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 A Study of the Safety and Immunogenicity of Repeated rhC1INH Administration (NCT00851409), a na phase 2 study. The primary outcome is HAE Attacks/Week.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00851409 |
| Phase | Phase 2 |
| Condition | Genetic Disorders, Hereditary Angioedema |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 25 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pharming Technologies B.V. |
| Results posted | Yes |
2. Clinical Question
The study asked whether weekly administration of recombinant human C1 inhibitor (rhC1INH) could be evaluated for safety and a prophylactic effect in patients with hereditary C1 inhibitor deficiency, described in the registry as hereditary angioedema (HAE). It was an exploratory study, not a randomized comparison against a concurrent control group. The primary outcome was HAE attacks per week, assessed in two periods: a historical period before treatment and an eight-week treatment period.
Population
Patients enrolled with hereditary C1 inhibitor deficiency, identified in the record as HAE. The registry lists an enrollment of 25. Further eligibility details and a fuller description of the analyzed population are not reported in the registry record.
Intervention
Weekly administration of 50 IU/kg recombinant human C1 inhibitor. The registry describes administration by slow IV injection over 4 to 5 minutes during an eight-week period.
Comparator
The primary outcome description contrasts the treatment-period attack rate with a historical rate derived from patients’ reports of attacks during the past 2 years. There was no randomized concurrent comparator group.
Primary question
How did the mean HAE attacks per week during the prophylaxis period compare descriptively with the historical attacks per week, and what safety experience was recorded during repeated administration?
The registry record does not report numerical means or confidence limits for the attack-rate outcome. Consequently, the size and precision of any historical-to-treatment contrast cannot be described from the posted results. The question is therefore best understood as an exploratory assessment of a before-and-during-treatment pattern, alongside safety reporting, rather than as a controlled estimate of treatment effect.
3. Trial Design
This was an open-label exploratory Phase II study with a single-group model. The registry lists allocation as not applicable and masking as none. All participants were assigned to the listed intervention: weekly administration of 50 IU/kg recombinant human C1 inhibitor. The registry lists an enrollment of 25 and a completed status. The study start is recorded as 2009-06, with primary completion in 2010-03.
The design did not include random assignment or a concurrent control group. Instead, the primary outcome description uses a historical attack rate, based on patients’ reports of HAE attacks during the past 2 years, and compares it with an attack rate during an eight-week treatment period. Patients received the weekly dose by slow IV injection over 4 to 5 minutes. This structure allows description of a change across periods for the enrolled group, but it cannot separate a treatment-related change from other differences between the historical and treatment periods.
The trial’s open-label status means treatment was not masked. The registry does not report a blinding procedure, a protocol for collecting the historical attack reports, or details on how the analysis handled variation in the amount or reliability of those reports. It also does not report a formal statistical analysis plan, a sample-size justification, or interim analyses. These omissions limit assessment of how the study planned to address measurement, selection, or analysis decisions.
A secondary outcome is identified as pharmacokinetic/pharmacodynamic parameters. The record lists two outcome measures, but numerical outcome results for the primary attack-rate measure are not reported in the registry record. The study is therefore described by its planned structure and the available safety counts; the record does not support a numerical conclusion about the primary endpoint.
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 | Recombinant Human C1 Inhibitor |
|---|---|
| STARTED | 25 |
| COMPLETED | 25 |
| 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 | Recombinant Human C1 Inhibitor |
|---|---|---|
| Participants analysed | 25 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 25 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 20 |
| Sex: Female, Male: Male | Participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as HAE Attacks/Week, measured over 8 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | attacks/week |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is HAE attacks per week. It is a continuous summary of an event rate: patients were asked about the number of attacks during the past 2 years, which was converted to attacks per week and labeled historical. Attacks during the eight-week treatment period were also expressed as attacks per week and labeled prophylaxis. The registry specifies a mean and a 95% confidence interval as the endpoint summary.
An attack rate is used to place periods of different duration on a common time scale. The mean can describe the average rate across the analyzed group, while a confidence interval conveys uncertainty around that estimated mean. In general, a confidence interval is not a guarantee that an individual patient’s rate falls within its limits; it describes uncertainty about a group-level estimate under the analysis assumptions.
The historical rate offers a reference for describing attack frequency before treatment, but it is not a concurrent control. The two periods also differ in how the information was obtained: the historical value was recalled for the past 2 years, whereas the prophylaxis value was recorded during an eight-week treatment period. Recall, changes over time, and the shorter observation period may affect the comparability of the rates.
