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 Investigate the Long-term Efficacy and Safety of Human-cl rhFVIII in Previously Treated Patients (PTPs) (NCT01341912), a na phase 3 study. The primary outcome is Long-term Immunogenicity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01341912 |
| Phase | Phase 3 |
| Condition | Severe Hemophilia A |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Octapharma |
| Results posted | Yes |
2. Clinical Question
Population
Previously treated patients with severe haemophilia A. The registry record lists an enrollment of 3 participants.
Intervention
Human-cl rhFVIII, described as recombinant FVIII derived from a human cell line.
Comparator
No comparator group is described. This is a single-group study, and allocation is listed as not applicable.
Primary question
How many participants experienced FVIII inhibitors during long-term monitoring, planned for up to 3 years?
The registry describes a phase 3 extension study in previously treated patients with severe haemophilia A. Its stated purpose was to study long-term efficacy, safety and tolerability of Human-cl rhFVIII. The primary outcome concerns long-term immunogenicity, expressed as the occurrence of inhibitors against FVIII. The outcome description says participants were to be monitored every 3 months, with blood samples assessed for inhibitor activity using the modified Bethesda assay, Nijmegen modification, in a central laboratory.
The study also lists a secondary aim concerning efficacy in treatment of bleeding episodes and surgical prophylaxis. The information available does not report the results of that efficacy aim. Nor does it report a primary outcome count for inhibitor occurrences. The central question can therefore be described from the study objective, but the posted information does not establish the observed frequency of inhibitors or quantify efficacy.
Because the record describes no control group, it cannot provide a like-for-like comparison between Human-cl rhFVIII and another treatment or a control condition. The registry record does not report a comparative causal estimate. The appropriate interpretation is therefore limited to the study's stated questions and the outcomes actually posted.
3. Trial Design
This is a completed phase 3 extension study with a single-group model. The registry lists 3 enrolled participants and identifies Human-cl rhFVIII as the intervention. Allocation is listed as not applicable, and masking is listed as none. These design features mean the record does not describe random assignment or blinded assessment, and it does not describe a concurrent control arm.
The study title identifies it as an extension to GENA-01. Its official title describes long-term efficacy, safety and immunogenicity in previously treated patients with severe haemophilia A. The stated study purpose is to investigate long-term efficacy, safety and tolerability of Human-cl rhFVIII. The record gives a start date of 2011-06 and a primary completion date of 2012-08; status is completed. The planned primary outcome timeframe is listed as up to 3 years. The record does not explain how that timeframe relates to the listed completion date, so no further inference about follow-up duration is warranted.
The primary outcome is an occurrence count for inhibitors against FVIII. The registry description specifies monitoring every 3 months and central-laboratory measurement using the modified Bethesda assay, Nijmegen modification. A secondary outcome statement concerns long-term efficacy in treating bleeding episodes and in surgical prophylaxis. The record lists 2 outcome measures, but detailed results for those measures are not reported in the registry record.
Enrollment of 3 makes the study a small extension cohort. In a single-group study, descriptions of events can characterize what was recorded among participants, but they do not establish how outcomes would have differed under another treatment. The registry record does not report the protocol rationale for enrollment, a sample-size justification, or additional design details beyond those stated above.
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 | Human-cl rhFVIII |
|---|---|
| STARTED | 3 |
| COMPLETED | 3 |
| NOT COMPLETED | 0 |
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 | Human-cl rhFVIII |
|---|---|---|
| Participants analysed | 3 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 1 |
| Age, Continuous | years | 52 (SD 12.29) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 3 |
| Region of Enrollment: Bulgaria | participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Long-term Immunogenicity, measured over up to 3 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | occurrence of inhibitors |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is long-term immunogenicity, defined in the registry as the occurrence of inhibitors against FVIII. Immunogenicity refers generally to an immune response directed against a treatment. For this study, the outcome is framed as whether inhibitor activity occurred, rather than as a continuous measure of clinical benefit. The registry specifies that blood samples were assessed for inhibitor activity by the modified Bethesda assay, Nijmegen modification, in a central laboratory, with monitoring planned every 3 months for up to 3 years.
Inhibitor occurrence is relevant to a study of an FVIII product because the endpoint addresses an immune response to FVIII. It is distinct from the secondary efficacy aim, which concerns treatment of bleeding episodes and surgical prophylaxis. The endpoint also differs from a broad safety summary: it focuses on a specified immunogenicity outcome rather than all adverse events.
