This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study to Evaluate the Efficacy and Safety of PF-07055480 / Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults (NCT04370054), a na phase 3 study. The primary outcome is Total Annualized Bleeding Rate (ABR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04370054 |
| Phase | Phase 3 |
| Condition | Hemophilia A |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 77 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Adult male participants with moderately severe to severe hemophilia A, described in the official title as having FVIII:C of 1% or less. Participants were eligible after follow-up on routine FVIII prophylaxis in the lead-in study. The efficacy population was defined using completion of lead-in follow-up and follow-up or discontinuation in the main study; the registry record does not report the number included in that efficacy analysis.
Intervention
A single administration of PF-07055480, also called giroctocogene fitelparvovec, a recombinant AAV2/6 human Factor VIII gene therapy. The study evaluated the intervention after infusion, with the primary endpoint timeframe beginning at Week 12.
Comparator
There was no randomized concurrent control group. The study describes participants’ total annualized bleeding rate during prior FVIII prophylaxis, using lead-in study data, and after infusion in the current study. This before-and-after comparison is not equivalent to a randomized comparison between treatments.
Primary question
What was the mean total annualized bleeding rate, including treated and untreated bleeds, during the post-infusion period compared with the pre-infusion period on FVIII prophylaxis? The registry record identifies this as the primary endpoint but does not report the group means, confidence intervals, or a statistical test result. Therefore, the magnitude and precision of the observed comparison cannot be described from the registry record.
3. Trial Design
This is a Phase 3, open-label, single-group study of PF-07055480, also called giroctocogene fitelparvovec. The intervention is described as a single intravenous infusion of recombinant AAV2/6 human Factor VIII gene therapy. The registry record reports an enrollment of 77 and lists the study as active, not recruiting. The stated study duration in the brief summary is 5 years.
Because the study has a single group and no masking, it does not compare the intervention with a concurrently randomized control group. Its primary endpoint instead uses two observation periods: a pre-infusion period during routine FVIII prophylaxis, with data collected from a lead-in study, and a post-infusion period in the current study. The registry record gives different follow-up windows for these periods. Pre-infusion follow-up ranged from a minimum of 7.4 months to a maximum of 32.3 months. Post-infusion assessment began at Week 12 and continued through at least 15 months of follow-up, with a maximum follow-up of 44.4 months.
The primary endpoint is total annualized bleeding rate, or ABR, calculated from treated and untreated bleeds and expressed as total bleeds per year. Secondary outcomes include treated ABR, total ABR by cause or location, FVIII activity, exogenous FVIII infusion rate, and annualized FVIII consumption. The registry record lists 43 outcome measures and 5 analyses, but does not report a full statistical analysis plan or identify the methods used for each analysis.
The efficacy analysis population was described as dosed participants who completed at least 6 months of follow-up in the lead-in study and at least 15 months of follow-up in the main study, or who discontinued from the main study before the data cutoff. The record does not report the resulting efficacy analysis count or explain further how discontinuation was handled.
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: Results are presented for primary outcome measures and only those secondary outcome measures whose analysis was complete on a data cutoff date of 17 June 2024 (primary completion date \[PCD\]). Remaining outcome measures would be reported upon completion of their analyses at study completion date.
Treatment Phase
| Stage | PF-07055480 |
|---|---|
| STARTED | 77 |
| Treated | 75 |
| COMPLETED | 75 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | PF-07055480 |
|---|---|
| Lost to Follow-up | 1 |
| Withdrawal by Subject | 1 |
Follow-Up Phase
| Stage | PF-07055480 |
|---|---|
| STARTED | 75 |
| COMPLETED | 0 |
| NOT COMPLETED | 75 |
Reasons for not completing this period:
| Reason | PF-07055480 |
|---|---|
| Ongoing | 75 |
Analysis population for the primary outcome, as defined in the registry: Efficacy analysis population included all participants in the 'Dosed' population \[enrolled and received the study intervention\] who completed at least 6 months of follow up in the lead-in study and at least 15 months of follow-up or discontinued from the study C3731003 prior to the data cutoff for reporting. Data within the same participants were compared between Pre and Post infusion (2 groups described below), with different specified periods/durations.
