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 Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients at a Dose of 4E13 vg/kg (NCT03392974), a na phase 3 study. The primary outcome is Change of the Median Factor VIII (FVIII) Activity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03392974 |
| Phase | Phase 3 |
| Condition | Hemophilia A |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | BioMarin Pharmaceutical |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned Hemophilia A patients with residual Factor VIII levels ≤1IU/dL who were receiving prophylactic Factor VIII infusions. The primary outcome population is identified as intention-to-treat. The registry record reports enrollment of 1, but does not describe participant characteristics or provide further detail about the analysis population.
Intervention
The intervention was a single administration of valoctocogene roxaparvovec, also identified as BMN 270, at a dose of 4E13 vg/kg. The study was open label, so masking is listed as none. The registry record describes the treatment and dose but does not report additional details about treatment delivery or adherence.
Comparator
There was no concurrent comparator arm. The study is recorded as single-group, with allocation listed as not applicable. It therefore does not provide a randomized, like-for-like comparison with a control group. The registry record does not report a separate control intervention or a between-group treatment effect.
Primary question
The primary question concerned change in Factor VIII activity at Week 52 after infusion, measured using a chromogenic substrate assay. The study description also identifies Factor VIII activity during weeks 49-52 as an efficacy focus. The registry record does not report a numerical estimate of the primary endpoint, its uncertainty, or a statistical test result, so the magnitude and precision of the observed change cannot be assessed from this record.
3. Trial Design
This was a Phase 3, open-label, single-arm study of valoctocogene roxaparvovec in Hemophilia A. The intervention is described as one administration at a dose of 4E13 vg/kg. The official study title identifies patients with residual Factor VIII levels ≤1IU/dL who were receiving prophylactic Factor VIII infusions. The registry record lists BioMarin Pharmaceutical as sponsor and the study status as completed.
With a single group and no masking, the study design is not a randomized comparison against a concurrent control. Allocation is listed as not applicable. The record reports enrollment of 1. This enrollment figure is important context for reading both efficacy and safety information: it does not support a broad assessment of variation across a larger group, and the record offers no comparative estimate of treatment effect against another arm.
The primary outcome is described as change in Factor VIII activity, measured by chromogenic substrate assay at Week 52, with the primary population identified as intention-to-treat. The brief study summary describes efficacy assessment during weeks 49-52 and also mentions exogenous Factor VIII replacement use and bleeding episodes from week 5 to week 52. The secondary outcomes concern change in annualized Factor VIII utilization and change in the annualized number of bleeding episodes requiring replacement treatment.
The registry record gives the study start as 2018-03-14 and primary completion as 2019-05-22. It does not report a protocol-based rationale for the enrollment, details of the statistical analysis plan, or whether any interim analyses were planned or performed. Those design features cannot be inferred from the phase, the stated endpoint, or the fact that the study is marked completed.
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
| Stage | BMN 270 4E13 vg/kg |
|---|---|
| STARTED | 1 |
| COMPLETED | 1 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Intention-to-treat
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.
| Characteristic | Unit | BMN 270 4E13 vg/kg |
|---|---|---|
| Participants analysed | 1 | |
| Age, Continuous | years | 45.0 (SD NA) |
| Age, Customized: 18 - <65 | participants | 1 |
| Age, Customized: >= 65 | participants | 0 |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | participants | 0 |
| Race/Ethnicity, Customized: Asian | participants | 0 |
| Race/Ethnicity, Customized: Native Hawaiian or Other Pacific Islander | participants | 0 |
| Race/Ethnicity, Customized: Black or African American | participants | 0 |
| Race/Ethnicity, Customized: White | participants | 1 |
| Race/Ethnicity, Customized: Other | participants | 0 |
| Region of Enrollment: United States | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Change of the Median Factor VIII (FVIII) Activity, measured over Week 52.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | IU/dL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is titled “Change of the Median Factor VIII (FVIII) Activity” and uses IU/dL. Its description specifies change in Factor VIII activity at Week 52 after BMN 270 infusion, measured with a chromogenic substrate assay. The brief study summary separately describes efficacy in terms of Factor VIII activity during weeks 49-52. These descriptions establish the measurement and timing, but the registry record does not provide the numerical activity values or the numerical change.
