A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B (NCT03861273), a non-randomized phase 3 study. The primary outcome is Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) From Week 12 to Month 15.

2. Clinical Question

3. Trial Design

This was a Phase 3, open-label, non-randomized, single-group study sponsored by Pfizer. The registry lists enrollment of 51 participants and a single intervention, PF-06838435/fidanacogene elaparvovec. Participants received one intravenous dose and were evaluated over 6 years. The study status is active, not recruiting; the recorded start date is 2019-07-29 and the primary completion date is 2022-11-16.

The primary endpoint compares bleeding rates across two periods: the pre-infusion period on FIX prophylaxis in lead-in study C0371004 and the post-infusion period in the current study. The pre-infusion period covers at least 6 months of prospectively collected data up to dosing, with an average duration of 1.31 years. The post-infusion primary measurement window is Week 12 to Month 15. This comparison does not use a separately randomized control group, and the periods are not concurrent.

That design has a direct interpretive consequence: changes between the periods are within-participant, before-and-after observations, not a randomized estimate against a contemporaneous control. Participants serve as their own historical reference, but that does not by itself control for temporal changes or differences in measurement circumstances. The registry does not report additional design details that would explain how such influences were addressed.

The outcome definition excludes surgical procedures from the summaries and analyses. Treated bleeds are defined as bleeding events requiring coagulation factor within 72 hours of signs or symptoms; untreated bleeds do not require factor within that window. The registry lists 27 outcome measures and 11 analyses. It does not report the rationale for the planned enrollment, a detailed statistical analysis plan, or any interim-analysis plan. The primary outcome results themselves 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 51 participants were screened in this study and 45 participants received a single dose of PF-06838435 (fidanacogene elaparvovec). Results presented are for primary outcome measures and only those secondary measures whose analysis was complete on a data cutoff date of 16 November 2022 (primary completion date \[PCD\]).

Screening Phase (3 Weeks)

Reasons for not completing this period:

Treatment Phase (Day 1)

Follow-up Phase (Year 1)

Reasons for not completing this period:

Long-Term Follow-Up (Year 2 to Year 6)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion.

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 included all participants enrolled in the study and who received PF-06838435 infusion.

6. Primary Endpoint

The registry lists the primary outcome as Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) From Week 12 to Month 15, measured over Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm).

The primary endpoint is the annualized bleeding rate (ABR) for total treated and untreated bleeds. It measures the frequency of bleeding episodes over time, expressed as total bleeds per year. Annualization allows periods of different lengths to be represented on a common time scale; it does not mean that each participant was observed for a full year within the specified analysis window.

The registry defines ABR as the number of total bleeding episodes during the period multiplied by 365.25 and divided by the elapsed calendar days, including the first and last day of that period. Surgical procedures are excluded. A treated bleed is an event requiring coagulation factor within 72 hours of signs or symptoms. An untreated bleed is one that does not require factor within that timeframe.

Bleeding rate is relevant to this study because the stated main objective is to evaluate ABR after gene therapy in comparison with the participants’ pre-infusion FIX prophylaxis period. The primary outcome uses the mean ABR and a 95% confidence interval. General statistical interpretation: a confidence interval conveys uncertainty around an estimated quantity; it does not ensure that the underlying comparison is free of bias. The numerical ABRs and interval limits are not reported in the registry record, so the estimated size and precision of the comparison cannot be assessed from these registry entries.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary outcome as a continuous measure summarized by a mean and 95% confidence interval. The endpoint is an annualized rate: bleeding episodes are counted within a specified observation period and scaled to a year using the registry’s stated formula. Surgical procedures are excluded. Treated and untreated bleeds are both included in the primary total, with the distinction based on whether coagulation factor was administered within 72 hours of bleeding signs or symptoms.

What does annualization mean?

General statistical explanation: annualization expresses an event rate on a common time scale when people have observation periods of different lengths. It makes rates easier to compare than raw counts alone when follow-up duration varies. It does not transform a short observation window into a year of directly observed data, and the rate remains an estimate based on the events and time actually recorded. The registry supplies the calculation rule, but it does not report the individual event counts, person-time, or primary rate estimates.

What does the mean describe?

General statistical explanation: the mean is an average across the observations included in an analysis. It can summarize the overall level of a continuous outcome, but it does not show the distribution of individual participants’ values. For event rates, a mean alone does not reveal whether most participants had similar rates or whether a smaller number of participants had comparatively high rates. The registry does not report distributional summaries for the primary endpoint in the registry record.

How should a confidence interval be read?