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 set included all participants enrolled in the study and who received the study intervention.
| Characteristic | Unit | PF-07055480 |
|---|---|---|
| Participants analysed | 75 | |
| Age, Continuous | Years | 32.27 (SD 10.441) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 75 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 3 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 59 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 13 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 14 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 5 |
| Race (NIH/OMB): White | Participants | 56 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Total Annualized Bleeding Rate (ABR), measured over FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Total bleeds per year |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is total annualized bleeding rate, expressed as total bleeds per year. It includes treated and untreated bleeding events. A treated bleed was defined as an event requiring coagulation factor within 72 hours of bleeding signs or symptoms; an untreated bleed did not require coagulation factor within that period.
Annualization expresses bleeding frequency on a per-year scale even when participants have different lengths of observation. The registry describes separate calculations for the pre-infusion and post-infusion periods. The pre-infusion rate uses the number of bleeding episodes and days of follow-up. The post-infusion calculation starts from the infusion date and excludes the first 77 days, with the endpoint timeframe described as beginning at Week 12. These details matter when interpreting the comparison: the two estimates refer to defined observation windows, not necessarily identical periods of follow-up.
ABR is used to summarize recurrent bleeding over time. A rate can capture repeated events, unlike an endpoint that records only whether any event occurred. However, a mean ABR does not by itself describe how rates vary across participants or whether a small number of participants account for many events. The registry record specifies a mean and a 95% confidence interval as the summary format, but does not report the primary endpoint estimates or the interval limits. The observed rate difference and its precision therefore cannot be assessed from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question and endpoint definition, but it does not report the primary endpoint results. It gives no pre-infusion or post-infusion mean total ABR, no 95% confidence interval limits, and no test statistic or p-value for the primary comparison. As a result, the direction, size, and statistical precision of the observed primary endpoint comparison are not reported in the registry record. No conclusion about the endpoint’s observed change can be drawn from the record alone.
The design also shapes what a comparison can mean. Participants’ prior FVIII prophylaxis period is the reference period, with data drawn from a lead-in study; the post-infusion period occurs in the current study. This is a within-participant, before-and-after framework as described, not a randomized, concurrent comparison. Differences between periods can reflect the intervention and also differences in observation time, study context, or other factors. A single-group design cannot separate those potential influences in the way a randomized concurrent control group is intended to do.
Annualization is useful because the pre-infusion and post-infusion windows could differ in length. The endpoint calculation converts event counts and follow-up time into a yearly rate. This makes the measure interpretable as a rate, but it does not remove uncertainty caused by event variability, unequal observation windows, or differences in how data were collected across the lead-in and main study. The registry record describes the calculation but does not provide enough result detail to assess the extent of that uncertainty.
The efficacy population definition is also relevant. It includes dosed participants meeting the stated lead-in and main-study follow-up conditions, with an alternative for those who discontinued before the data cutoff. The registry record does not report how many participants met this definition, the amount of missing endpoint data, or the analytic handling of missing observations. The enrollment figure cannot be treated as the denominator for the primary efficacy result.
Safety reporting is separate from the primary efficacy question. The record lists participants at risk and affected for serious and other adverse events, as well as selected serious-event terms and percentages. These figures describe reported safety events in the registry record; they do not establish causation or provide the clinical context needed to interpret each event. In particular, the record does not report event-level details, timing, severity beyond the serious classification, or attribution to the intervention.
Overall, the available registry information supports a description of the design, endpoint, analysis population criteria, and selected safety figures. It does not supply the primary numerical results needed to characterize the efficacy estimate. Any comparison of observed endpoint values, or any judgment about their precision, would require results that are not reported in the registry record.
9. Statistical Methods Explained
The endpoint is a mean of a continuous measure: total annualized bleeding rate. The registry specifies a 95% confidence interval as the dispersion summary. General explanation: a confidence interval describes the range of values compatible with the data and the statistical method used, and indicates the precision of an estimate. A narrower interval generally indicates greater precision than a wider interval. The interval does not by itself determine whether a difference is clinically important. In this case, neither endpoint means nor interval limits are reported in the registry record, so precision cannot be evaluated.
What does annualizing a rate do?