Factor VIII activity is a continuous measurement. In general, continuous endpoints can retain information about the magnitude of a measured response rather than reducing it to a yes-or-no outcome. A change endpoint also focuses attention on how a measurement differs from its reference value. The registry record does not specify the reference value or the exact calculation used to derive change, so these details should not be assumed.
There is a reporting distinction to keep in mind: the endpoint title refers to a median, while the analysis description identifies the parameter as a mean with standard deviation. The record does not explain this difference or identify which summary was used for the posted endpoint result. Since no numerical primary result is reported in the registry record, neither the central estimate nor its precision can be evaluated. The assay and timepoint alone do not establish the size or reliability of a change.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a planned efficacy assessment centered on Factor VIII activity at Week 52, alongside changes in replacement therapy use and bleeding episodes. However, it does not report numerical results for these efficacy outcomes. There is therefore no estimate in the record from which to describe the observed size of a change, its variability, or the precision of an estimated effect. The study description and endpoint definition should not be mistaken for outcome results.
The record identifies the study as a single-group study with no masking and no concurrent comparator. This matters for interpretation: observations after treatment can be described, but the design does not directly estimate how those observations compare with outcomes under a control intervention. Without a like-for-like control group, the registry record cannot separate a treatment-associated change from other possible explanations for a change over time. This is a design limitation, not a numerical finding about efficacy.
Enrollment is listed as 1. That makes the scope of any observed data especially limited: a measurement from a single enrolled participant cannot describe the distribution of responses across a broader population. The record does not give a participant-level primary endpoint result, so even an individual change cannot be assessed from the information recorded. No confidence interval, standard error, p-value, or other uncertainty estimate is reported for the efficacy outcomes.
The endpoint terminology also requires care. The primary title says “median,” whereas the analysis description names a mean and standard deviation. A median and a mean summarize a distribution in different ways, and the record does not reconcile the terminology. The analysis parameter alone does not resolve which summary was used to report the endpoint. As no endpoint value is available, neither summary can be interpreted for this study from the registry record.
The secondary outcomes are changes in annualized use of exogenous Factor VIII and in the annualized number of bleeding episodes requiring replacement treatment. These are clinically relevant utilization and event measures, but the registry record gives no numerical estimates or uncertainty for them. Their presence in the study description indicates what was intended to be assessed, not what was observed.
Overall, the posted record supports a description of study design, outcome definitions, and adverse-event counts. It does not support a conclusion about the size, precision, or comparative effect of treatment on Factor VIII activity, Factor VIII use, or bleeding episodes. A completed status means the study is recorded as completed; it does not substitute for numerical outcome reporting.
9. Statistical Methods Explained
What does a single-arm design estimate?
In general, a single-arm study follows a group receiving an intervention and describes outcomes in that group. It can document measurements at specified times and changes relative to a defined reference, if those results are reported. It does not, by itself, supply a concurrent control outcome. A randomized comparison is designed to compare groups under assigned interventions; a single-group study cannot make that same direct contrast. Here, the registry record classifies the model as single-group, lists allocation as not applicable, and records no masking.
This distinction limits causal interpretation. If an outcome changes after an intervention, a single-arm record can show the observed temporal pattern if measurements are available. But without a concurrent comparator, the change cannot be directly contrasted with what would have happened under another intervention or no intervention. General methodological considerations such as natural variation, time trends, and measurement variation are reasons that before-and-after observations do not automatically establish a causal effect. These are general cautions, not reported explanations for any result in this study.
What does the endpoint summary mean?