The registry record does not report the observed number of inhibitor occurrences, an assay result distribution, or an estimate of uncertainty for this outcome. It therefore supports a description of what the endpoint was intended to measure, but not a conclusion about the observed frequency or precision of that frequency. The outcome description also does not report a threshold or additional rules for classifying an assay result as an inhibitor occurrence.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a small, single-group extension study and lists 3 enrolled participants. Its primary outcome concerns inhibitor occurrence during monitoring planned for up to 3 years. However, the registry information does not report the primary outcome result. The number of participants with inhibitor occurrences, the number of events, and an uncertainty estimate are not reported in the registry record. Consequently, the endpoint's observed frequency and precision cannot be assessed from the posted information.
The safety summary reports 0 participants affected by serious adverse events among 3 at risk, and 0 participants affected by other adverse events among 3 at risk. These are descriptive registry counts. They do not establish that such events could not occur, and they cannot characterize risks precisely in a cohort of this size. The death count is not reported in the registry record. The listed counts should not be treated as a complete account of event types or timing, since those details are not reported in the information available.
No outcome analyses are listed. The record therefore does not present an inferential comparison, adjusted estimate, confidence interval, or hypothesis test for the primary outcome. A confidence interval, in general, describes the uncertainty around an estimate under a statistical model; without a reported estimate and interval, the precision of the outcome cannot be evaluated. The absence of a reported analysis is not evidence that the outcome had a particular value.
The stated secondary aim concerns long-term efficacy in treatment of bleeding episodes and surgical prophylaxis, but results for that aim are not reported in the registry record. No numerical efficacy estimate should be inferred from the study purpose or the fact that the study is marked completed. The record also provides no control arm for comparison. A single-group cohort can describe recorded outcomes under the study conditions, but cannot by itself show how those outcomes compare with an alternative.
Overall, the posted information describes the design, planned monitoring, and selected safety counts, but offers limited outcome evidence. The serious and other adverse-event counts are zero in the registry summary, while the primary immunogenicity result and efficacy results are not reported. Interpretation should remain at that descriptive level rather than treating missing outcome results as findings.
9. Statistical Methods Explained
The registry presents a single-group study rather than a randomized comparison. Statistical methods should be read in light of that structure: the record can describe outcomes among participants who received Human-cl rhFVIII, but it does not provide a like-for-like control group for estimating a treatment contrast. Allocation is listed as not applicable and masking as none. The registry record does not report a more detailed statistical analysis plan.
What does the primary count represent?
The primary outcome is the occurrence of inhibitors against FVIII, assessed using the modified Bethesda assay with the Nijmegen modification in a central laboratory. The planned monitoring interval is every 3 months, and the timeframe is up to 3 years. A count outcome records occurrences or affected participants, depending on the precise outcome definition and reporting format. The record names the unit as occurrence of inhibitors but does not report the observed result or further rules for handling repeated occurrences. It is therefore not possible to reconstruct a rate, time-to-event estimate, or participant-level pattern from the information available.
In general, counts are discrete outcomes. When counts vary more than expected under a simple statistical model, over-dispersion can matter: a model that assumes too little variability may produce uncertainty estimates that are too narrow. That is a general consideration, not a claim that over-dispersion was present or assessed in this study. The registry record does not report a count model, a dispersion estimate, or an analysis of repeated events.
What does a confidence interval convey?
In general, a confidence interval communicates uncertainty around an estimated quantity under specified assumptions. It helps distinguish a precise estimate from one that is compatible with a wider range of values. The registry information does not report a confidence interval for inhibitor occurrence, the safety counts, or the secondary efficacy aims. With no posted primary outcome estimate, the precision of the main endpoint cannot be evaluated. A small cohort also means that a zero count in a registry summary should not be read as proof that the underlying event risk is zero.
What can a single group establish?
A single-group study can describe what was observed in its participants, subject to how complete and detailed the outcome reporting is. Without a concurrent comparator, it cannot isolate the difference attributable to the intervention from other influences. A before-and-after or historical comparison would require defined data and methods; neither is reported in the registry information. The posted record thus does not support a comparative effect estimate.