The registry defines total ABR by scaling the number of bleeding episodes according to the number of days observed. This expresses event frequency on a per-year scale. General explanation: rate standardization can help compare observation periods of different lengths, because a participant observed for less time does not automatically contribute a lower rate simply by having less time in which events could be recorded. Annualization does not make short and long observation periods identical, however. It relies on the rate being a useful representation of the observed period, and event counts can be variable, particularly when events are infrequent or cluster in time.
The registry gives separate formulas for pre-infusion and post-infusion ABR. The pre-infusion calculation uses bleeding episodes during the prior prophylaxis period and days of follow-up. The post-infusion calculation uses the period after infusion with the first 77 days excluded; the endpoint timeframe is described as beginning at Week 12. These definitions should be read alongside the distinct follow-up windows: pre-infusion follow-up ranged from 7.4 to 32.3 months, while post-infusion assessment extended from Week 12 through at least 15 months, with maximum follow-up of 44.4 months. The record does not report individual observation times or the distribution of follow-up.
Why include both treated and untreated bleeds?
The primary endpoint counts both types. The registry defines a treated bleed as one for which coagulation factor was administered within 72 hours of signs or symptoms; an untreated bleed did not prompt factor administration within that interval. Including both categories means the endpoint is not limited to events that led to treatment. General explanation: event definitions are important because changes in care-seeking or treatment decisions could affect whether an event is classified as treated, even when the underlying occurrence of symptoms is similar. The record does not report further adjudication procedures or how event classification was verified.
What does the single-group comparison allow?
The primary question compares the post-infusion period with the prior FVIII prophylaxis period. This is not a randomized comparison between parallel groups. General explanation: random assignment to concurrent groups is used to make treatment groups comparable, on average, with respect to both measured and unmeasured factors. A before-and-after comparison instead uses each participant’s earlier period as a reference, but can be affected by changes over time, differences in study procedures, or other circumstances. The registry record does not report a statistical adjustment that addresses such differences, and no adjustment should be assumed.
Open-label describes the lack of masking. General explanation: when participants and study personnel know which intervention is being administered, some outcomes may be more susceptible to expectations or differences in recording and management. The primary endpoint includes bleeding events, and the registry describes definitions for treated and untreated events, but it does not report whether outcome assessment was blinded or independently adjudicated.
How should the efficacy population be understood?
The record defines the efficacy analysis population using participants who were dosed, completed at least 6 months of lead-in follow-up, and completed at least 15 months of main-study follow-up, or discontinued before the data cutoff. This definition is not the same as enrollment. General explanation: analysis populations determine which participants contribute to an estimate, and their definition can affect how broadly a result applies. The registry record does not report the count in this population, the number excluded, or the reasons for any exclusions. It also does not explain how missing endpoint observations were treated.
What can be inferred from a mean rate?
A mean summarizes the average rate across the analysis population, but it may not show the distribution of individual rates. General explanation: recurrent-event outcomes can be over-dispersed when event counts vary more than a simple model expects. If that occurs, a model that assumes less variability can produce confidence intervals that are too narrow. The registry record does not identify the model used for the primary endpoint or report an assessment of over-dispersion. It would therefore be inappropriate to claim that a particular model or variance adjustment was used.
The registry record gives an endpoint summary format of mean with a 95% confidence interval, but does not provide the estimates. It also does not report a p-value, adjusted analysis, or detailed methods for calculating uncertainty. Those omissions prevent evaluation of the statistical procedure and its assumptions.
What is known about planning illustrations?
General explanation: sample-size calculations for a future study can illustrate the number of participants per arm associated with a chosen power under specified assumptions. Such calculations are planning illustrations, not observed power and not evidence about the precision of the completed study. The registry describes an illustrative approach based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. These assumptions do not describe the design of this single-group trial, and the registry record does not report a trial-specific sample-size justification.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 43 outcome measures and 5 analyses. It identifies total ABR as the primary endpoint and lists secondary outcomes that include treated ABR, FVIII activity, exogenous FVIII infusion rate, annualized FVIII consumption, and total or treated ABR classified by cause or location. The record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a detailed plan distinguishing confirmatory from exploratory analyses. It is therefore not possible to determine from the registry record how the risk of false-positive findings across multiple analyses was addressed.