The primary outcome is a continuous Factor VIII activity measurement in IU/dL, assessed at Week 52 using a chromogenic substrate assay. The registry record describes a change endpoint and identifies intention-to-treat as the primary population. In general, a mean summarizes the arithmetic center of measured values, while a median identifies the middle value after ordering the observations. A standard deviation describes spread around a mean under the usual interpretation. These summaries are not interchangeable, especially when a distribution is skewed or affected by extreme observations.
The registry endpoint title refers to a median, but its analysis description specifies a mean and standard deviation. The record does not explain this difference. It also does not report the actual endpoint estimate, standard deviation, sample contributing to the analysis, or an uncertainty interval. Consequently, there is no basis to decide which summary was used in the reported analysis or to assess the observed response distribution.
In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. Its width reflects both the observed variability and the information available for estimation. A point estimate without an uncertainty interval gives less information about precision; here, the registry record reports neither a primary estimate nor an interval. No significance test result is reported either. The absence of these quantities in the registry record should not be treated as evidence that an effect is absent or that an effect is statistically significant.
How should secondary outcomes be understood?
The registry record lists changes in annualized utilization of exogenous Factor VIII replacement therapy and in annualized bleeding episodes requiring replacement treatment. Annualized measures express frequency or use in relation to a time period, which can make observations over differing follow-up durations more comparable when the calculation is specified. In general, such measures require clear definitions of the counting period, eligible events, and handling of incomplete follow-up. The registry record does not provide the formulas or numerical secondary outcome results, so those details cannot be assessed.
The brief study summary describes assessment of Factor VIII activity during weeks 49-52 and monitoring of replacement therapy use and bleeding episodes from week 5 to week 52. These time windows give context for the intended outcome assessments. They do not establish how observations outside those periods were handled, how missing observations were treated, or whether all listed outcomes were analyzed as specified. Those analysis details are not reported in the registry record.
What do planning illustrations represent?
In general, a sample-size planning illustration asks how many participants per arm might be needed under chosen assumptions to detect a specified effect with a chosen type I error rate and power. The planning assumptions recorded for this study describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as stated fractions of the observed effect. For time-to-event outcomes, the note says that the planning quantity is total events; other outcomes use participants per arm.
Those assumptions are explicitly described as a planning illustration computed from the observed effect, not as the trial's own design. They do not establish that the study enrolled the illustrated sample size or had a particular achieved power. The registry record does not report the trial's sample-size justification, and no planning result values are included in the record. Any such illustration is hypothetical and depends on its assumptions; it cannot repair the lack of a comparator or replace reported outcome estimates.
Over-dispersion is a general concern when count outcomes vary more than a simple model assumes. If present, it can make standard errors too small when the analysis ignores the extra variability. This is relevant in principle to event counts such as bleeding episodes, but the registry record does not report a model, a dispersion assessment, or an analysis of those counts. It would therefore be inappropriate to claim that over-dispersion occurred or was addressed in this study.
What is not available for evaluating the analyses?
The registry record lists three outcome measures and zero analyses. It does not report numerical outcome estimates, uncertainty intervals, test statistics, analysis details for missing observations, interim analyses, or the full statistical plan. The primary population is identified as intention-to-treat, but the record does not explain how that population was defined or how deviations from the intended treatment were handled. These omissions constrain assessment of both the analysis conduct and the precision of the results.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary outcome and secondary outcomes concerning annualized Factor VIII use and bleeding episodes. It reports three outcome measures and zero analyses. It does not describe a multiplicity strategy, such as how interpretation would account for testing more than one outcome or multiple timepoints. A prespecified strategy can help distinguish a primary confirmatory question from additional analyses and can control the chance of false-positive conclusions across tests. This is a general statistical consideration; the registry record does not say whether such a strategy was included elsewhere in the protocol.
The record identifies the primary population as intention-to-treat. It does not report the operational definition of that population, the number of participants with endpoint data, or how missing measurements were handled. It also does not say whether missingness was assessed, whether any imputation was used, or how sensitivity analyses were conducted. These details are important because methods for incomplete data can affect estimates and their uncertainty. In their absence, no assumption about the missing-data approach is warranted.