Although the outcome description specifies a mean and 95% confidence interval, their numerical values are not reported in the registry record. The posted record therefore does not permit assessment of the observed attack-rate means, the estimated contrast, or its precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes an exploratory, open-label study in which the primary outcome was HAE attacks per week during an eight-week period of weekly rhC1INH, considered against a historical attack rate based on reports covering the past 2 years. This design can frame a descriptive question about attack rates across periods, but it does not provide a randomized comparison with a concurrent control group. Any apparent difference between periods would therefore need to be interpreted cautiously, particularly because the historical value depends on recall and the periods are not equivalent in duration or method of ascertainment.
The key quantitative information needed to judge the primary endpoint is absent from the posted record: numerical means, confidence intervals, and a numerical comparison between historical and treatment-period rates are not reported in the registry record. Without those values, neither the magnitude of the observed pattern nor its statistical precision can be characterized. The stated endpoint type and confidence-interval format alone do not reveal the direction or size of a result.
The registry lists an enrollment of 25. That enrollment figure is not a substitute for the number analyzed for the primary endpoint; an analysis population and missing outcome data are not reported in the registry record. The record also does not describe whether the attack-rate analysis adjusted for baseline rate, accounted for repeated observations, or used any particular model. Thus, the statistical basis for a primary-outcome estimate cannot be evaluated from the record.
Safety information is more concrete but remains limited. The registry lists 25 at risk in the intervention group and 2 affected in the serious adverse event category; it also lists 25 at risk and 2 affected in the other adverse event category. Appendicitis and laryngeal edema are each listed among the top serious terms at 4.0%. Deaths are not reported in the registry record. These counts describe what the record reports; they do not, by themselves, establish whether an event was caused by treatment or how the risk compares with another treatment or with no treatment.
Overall, the posted information supports a description of the study’s design and the reported safety counts, but not a numerical interpretation of the primary attack-rate outcome. This is an important distinction: a trial can specify an outcome and its intended summary while still lacking posted numerical results needed to judge the observed estimate and uncertainty. No claim about the prophylactic effect can be made from the available primary-outcome information.
9. Statistical Methods Explained
The registry identifies the primary outcome as a continuous measure summarized by a mean and a 95% confidence interval. The outcome is an attack rate, expressed as attacks per week, for a historical period and an eight-week prophylaxis period. Numerical results for those summaries are not reported in the registry record. The following explains the statistical ideas relevant to interpreting this kind of outcome, without asserting that a particular analysis was used.
What does the mean describe?
A mean combines individual observations into a group-level average. For an attack-rate outcome, it can describe average attacks per week in the analyzed group during the specified period. It does not show the range of individual experiences or whether the average represents every participant well. When a measure is based on counts, individual rates may vary substantially, and a group mean can conceal that variation.
The registry’s outcome description gives rates for a historical period and for prophylaxis. A comparison of these means would be a useful descriptive summary if both estimates and their uncertainty were available. However, the registry record does not report the numerical means or a numerical estimate of their difference. It is not possible to infer either from the endpoint definition.
What does a confidence interval convey?
A confidence interval describes uncertainty about an estimated quantity under the assumptions of the method used to calculate it. A narrower interval indicates greater precision for that estimate than a wider interval, while neither interval width nor inclusion of a particular value proves that an effect is present or absent. Confidence intervals are not individual-level ranges and should not be read as the likely range of outcomes for each patient.
The endpoint description specifies a 95% confidence interval, but the numerical limits are not reported in the registry record. Without the interval, readers cannot assess the precision of the mean. Without the means for the two periods, readers also cannot judge the direction or scale of the descriptive contrast. A confidence level alone is not a result.
Why does the historical comparison matter?
A historical comparison uses measurements from before the treatment period rather than observations from a concurrent control group. In this study, the historical attack rate was calculated from patient reports about attacks during the past 2 years. The prophylaxis rate was based on attacks during the eight-week treatment period. Recalling a longer past period can introduce errors in memory or reporting, while observation during treatment occurs over a defined, shorter period.
Even when the same enrolled patients contribute information for both periods, this design does not make the periods interchangeable. Attack frequency may vary over time for reasons unrelated to treatment, and measurement conditions differ. A randomized concurrent group can help address some time-related explanations, whereas a historical reference cannot rule them out. The record does not report an analysis that adjusts for these limitations.
Why can count outcomes be statistically challenging?
Attack rates arise from event counts over time. In general, count data may show more variability than a simple statistical model expects, a property often called over-dispersion. When over-dispersion is present but not accommodated, uncertainty estimates can be too small. Conversely, a model that allows extra variation can produce more appropriate uncertainty when its assumptions fit the data. The registry record does not identify a count model, describe a check for over-dispersion, or report the underlying event-count distribution, so it is not possible to determine how this issue was handled.