The registry lists 0 analyses. This means no outcome analysis is reported in the information available for this record. It does not reveal whether analyses were performed outside the posted record, nor does it justify assuming a particular analysis method. The planned assay and monitoring schedule are reported, but the statistical plan, handling of missing assessments, analysis populations, and methods for uncertainty estimation are not reported in the registry record.
How should planning calculations be read?
General sample-size calculations depend on assumptions about the effect to detect, variability, allocation, and statistical procedure. A planning illustration is not an observed result and is not evidence of the study's original design rationale. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe an illustrative calculation, not the single-group design reported for this study. The registry record does not report the trial's own sample-size justification. Any planning values should not be interpreted as observed power or as evidence that the study was designed around a specific analysis.
For general context, power is a design property that depends on a set of assumptions; it is not a measure of whether a result is true. Calculating an illustration from an observed effect, especially when the relevant outcome estimate is not reported, cannot substitute for a prespecified design justification. The registry record does not provide enough information to evaluate such a justification or establish what assumptions were used when the study was planned.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 2 outcome measures, including the primary immunogenicity outcome and a secondary efficacy aim concerning treatment of bleeding episodes and surgical prophylaxis. The record does not report a multiplicity plan. In general, multiplicity arises when several outcomes or statistical tests are considered: interpreting each test independently can increase the chance of at least one apparently notable result. Statistical plans may address this through prespecified priorities or adjustments, but no such approach is reported in the registry record. No outcome analyses are listed, so there are no posted tests to interpret in light of multiplicity.
Information about missing data is also not reported in the registry record. The outcome description gives a planned monitoring schedule, but does not specify how missed visits, unavailable blood samples, withdrawal, or incomplete follow-up were handled. The record does not report whether outcome data were complete for all enrolled participants. Missingness can affect interpretation because the observed participants or assessments may not fully represent the intended follow-up; without details, that possibility cannot be evaluated for this study.
Analysis populations are not reported in the registry record. It is not stated which participants or assessments were included in any primary or secondary analysis, and no analyses are listed. The registry record also does not report an imputation approach or sensitivity analyses. These omissions limit assessment of how the planned endpoint was translated into an analysis and whether incomplete observations could have affected the reported results.
The absence of these details does not establish that a particular method was or was not used outside the registry record. It means that readers cannot verify the analysis population, missing-data handling, or multiplicity strategy from the posted information.
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 |
|---|---|---|---|
| Human-cl rhFVIII | 0 | 3 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Human-cl rhFVIII | 0 of 3 |
The registry safety summary lists 0 participants affected by serious adverse events among 3 at risk in the Human-cl rhFVIII group. It also lists 0 participants affected by other adverse events among 3 at risk. These are counts of participants affected in the posted summary, not estimates of the probability of an event in a broader population. The death count is not reported in the registry record.
Zero recorded affected participants does not demonstrate that an event is impossible or that the intervention has no safety risks. With only 3 participants at risk, the summary has limited ability to characterize uncommon events, and the registry information does not provide event-level descriptions or timing. The list of top serious adverse event terms is empty in the record, but that does not supply additional detail about safety outcomes beyond the posted counts.
These figures should be read as a concise registry report for this cohort, not as a complete safety profile or a comparison with another treatment. No comparator group is described, and the record does not report a comparative safety analysis.
12. What the Result Does, and Does Not, Mean
The posted record establishes that this completed phase 3 extension study enrolled 3 previously treated patients with severe haemophilia A in a single group receiving Human-cl rhFVIII. It describes a primary immunogenicity outcome based on inhibitor occurrence, with monitoring planned every 3 months for up to 3 years using a specified central-laboratory assay. It also reports zero participants affected by serious adverse events and zero affected by other adverse events in the registry safety summary, each among 3 at risk.
The record does not report the primary outcome result. It therefore does not show how many participants experienced inhibitors, how precisely that outcome was estimated, or what pattern occurred over follow-up. The secondary efficacy aim is described, but results for bleeding episodes or surgical prophylaxis are not reported in the registry record. The registry also lists 0 analyses, so no inferential results are available to assess.
These limits matter because a study objective is not itself a result. Describing the purpose of monitoring does not establish what the monitoring found. Similarly, zero affected participants in the posted safety counts is a descriptive observation for this small cohort; it cannot establish that adverse events do not occur or precisely characterize risk.