The record also does not report a detailed statistical analysis plan, interim analyses, or outcome-specific analysis methods. The fact that the study is marked completed does not establish that all planned analyses were carried out or how deviations were handled. Since numerical efficacy results and analyses are not reported in the registry record, multiplicity and missing-data considerations cannot be evaluated against actual estimates. These gaps limit the ability to judge the robustness and precision of any efficacy conclusion.
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 |
|---|---|---|---|
| BMN 270 4E13 vg/kg | 0 | 1 | 0.0% |
| Total | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| BMN 270 4E13 vg/kg | 0 of 1 |
| Total | 0 of 1 |
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 |
|---|---|
| BMN 270 4E13 vg/kg | 1 of 1 |
| Total | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BMN 270 4E13 vg/kg | Total |
|---|---|---|---|
| Pyrexia | General disorders | 1 of 1 | 1 of 1 |
| Hepatocellular injury | Hepatobiliary disorders | 1 of 1 | 1 of 1 |
| Nasopharyngitis | Infections and infestations | 1 of 1 | 1 of 1 |
| Alanine aminotransferase increased | Investigations | 1 of 1 | 1 of 1 |
| Myalgia | Musculoskeletal and connective tissue disorders | 1 of 1 | 1 of 1 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 1 of 1 | 1 of 1 |
The adverse-event information separates serious events, other adverse events, and deaths for the treatment group, and also gives a total row. For BMN 270 4E13 vg/kg, the registry record lists 1 at risk for serious adverse events and 0 affected. For other adverse events, it lists 1 at risk and 1 affected. Deaths are listed as 0. The total row repeats those same counts; it should not be added to the treatment-group row.
In general, “at risk” is the denominator used to interpret the reported affected count for that category. With enrollment of 1, these safety figures describe a very limited observation base and do not characterize the range of possible adverse events in a larger group. The record lists no top serious adverse-event terms. That is not the same as evidence that no safety concerns could occur; it only describes the entries recorded for this study.
The registry record does not provide further details about event definitions, severity, timing, relatedness to treatment, duration, or follow-up completeness. Nor does it provide a broader comparative safety assessment, since the design has no concurrent control group. These counts can be read as the adverse-event entries reported in the registry, but they do not establish a comparative risk or a complete safety profile.
12. What the Result Does, and Does Not, Mean
The record establishes that a Phase 3, open-label, single-arm study evaluated a single administration of valoctocogene roxaparvovec at 4E13 vg/kg in Hemophilia A patients described as having residual Factor VIII levels ≤1IU/dL and receiving prophylactic Factor VIII infusions. It specifies Factor VIII activity at Week 52 as the primary outcome and identifies changes in annualized Factor VIII use and bleeding episodes as secondary outcomes. It also gives limited adverse-event counts.
Those design and outcome details do not show the size of an observed efficacy change. The registry record does not report a numerical primary endpoint result or numerical results for the secondary outcomes. It also does not report confidence intervals or other estimates of uncertainty. Accordingly, the effect magnitude and its precision cannot be assessed from this record. The planned outcome definitions should not be interpreted as evidence that an outcome improved or worsened.
The single-arm design does not provide a concurrent control comparison. Even if before-and-after measurements were available, changes within the treated group alone would not directly identify what would have occurred under an alternative treatment or no treatment. The record's enrollment of 1 further limits how much can be learned about variation across people. It cannot establish how representative an individual observation would be of a wider population.
The endpoint title's reference to a median and the analysis description's reference to a mean with standard deviation are not reconciled in the registry record. That ambiguity, together with the absence of numerical results, prevents assessment of the endpoint summary itself. The safety counts are also descriptive and based on the limited group recorded; they are not a comparison of safety between treatments.
Thus, the record is useful for understanding the study's intervention, design, endpoint definitions, and recorded adverse-event counts. It does not establish treatment efficacy, comparative benefit, or a complete safety profile. A completed study status is not a substitute for results reporting, and a planning illustration is not observed evidence or observed power.