Rates also depend on the time each person is observed and on how events are collected. A common time unit helps express periods on a comparable scale, but it does not eliminate differences in recall, observation, or exposure time. The record does not report participant-level follow-up detail or missing-data handling for the primary outcome.
What can the design support?
With a single group and a historical reference, the design can describe experience during the treatment period and compare it descriptively with a pre-treatment rate if the numerical outcome data are available. It cannot, on its own, establish that a change was caused by treatment. Open-label assessment can also influence reporting or assessment, although the record does not describe whether or how that occurred.
The registry lists no analysis entries. A detailed statistical plan, including the method used for the primary estimate, handling of repeated measurements, treatment of missing observations, and any adjustment strategy, is not reported in the registry record. Therefore, readers should distinguish the endpoint’s stated summary format from a fully documented analysis. The study’s exploratory designation is consistent with treating its design and posted results as descriptive, but does not supply missing numerical estimates.
Planning illustrations, when based on an observed effect, are not observed power. The planning assumptions listed for such illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. Those assumptions describe a planning exercise, not this single-group study’s design or its analysis. No numerical planning result or observed primary effect is reported in the registry record, so no planning figure can fill the gap in the endpoint results.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies the primary outcome as HAE attacks per week and lists pharmacokinetic/pharmacodynamic parameters as a secondary outcome. It also lists two outcome measures. The record does not report a multiplicity strategy, such as a prespecified hierarchy or adjustment across outcomes. Without such information, readers cannot determine how the study intended to control the chance of a misleading finding when considering more than one outcome or analysis.
The registry does not report numerical primary-outcome estimates, and it does not list analysis entries. The analysis population for the attack-rate outcome, the number of participants with usable measurements, and the handling of missing outcome observations are not reported in the registry record. There is no basis to assume that all enrolled participants contributed complete data, or to infer how incomplete historical reports or treatment-period observations were treated.
Missing-data methods can affect both an estimate and its uncertainty, especially when missingness is related to outcomes or study participation. General approaches may include defining an analysis population, describing the amount and pattern of missingness, and specifying assumptions for any model or imputation. These details are not reported in the registry record. No interim analyses or sample-size justification are reported either.
Accordingly, the available record does not establish how multiplicity or missingness was addressed. These are reporting gaps, not evidence that a particular method was or was not used outside the registry record.
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 |
|---|---|---|---|
| Recombinant Human C1 Inhibitor | 2 | 25 | 8.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Recombinant Human C1 Inhibitor | 2 of 25 |
Most frequent serious adverse event terms
| Event term | Organ system | Recombinant Human C1 Inhibitor |
|---|---|---|
| Appendicitis | Infections and infestations | 1 of 25 |
| Laryngeal edema | Respiratory, thoracic and mediastinal disorders | 1 of 25 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Recombinant Human C1 Inhibitor |
|---|---|---|
| Anaemia-mild | Blood and lymphatic system disorders | 1 of 25 |
| Anaemia-moderate | Blood and lymphatic system disorders | 1 of 25 |
Serious events with the highest arm-level rate: appendicitis (4.0%), laryngeal edema (4.0%).
The registry lists the intervention group as having 25 at risk for serious adverse events, with 2 affected. It separately lists 25 at risk for other adverse events, with 2 affected. These are category-specific counts as recorded; they should not be added together to infer a number of distinct participants, because the record does not say whether the categories overlap.
Appendicitis and laryngeal edema are each listed as top serious adverse event terms at 4.0%. These percentages should be read as registry-reported figures, not as a comparison of risk against a control group. The record does not provide a concurrent comparator, a causal assessment for these terms, or enough detail to establish their timing or relationship to treatment. The deaths field is null, so deaths are not reported in the registry record.
Serious adverse events and other adverse events are different reporting categories; the counts do not measure the same thing as the primary attack-rate outcome. They also do not describe all aspects of safety, such as event duration, severity beyond the serious classification, or outcome after an event. Those details are not reported in the registry record. The safety counts therefore describe the entries available in the registry, rather than providing a complete comparative safety assessment.
12. What the Result Does, and Does Not, Mean
The study record describes an exploratory evaluation of weekly rhC1INH in patients with hereditary C1 inhibitor deficiency. Its primary outcome was the mean HAE attack rate per week, with a historical rate as reference and an eight-week treatment period. The record also lists a secondary pharmacokinetic/pharmacodynamic outcome and reports limited adverse-event counts.
What the record does not establish is the numerical primary result. The historical and prophylaxis means, their 95% confidence intervals, and a numerical contrast are not reported in the registry record. As a result, the posted information cannot show how much the attack rate changed, in which direction it changed, or how precise any estimate was. An endpoint description is not a substitute for those results.