General statistical explanation: a confidence interval describes the uncertainty around an estimated quantity according to the method used to calculate it. A narrower interval generally indicates greater statistical precision than a wider interval, but precision is not the same as freedom from bias. An interval for a rate or comparison does not remedy limitations caused by a non-randomized design or a historical comparator. The registry names a 95% confidence interval but does not provide its limits or specify the calculation method in the record.

What does the comparison design permit?

The primary contrast uses pre-infusion FIX prophylaxis observations from lead-in study C0371004 and post-infusion observations in the current study. The design is single-group and non-randomized, so it is not a parallel comparison between randomized groups receiving different treatments. General statistical explanation: within-participant comparisons can account for stable characteristics of the same participant, but they remain vulnerable to changes over time, differences in observation periods, and other factors that change between measurement periods. The registry record does not report a statistical adjustment strategy for these issues.

The pre-infusion period was at least 6 months and averaged 1.31 years. The post-infusion endpoint window ran from Week 12 to Month 15. Because the periods have different timing and duration, the ABR formula scales observed events by time. The registry identifies prospectively collected pre-infusion data and defines the start and end points, but does not report details such as handling of incomplete observation or the exact approach to missing records.

What should be inferred from sample-size illustrations?

The registry entries include assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. These are described as planning illustrations rather than the trial’s design. The actual study is single-arm and does not have equal allocation between two randomized arms. No sample-size justification for this trial is reported in the registry record. The illustration assumptions should therefore not be mistaken for the trial’s recruitment plan, evidence of achieved power, or a description of its primary analysis.

General statistical explanation: power is a design-stage probability of detecting a specified effect under stated assumptions. A sample-size calculation based on an observed effect is a planning exercise and does not establish that a completed study had that probability of detecting its actual effect. It also cannot substitute for the estimated result and its uncertainty. No observed primary effect is included in the registry record, and no power conclusion can be drawn from the enrollment count alone.

The registry lists 27 outcome measures and 11 analyses. It does not report the full model specification, the method for the confidence interval, the treatment of missing outcome data, or a multiplicity strategy. Those omissions limit reproducibility and prevent a detailed appraisal of the statistical procedures beyond the endpoint definition and design features recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 27 outcome measures and 11 analyses. It does not report a multiplicity strategy, such as whether the primary endpoint was tested within a prespecified hierarchy or whether adjustments were made across multiple outcomes. Without that information, the implications of examining multiple outcomes and analyses cannot be assessed. The record does not establish that multiplicity was or was not controlled.

The primary outcome population is the dosed analysis set, defined as enrolled participants who received PF-06838435 infusion. The count in that set is not reported in the registry record. Enrollment is listed as 51, while the adverse-event group lists 45 participants at risk; the record excerpt does not explain how these entries relate or provide a participant flow accounting.

Missing-data methods are not reported in the registry record. The registry entries do not state how incomplete bleeding diaries, gaps in follow-up, or other unavailable outcome observations were handled. Nor do they describe imputation, sensitivity analyses, or assumptions about missingness. These details matter because rate estimates depend on correctly accounting for both events and observed time.

The registry also does not report the primary statistical model or the method used to calculate the 95% confidence interval. Consequently, the exact analysis population, handling of missing measurements, and uncertainty procedure cannot be fully evaluated. These are reporting gaps; they do not by themselves show that a particular method was or was not used.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (4.4%), duodenal ulcer (2.2%), duodenal ulcer haemorrhage (2.2%), upper gastrointestinal haemorrhage (2.2%), drug-induced liver injury (2.2%).

The registry’s adverse-event group for PF-06838435 lists 45 participants at risk, 7 affected by serious adverse events, 37 affected by other adverse events, and 0 deaths. These figures describe the entries in the registry record and should not be read as evidence of causation. The registry record does not provide event timing, exposure-adjusted rates, or a comparator group for safety.

The listed serious adverse-event terms and percentages are Anaemia, 4.4%; Duodenal ulcer, 2.2%; Duodenal ulcer haemorrhage, 2.2%; Upper gastrointestinal haemorrhage, 2.2%; Drug-induced liver injury, 2.2%; and COVID-19, 2.2%. These percentages are reproduced as recorded; the denominator for each term is not stated in the registry record. The terms are not a complete account of every possible adverse event, and the record excerpt does not provide severity grading or detailed event narratives.

General statistical explanation: adverse-event counts describe what occurred in the observed group, while interpreting risk requires attention to the number exposed, duration of observation, event definitions, and the possibility of events unrelated to the intervention. The registry’s single-arm design does not provide a randomized safety comparison. The listed 0 deaths applies to the adverse-event group entry and should not be extended beyond that record.

