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 Assess Efficacy and Safety of Anti-von Willebrand Factor (vWF) Nanobody in Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP) (NCT01151423), a randomized phase 2 study. The primary outcome is Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01151423 |
| Phase | Phase 2 |
| Condition | Acquired Thrombotic Thrombocytopenic Purpura |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 75 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ablynx, a Sanofi company |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled patients with acquired thrombotic thrombocytopenic purpura (aTTP). The primary endpoint was specified for the ITT population. The registry records an enrollment of 75, but does not report the treatment-group sizes for the primary analysis or the number of participants included in that analysis.
Intervention
Participants assigned to the active-treatment arm received caplacizumab 10 mg once daily as adjunctive therapy to plasma exchange (PE). The study description identifies the investigational treatment as an anti-von Willebrand factor nanobody.
Comparator
The control arm received placebo once daily, also as adjunctive therapy to PE. The trial was randomized, placebo-controlled, and parallel-group. The registry record does not report the allocation ratio or the method used to generate or conceal the allocation sequence.
Primary question
The primary endpoint asks how long it took to achieve a platelet response that was confirmed. Response required a platelet count ≥ 150,000/µL, with confirmation at 48 hours using a new platelet measurement and LDH ≤ 2x ULN. The registry record does not report the numerical comparison between the treatment groups for this endpoint.
3. Trial Design
This was a Phase II, randomized, single-blind, placebo-controlled, parallel-group trial in patients with acquired thrombotic thrombocytopenic purpura. Participants received either caplacizumab or placebo once daily, in both cases as adjunctive treatment to plasma exchange. The caplacizumab arm description specifies 10 mg once daily. The registry records enrollment of 75 and a completed study status.
The primary endpoint was time-to-response, defined as confirmed platelet recovery. The stated timeframe ran from the day of first study-drug administration up to 30 days after first administration. The primary population is identified as the ITT population. The registry record does not report the treatment-group allocation ratio, the random-sequence generation procedure, or allocation concealment. It identifies the study as single-blind but does not report who was blinded or how blinding was maintained.
The registry lists 21 outcome measures, including outcomes related to complete remission, TTP exacerbation and relapse, plasma-exchange use, and resolution of non-focal neurological symptoms. These are outcome categories, not numerical findings. The record does not report results for those secondary outcomes in the registry record for this analysis. It also does not report a numerical primary-endpoint estimate, confidence interval, or hazard ratio. Therefore, the design and endpoint can be described, but the treatment contrast in the primary outcome cannot be quantified from the registry information.
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: 76 subjects were screened, 75 subjects were randomized (= Intent-to-treat \[ITT\] population): 36 in the ALX-0081 group, 39 in the placebo group.
Overall Study
| Stage | Caplacizumab | Placebo |
|---|---|---|
| STARTED | 36 | 39 |
| Received Study Drug | 35 | 37 |
| COMPLETED | 20 | 21 |
| NOT COMPLETED | 16 | 18 |
Reasons for not completing this period:
| Reason | Caplacizumab | Placebo |
|---|---|---|
| Study terminated by Sponsor | 9 | 10 |
| Protocol Violation | 0 | 1 |
| Physician Decision | 1 | 1 |
| Pregnancy | 0 | 1 |
| Death | 0 | 1 |
| Adverse Event | 3 | 0 |
| Withdrawal by Subject | 1 | 3 |
| Lost to Follow-up | 1 | 0 |
| Diagnosed as non-TTP patient | 0 | 1 |
| Participated in other clinical trial | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: ITT Population
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 | Caplacizumab | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 36 | 39 | 75 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 35 | 38 | 73 |
| Age, Categorical: >=65 years | Participants | 1 | 1 | 2 |
| Age, Continuous | years | 40.6 (SD 12.7) | 42.5 (SD 13.18) | 41.6 (SD 12.9) |
| Sex: Female, Male: Female | Participants | 24 | 20 | 44 |
| Sex: Female, Male: Male | Participants | 12 | 19 | 31 |
| Race/Ethnicity, Customized: Race/Ethnicity – Caucasian | Participants | 32 | 34 | 66 |
| Race/Ethnicity, Customized: Race/Ethnicity – Black | Participants | 4 | 5 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL, measured over From the day of first study drug administration up to 30 days after first study drug administration.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint measures time from the first study-drug administration to confirmed platelet response, within the stated timeframe of up to 30 days after first administration. A response required platelet recovery to ≥ 150,000/µL. Confirmation was required at 48 hours: a new platelet measurement had to remain ≥ 150,000/µL, and lactate dehydrogenase (LDH) had to be ≤ 2x the upper limit of normal (ULN). The primary population is identified as the ITT population.