The single-group structure also sets a limit on causal interpretation. Without a comparator, the record does not estimate how outcomes would differ under another treatment or condition. It does not provide a randomized treatment contrast. Accordingly, the record supports a description of its design and posted safety counts, but not conclusions about comparative efficacy, comparative safety, or the frequency of inhibitor occurrence.
In general, missing results should remain distinct from negative results. An outcome not reported in the registry record cannot be treated as a finding of no events or no effect. The appropriate conclusion is that the intended primary and secondary questions are described, while the posted results needed to answer them are absent.
13. Why This Trial Matters Statistically
This study illustrates an important distinction between a registered research question and an interpretable result. The record specifies long-term immunogenicity as the primary outcome and describes how inhibitor activity was to be assessed. Yet the result for that endpoint is not reported in the registry record. For statistical interpretation, knowing the measurement plan is useful, but it cannot replace the observed outcome count and its uncertainty.
The design also highlights why study structure matters. A single-group extension cohort can describe observations among enrolled participants, but it does not offer a like-for-like control comparison. The record's status as completed does not resolve that limitation or supply missing outcome analyses. Design labels, planned outcomes, and posted findings answer different questions and should not be conflated.
The safety summary offers another statistical lesson: zero events in a small cohort is a reported count, not proof of zero underlying risk. Interpretation depends on the number at risk, follow-up, event definitions, and reporting completeness. The record gives the at-risk count and affected counts, but does not report event-level detail or the death count.
Finally, the record demonstrates why transparency about analyses matters. It lists no outcome analyses, and it does not report the statistical plan, analysis populations, or missing-data handling. Without those details, readers cannot assess how the planned monitoring was converted into an analysis or how robust any outcome estimate would be. The central statistical contribution of this record is therefore its description of the study question and design, alongside clearly bounded safety counts and substantial gaps in posted outcome 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 interpretation is that the registry record does not report the result for the primary inhibitor outcome. The secondary efficacy aim is also described without results. With no posted outcome analyses, the principal study questions cannot be answered from the information available. No estimate of uncertainty for the primary outcome is reported.
The enrolled cohort contains 3 participants, and the study is single-group, with no comparator described. This restricts the scope of descriptive evidence and does not support a comparative effect estimate. Allocation is listed as not applicable and masking as none. The record does not report a sample-size justification, so the intended precision or design rationale cannot be evaluated.
Details needed to assess outcome completeness are not reported. The registry describes monitoring every 3 months for up to 3 years, but it does not report completed assessment counts, missing-data handling, analysis populations, or sensitivity analyses. The record also does not report the statistical analysis plan or multiplicity handling. These gaps prevent assessment of whether the posted information reflects all planned observations and analyses.
The safety summary is limited to affected-participant counts. It lists 0 serious and 0 other adverse-event-affected participants among 3 at risk, but event-level descriptions and timing are not reported, and the death count is not reported in the registry record. The counts should therefore be interpreted narrowly as the posted summary, not as an exhaustive account of safety or a comparative evaluation.
The record lists a planned primary timeframe of up to 3 years and a primary completion date of 2012-08, but does not explain the relation between those entries. No additional inference about actual follow-up should be drawn from them.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Investigate the Long-term Efficacy and Safety of Human-cl rhFVIII in Previously Treated Patients (PTPs) — NCT01341912.
- Registry record last updated 2020-03-17; status last verified 2020-03.
- Results first posted 2014-02-03.
- 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 describes NCT01341912 as a completed phase 3 extension study of Human-cl rhFVIII in previously treated patients with severe haemophilia A. It is a single-group study with 3 enrolled participants; allocation is not applicable and masking is none. The listed start date is 2011-06, and the primary completion date is 2012-08.
The primary outcome is long-term immunogenicity, defined by occurrence of inhibitors against FVIII, with planned monitoring every 3 months for up to 3 years using a central-laboratory modified Bethesda assay, Nijmegen modification. A secondary aim concerns treatment of bleeding episodes and surgical prophylaxis.
The safety summary lists 0 serious adverse-event-affected participants and 0 other adverse-event-affected participants among 3 at risk. The death count is not reported in the registry record. The primary outcome result, secondary efficacy results, and outcome analyses are not reported. The record therefore describes the study design and intended outcomes, but does not provide the posted results needed to assess the main efficacy or immunogenicity questions.