, incomplete follow-up or participants without evaluable assay results were handled.

The registry lists 29 outcome measures but no statistical analyses. It does not report how multiplicity was addressed, whether sensitivity analyses were performed, or whether outcome analyses used adjustments. The secondary outcomes are listed without results, including measures of bleeding, haemostatic response and pharmacokinetics. The trial’s sample-size justification is not reported; the described planning illustration is not a substitute for it. These gaps limit conclusions about both the trial’s findings and the methods used to reach them.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety, Efficacy and Pharmacokinetics of NNC-0156-0000-0009 in Previously Treated Children With Haemophilia B. — NCT01467427.
• Registry record last updated 2025-12-23; status last verified 2025-12.
• Results first posted 2017-11-17.
• 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

NCT01467427 is a completed Phase 3, single-group trial of nonacog beta pegol in previously treated children with haemophilia B. The registry lists enrollment as 25, masking as none, and the intervention as nonacog beta pegol. The record gives a start date of 2012-05-16 and a primary completion date of 2023-11-17, and describes the study as conducted in Asia, Europe and North America.

The primary endpoint is the count of participants developing inhibitory antibodies against FIX at a titre above or equal to 0.6 BU from week 0 to week 52, in the Safety analysis set of participants exposed to the intervention. The primary result is not reported in the registry record. Selected serious-adverse-event counts are listed by age group, but their denominators do not align with the stated enrollment, and the discrepancy is not explained.

The registry lists 29 outcome measures and no statistical analyses. It does not report the statistical analysis plan, the trial’s sample-size justification, or results for the listed secondary efficacy and pharmacokinetic outcomes.