Even if numerical period-specific means were available, this single-group, open-label design would require caution in attributing a difference to treatment. The historical rate relies on retrospective reports and covers a different period from the treatment observation. A concurrent randomized comparison is absent, so changes over time, measurement differences, and other influences could contribute to a before-and-during pattern.
The safety entries report 2 affected among 25 at risk in each of the serious and other adverse event categories. Appendicitis and laryngeal edema are listed at 4.0% each among the top serious terms. These figures do not determine whether events were caused by treatment, and without a control group they do not establish comparative risk. Deaths are not reported in the registry record.
Thus, the available record supports a description of the design and selected safety reporting, but not a conclusion about the magnitude or certainty of the primary attack-rate outcome. It should not be read as proof that treatment does or does not have a prophylactic effect.
13. Why This Trial Matters Statistically
This trial is statistically informative because it makes clear how study design and outcome reporting shape the conclusions that can be drawn. The endpoint is clinically interpretable as attacks per week, and expressing the historical and treatment periods on a common time scale creates a descriptive framework. At the same time, the historical rate comes from recall over the past 2 years, whereas treatment-period events were assessed during eight weeks. That contrast illustrates why consistent measurement and a concurrent comparison matter when interpreting change over time.
The single-group, open-label design is appropriate to recognize as exploratory rather than to treat as a controlled estimate. Without randomization or a concurrent comparator, changes cannot be cleanly separated from time-related or measurement-related influences. Statistical methods cannot fully repair the limitations created by the study structure, particularly when the analysis plan is not reported.
Another important lesson is the distinction between defining an endpoint and reporting its results. The registry specifies a mean and 95% confidence interval, but does not report their numerical values. Readers therefore cannot judge the size of the attack-rate estimates or their precision. This is not merely a technical omission: the estimate and its uncertainty are central to interpreting a continuous primary outcome.
The safety counts also show why denominators and categories need context. The registry gives counts and denominators for serious and other adverse events, but these categories should not be combined to infer distinct affected participants. Nor do the counts, without a comparator and causal information, establish treatment-related risk.
For biostatistical interpretation, the trial underscores the importance of transparent reporting of analysis populations, missing data, model choices, and prespecified analysis methods. Those details, along with numerical endpoint results, are not reported in the registry record. The design and reporting gaps define the limits of what can be concluded from this study record.
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 central limitation for interpreting the primary endpoint is that numerical attack-rate means and 95% confidence intervals are not reported in the registry record. The record consequently does not allow assessment of the observed magnitude, direction, or precision of the primary outcome. The described endpoint and timeframe cannot substitute for the missing estimates.
The historical comparison also has inherent limitations. Historical attacks were derived from patient reports about the past 2 years, while prophylaxis-period attacks were assessed over eight weeks. Recall and reporting may differ between these periods, and the shorter treatment period may capture a different part of a person’s underlying pattern. Because there was no concurrent control group, the design cannot distinguish treatment-associated change from other changes over time.
The study was open-label, so participants and investigators were not masked according to the registry. The record does not report how attacks were verified, how historical reports were collected, or whether outcome assessment followed a standardized procedure. It also does not report the primary-outcome analysis population, missing-data handling, model specification, or treatment of variable follow-up.
The registry lists an enrollment of 25, but the number included in the primary analysis is not reported in the registry record. A formal sample-size justification, interim-analysis plan, and detailed statistical analysis plan are also not reported. The available safety information is limited to category counts and selected serious-event terms; deaths are not reported in the registry record. These limitations do not establish that additional procedures or information did not exist, but they are not documented in the registry record and constrain interpretation of the posted results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of the Safety and Immunogenicity of Repeated rhC1INH Administration — NCT00851409.
- Registry record last updated 2018-06-26; status last verified 2018-04.
- Results first posted 2013-01-31.
- 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 NCT00851409, an open-label exploratory Phase II study of repeated rhC1INH administration in patients with hereditary C1 inhibitor deficiency. It used a single-group design, listed an enrollment of 25, and has a completed status. The recorded study start is 2009-06 and primary completion is 2010-03.
The intervention was weekly 50 IU/kg recombinant human C1 inhibitor, administered by slow IV injection over 4 to 5 minutes during an eight-week period. The primary outcome was HAE attacks per week, comparing a historical rate based on reports about the past 2 years with the rate during prophylaxis. Pharmacokinetic/pharmacodynamic parameters were listed as a secondary outcome.
Numerical primary-outcome means and confidence intervals are not reported in the registry record. The safety listing reports 2 affected among 25 at risk in each of the serious and other adverse event categories; appendicitis and laryngeal edema are each listed at 4.0% among top serious terms. Deaths are not reported in the registry record.