The record reports the efficacy analysis population criteria but not the number of participants included in that analysis. It does not report the number with missing primary endpoint data, reasons for missingness, or a method for handling missing observations. It also does not describe sensitivity analyses for missing data. These details matter because conclusions from an analysis can depend on who contributes data and how incomplete follow-up is handled.
The population definition specifies that participants were dosed, completed at least 6 months in the lead-in study, and completed at least 15 months in the main study, or discontinued before the data cutoff. The registry record does not clarify how the alternative discontinuation criterion was implemented in the primary analysis, nor whether all available follow-up contributed to the rate calculation for those participants. It also does not report whether the analysis was adjusted for any baseline characteristics or other variables. Those procedures are not reported in the registry record and should not be inferred.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| PF-07055480 | 15 | 75 | 20.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| PF-07055480 | 0 of 75 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| PF-07055480 | 70 of 75 |
Most frequent serious adverse event terms
| Event term | Organ system | PF-07055480 |
|---|---|---|
| Pyrexia | General disorders | 5 of 75 |
| Anti factor VIII antibody positive | Investigations | 2 of 75 |
| Transaminases increased | Investigations | 2 of 75 |
| Ocular hyperaemia | Eye disorders | 1 of 75 |
| Pancreatitis acute | Gastrointestinal disorders | 1 of 75 |
| Chills | General disorders | 1 of 75 |
| Facial pain | General disorders | 1 of 75 |
| Swelling face | General disorders | 1 of 75 |
| Immune-mediated adverse reaction | Immune system disorders | 1 of 75 |
| COVID-19 | Infections and infestations | 1 of 75 |
Most frequent non-serious adverse event terms
| Event term | Organ system | PF-07055480 |
|---|---|---|
| Pyrexia | General disorders | 45 of 75 |
| Headache | Nervous system disorders | 38 of 75 |
| Alanine aminotransferase increased | Investigations | 37 of 75 |
| Nausea | Gastrointestinal disorders | 23 of 75 |
| Factor VIII activity increased | Investigations | 18 of 75 |
| Chills | General disorders | 16 of 75 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 16 of 75 |
| Aspartate aminotransferase increased | Investigations | 13 of 75 |
| Fatigue | General disorders | 11 of 75 |
| Upper respiratory tract infection | Infections and infestations | 11 of 75 |
Serious events with the highest arm-level rate: pyrexia (6.7%), anti factor viii antibody positive (2.7%), transaminases increased (2.7%), ocular hyperaemia (1.3%), pancreatitis acute (1.3%).
The registry reports serious adverse event figures for the PF-07055480 group: 75 participants were at risk, 15 were affected, and deaths were reported as 0. For other adverse events, the record lists 75 participants at risk and 70 affected. These are registry counts, not estimates of causal risk attributable to the intervention. The record does not provide the event-level timing, duration, outcome, or attribution needed to interpret individual cases.
The listed serious adverse event terms include pyrexia at 6.7%, anti factor VIII antibody positive at 2.7%, transaminases increased at 2.7%, ocular hyperaemia at 1.3%, pancreatitis acute at 1.3%, and chills at 1.3%. These percentages are reported as registry figures; the record does not explain in this summary whether terms can overlap within participants or give corresponding event counts. They should not be added together.
Serious adverse events and other adverse events are different reporting categories, and the affected counts should not be conflated. A count of affected participants does not describe how many events each participant experienced. The registry record also does not provide a comparison group, so these safety figures do not establish whether event frequency differs from what would have occurred without the intervention.
12. What the Result Does, and Does Not, Mean
The registry record describes a Phase 3, open-label study evaluating a single infusion of PF-07055480 in adult men with moderately severe to severe hemophilia A. Its primary endpoint is total annualized bleeding rate, including treated and untreated bleeding events. The endpoint compares a post-infusion period with a prior period on FVIII prophylaxis, using data from a lead-in study for the earlier period.
What the record does not establish is the numerical primary endpoint result. It does not report the mean rates for either period, the 95% confidence intervals, or a statistical test result. Without those values, the observed change and its precision cannot be described. The record therefore supports an explanation of what was planned and measured, but not a conclusion about the primary endpoint’s observed magnitude.
The design is single-group rather than randomized against a concurrent control. A before-and-after comparison can provide information about participants’ experience across the two specified periods, but it does not have the same protection against time-related differences and other influences as a randomized comparison. The registry record does not report an adjustment that would resolve those limitations.