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

The registry describes a Phase 3 evaluation of PF-06838435 in adult males with moderately severe to severe hemophilia B, using annualized total bleeding rate as the primary outcome. The endpoint compares post-infusion observations with a pre-infusion period on FIX prophylaxis. The design and definitions explain what was intended to be measured, but the numerical primary outcome results are not reported in the registry record.

That absence means the direction and magnitude of the primary comparison cannot be stated. There is no ABR estimate or 95% confidence interval in the registry record, so the statistical precision of the result cannot be evaluated. It is also not possible to assess whether participant-level outcomes were consistent or whether the mean was influenced by a subset of observations.

The before-and-after design can describe differences across the two periods, but it does not provide the same basis for causal interpretation as a randomized concurrent comparison. A change in the observed rate would not, by itself, distinguish intervention effects from other differences over time. The registry entries do not report an adjustment method that would address this limitation.

The safety record lists adverse events among 45 participants at risk, including 7 affected by serious adverse events and 0 deaths. These figures are descriptive, with no randomized safety comparator reported. They do not establish whether an event was caused by the intervention, and they do not fully characterize the timing or duration of risk.

The record therefore supports conclusions about study structure, endpoint definitions, and the reported safety entries, but not a numerical conclusion about the primary bleeding-rate comparison. It also does not support conclusions about long-term outcome values, which are not included in the registry record, despite the planned evaluation over 6 years. The distinction is between a stated research question and the results needed to answer it: the question is clear, while the primary result and its uncertainty are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for comparing a participant’s pre-infusion bleeding experience on FIX prophylaxis with a post-infusion period after a single gene-therapy dose. That design makes the historical reference clinically and analytically important: the primary contrast is not between randomized groups, but between observations collected at different times and in different studies. Understanding that structure is necessary before interpreting any reported change in ABR.

The endpoint itself depends on both event counting and time at risk. Annualization offers a common rate scale, and the registry defines the relevant bleed categories and excludes surgical procedures. Those choices determine what the endpoint represents. They also make clear that the primary measure is not simply a count of all events over the full 6-year evaluation period; the post-infusion primary window is Week 12 to Month 15.

The record also illustrates why an endpoint definition is not a substitute for an outcome estimate. Although the primary measure is specified as a mean with a 95% confidence interval, the numerical rate and interval are not reported in the registry record. Without them, statistical precision and the observed comparison cannot be assessed.

Finally, the registry lists 27 outcome measures and 11 analyses but does not report a multiplicity strategy or missing-data methods. These details affect how readers assess the breadth and reliability of findings. The trial’s design, definitions, and safety entries are informative, while the absent primary outcome values and analysis details constrain statistical interpretation.

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 limitation is that the registry record does not include the ABR estimates, the 95% confidence intervals, or a test result for the primary comparison. Consequently, neither the direction nor the size and precision of the observed comparison can be evaluated.

The comparison is non-randomized, open-label, and single-arm. It uses pre-infusion data from lead-in study C0371004 as a historical reference rather than a concurrent randomized control. Differences between the periods may have explanations other than the intervention, and the registry entries do not describe an adjustment strategy.

The primary analysis population is defined as participants who received infusion, but its size is not reported. Enrollment is 51, whereas the adverse-event group reports 45 at risk; the relationship between these counts is not explained in the registry record. The record also does not report a participant flow account.

Missing-data procedures, the primary model, the confidence-interval method, and multiplicity handling are not reported in the registry record. The outcome list includes 27 measures and 11 analyses, but the registry entries do not describe how analyses were selected or interpreted together.

The study evaluation extends over 6 years, but long-term outcome values are not included in the registry record. The adverse-event entries are descriptive and do not provide a randomized safety comparison, event timing, or exposure-adjusted rates. These limitations restrict interpretation of both efficacy and safety without implying that unreported methods were necessarily absent from the study itself.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B — NCT03861273.
• Registry record last updated 2026-11-04; status last verified 2026-11.
• Results first posted 2024-03-27.
• 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

NCT03861273 is a Phase 3, open-label, non-randomized, single-group study sponsored by Pfizer. It enrolled 51 adult males with moderately severe to severe hemophilia B and evaluated a single intravenous dose of PF-06838435/fidanacogene elaparvovec. The registry lists the study as active, not recruiting, with a start date of 2019-07-29 and primary completion date of 2022-11-16.

The primary outcome is mean annualized total bleeding rate, including treated and untreated bleeds, compared between pre-infusion FIX prophylaxis and Week 12 to Month 15 after infusion. The record describes a 95% confidence interval, but the primary numerical results are not reported in the registry record. The safety group lists 45 participants at risk, 7 affected by serious adverse events, 37 by other adverse events, and 0 deaths.