13. Why This Trial Matters Statistically
This study illustrates why design and reporting details are essential to interpreting clinical trial statistics. A Phase 3 label does not by itself indicate that a study is randomized or controlled. Here, the registry record identifies a single-group, open-label design with allocation listed as not applicable and masking as none. Those features determine what comparisons the design can support: it describes outcomes within a treated group rather than a randomized contrast against a control group.
The record also makes the distinction between an endpoint definition and an endpoint result especially important. It identifies Factor VIII activity at Week 52 as the primary focus and gives the assay, unit, and analysis population, but does not report a numerical result or uncertainty estimate. Without those quantities, readers cannot assess effect size or precision. The differing references to a median and to a mean with standard deviation further show why consistent statistical terminology matters.
Enrollment of 1 and the small set of recorded adverse-event counts also highlight the limits of descriptive evidence from a very limited observation base. The safety entries can be read as registry counts, but cannot characterize the full range of possible events or provide a comparative risk estimate. In general, inferential claims require attention to both the design and the amount and quality of reported information.
Finally, planning illustrations and trial results answer different questions. Planning calculations depend on assumptions about effect, allocation, and statistical methods; they are not observed outcomes, and they do not show achieved power. The registry record says the planning illustration is not the trial's own design. This distinction helps prevent hypothetical sample-size calculations from being mistaken for evidence about what the study found.
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 main trial-specific limitation is the single-arm design. There is no concurrent control group, and the record lists allocation as not applicable and masking as none. As a result, the design does not support a randomized comparison, and within-group changes cannot be interpreted as a direct estimate of the difference between treatment and control. This limitation remains even if outcome values are later reported.
Enrollment is recorded as 1, limiting the descriptive scope of the study. A result from such a limited enrollment cannot establish how responses vary among a broader group. The registry record does not provide participant-level baseline characteristics or a numerical primary endpoint result, so it is not possible to assess the observed response or its representativeness from this record.
The primary endpoint description also has an unresolved summary-statistic inconsistency: its title refers to a median, while the analysis description identifies a mean and standard deviation. The record does not clarify which summary is intended or report its value. It gives no numerical efficacy results, uncertainty estimates, or detailed outcome-analysis methods. Missing-data handling, multiplicity procedures, and the statistical analysis plan are not reported in the registry record.
For safety, the record provides only counts, with no additional details about timing, severity, relatedness, event definitions, or completeness of follow-up. The total row duplicates the treatment-group counts and should not be treated as another group. These limitations mean the record can describe the study framework and its recorded safety entries, but cannot support a precise assessment of efficacy or comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients at a Dose of 4E13 vg/kg — NCT03392974.
- Registry record last updated 2023-10-03; status last verified 2023-09.
- Results first posted 2021-10-08.
- 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 NCT03392974, a completed Phase 3, open-label, single-arm study sponsored by BioMarin Pharmaceutical. It evaluated a single administration of valoctocogene roxaparvovec at 4E13 vg/kg in Hemophilia A patients described as having residual Factor VIII levels ≤1IU/dL and receiving prophylactic Factor VIII infusions. Enrollment is recorded as 1.
The primary outcome concerns change in Factor VIII activity at Week 52, measured by chromogenic substrate assay, with intention-to-treat identified as the analysis population. Secondary outcomes concern annualized exogenous Factor VIII use and bleeding episodes requiring replacement treatment. The registry record does not report numerical efficacy results or detailed analysis methods, and it does not reconcile the endpoint title's reference to a median with the mean and standard deviation listed in the analysis description.
Serious adverse events affected 0 of 1 at risk; other adverse events affected 1 of 1 at risk; deaths were 0. These counts are descriptive and do not provide a comparative safety estimate. The record offers design and outcome definitions, but not the numerical efficacy evidence needed to evaluate effect magnitude or precision.