The efficacy population criteria and safety counts add context, but they do not fill the gap in primary efficacy results. Enrollment is not interchangeable with the efficacy analysis population, whose size is not reported. Safety figures describe recorded events in the study group; they do not, on their own, establish that an event was caused by the intervention or indicate how the study’s safety experience compares with an alternative.
Accordingly, interpretation should remain limited to the study design, endpoint definitions, follow-up windows, population criteria, and safety data that the registry record reports. Primary outcome estimates, analysis details, and missing-data procedures are not reported in the registry record, so they cannot be used to support further statistical conclusions.
13. Why This Trial Matters Statistically
This study is statistically notable for measuring a recurrent-event outcome across two periods with different roles: prior FVIII prophylaxis in a lead-in study and post-infusion follow-up in the main study. Expressing bleeding as an annualized rate allows event frequency to be described on a common time scale, while the specified observation windows make clear that the underlying periods are not identical. Interpreting such a comparison requires attention to both the rate calculation and the design that generated the data.
The single-group structure is central to statistical interpretation. A prior treatment period can provide useful context for a within-participant comparison, but it is not a randomized concurrent control. The observed association between period and rate, if reported, would need to be interpreted with that limitation in mind. The registry record does not report the endpoint results, so the actual size and precision of the primary comparison cannot be assessed.
The record also highlights why analysis-population details matter. Eligibility for the efficacy analysis depends on specified follow-up and discontinuation criteria, yet the size of the resulting population is not reported. Without that count and information about missing data, readers cannot judge how complete the endpoint evidence is or how the analysis population relates to enrollment.
Finally, the registry lists multiple outcomes and analyses without reporting a multiplicity strategy. That omission limits interpretation of any secondary findings that may appear elsewhere in the record. For statistical readers, the main lesson is that design, outcome definition, follow-up, population criteria, and reporting completeness jointly determine what a result can support. In this registry record, the methods framework is described more fully than the primary numerical results.
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 for interpreting efficacy is that the registry record does not report the primary ABR estimates or their 95% confidence intervals. It also does not report a p-value or other test result. The endpoint is defined, but its observed value and precision are unavailable in this record.
The study is open-label and single-group. The comparison uses a pre-infusion period on FVIII prophylaxis and a post-infusion period after gene therapy rather than a randomized concurrent control. Differences between the periods could therefore reflect factors other than the intervention. The registry record does not report a statistical adjustment that addresses these potential differences.
Follow-up windows differ between the pre-infusion and post-infusion periods, and the endpoint calculation treats them according to separate definitions. The record does not report individual follow-up durations, the distribution of event counts, or the model used to estimate uncertainty. It also does not report whether recurrent-event variability was assessed or addressed.
The efficacy population is defined by follow-up criteria, but the number analyzed, exclusions, missing endpoint data, and missing-data methods are not reported in the registry record. The description of the population criteria does not establish how all participants’ available data contributed to the primary analysis.
Finally, the record lists multiple outcomes and analyses but does not report a multiplicity plan, detailed analysis methods, or an explanation of how safety events were attributed to the intervention. These reporting gaps limit assessment of both statistical robustness and the context of the reported safety figures.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate the Efficacy and Safety of PF-07055480 / Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults — NCT04370054.
- Registry record last updated 2026-08-19; status last verified 2026-07.
- Results first posted 2025-08-17.
- 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.
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18. Record Summary
The registry record describes NCT04370054 as an open-label, single-group Phase 3 study of a single administration of PF-07055480, also called giroctocogene fitelparvovec, in adult men with moderately severe to severe hemophilia A. Enrollment is reported as 77, and the study status is active, not recruiting.
The primary endpoint is mean total annualized bleeding rate, including treated and untreated bleeds. It compares a pre-infusion FVIII prophylaxis period with a post-infusion period beginning at Week 12. The record reports the endpoint definitions and follow-up windows but not the primary outcome estimates or confidence interval limits.
The efficacy population is defined by lead-in and main-study follow-up criteria, but its size and missing-data handling are not reported. Safety reporting includes affected-participant counts, deaths, and selected serious adverse event terms. The record does not report a concurrent control group or a detailed statistical analysis plan.