Time to response captures how quickly a defined event occurs, rather than only whether a participant ever reaches the event threshold. Requiring confirmation helps distinguish a sustained response from a single qualifying measurement. These are general features of time-to-event endpoints and confirmation rules; they do not establish that the endpoint was achieved more often or sooner in either arm.
The registry identifies the endpoint summary measure as a median with a 95% confidence interval. A median time describes the midpoint of the observed time distribution under the analysis used; a confidence interval conveys uncertainty around that estimate. The numerical median and interval for each arm, and the statistical comparison between arms, are not reported in the registry record. The endpoint definition is available, but its estimated treatment effect and precision cannot be assessed from the reported details.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The trial’s primary question concerns time to confirmed platelet response among patients with aTTP receiving caplacizumab or placebo alongside plasma exchange. The registry defines the response and identifies the ITT population, but the numerical primary-endpoint result is not reported in the registry record. Consequently, the direction, size, and precision of the treatment contrast cannot be described. No conclusion about the relative timing of response between arms follows from the endpoint definition alone.
The record identifies the primary summary as a median and 95% confidence interval. Those statistics would help characterize the observed time to response and uncertainty in the estimate. However, the arm-specific medians, their confidence intervals, and a comparative estimate are not available in the registry record. There is therefore no basis to judge whether any observed difference was large or small, or how compatible the data were with different possible effects.
The registry also states that the primary outcome has several categories or time points and was not reduced to one comparison. This makes a single headline contrast especially difficult to interpret from the available record: the definitions and analysis choices for those categories or time points are not reported. The registry entries identify one analysis, but do not describe its model, handling of censoring, or inferential procedure. The registry record also does not report a numerical hazard ratio. No treatment effect should be inferred from the study title, planned endpoint, or the presence of outcome measures.
General statistical context: randomization is intended to support a fair comparison by assigning treatment independently of participant characteristics, while blinding can reduce some forms of bias in treatment delivery or outcome assessment. The registry identifies the trial as randomized and single-blind, but does not describe sequence generation, concealment, or who was blinded. These design labels alone do not establish that all potential sources of bias were controlled.
The enrollment figure is not a substitute for the number analyzed for the primary endpoint. Group-specific analysis counts and the handling of participants with missing endpoint data are not reported in the registry record. These omissions limit assessment of the analysis population and the precision of any result. The outcome definitions and design can be understood, but the registry entries do not support a numerical efficacy interpretation.
9. Statistical Methods Explained
The registry describes a time-to-event primary endpoint summarized by a median and 95% confidence interval. It also indicates that only sponsor-reported hazard ratios are used for time-to-event summaries. Numerical primary-endpoint estimates and hazard ratios are not reported in the registry record. The statistical concepts below are general explanations, not claims about unreported analyses from this trial.
What does time to response measure?
A time-to-event outcome records the time until a defined event, such as confirmed platelet response. The event definition matters: in this trial, a platelet count ≥ 150,000/µL had to be confirmed at 48 hours, with a new qualifying platelet measurement and LDH ≤ 2x ULN. The stated observation window began on the day of first study-drug administration and extended up to 30 days after that administration. A time-to-event analysis can use information about when events occur, rather than reducing the outcome to a simple yes-or-no status at a single time point.
In general, some participants may not experience the event during the observation period or may not have complete follow-up. Such observations are often treated as censored in time-to-event methods. The registry record does not report how censoring was handled, whether any participants were censored, or the analysis assumptions used for the primary endpoint. These details matter because the interpretation of time-to-event estimates depends on how observed follow-up is incorporated.
What does a median and confidence interval mean?
In general, the median time is the point at which half of the estimated time distribution lies on each side, subject to the specific estimator and data. It is not an average time and does not describe every participant’s experience. A 95% confidence interval expresses uncertainty in an estimated quantity under the statistical method used; it is not a range containing 95% of individual response times. The registry identifies a median and 95% confidence interval as the primary endpoint summary, but does not report their numerical values for the treatment groups.
What does a hazard ratio mean?
In general, a hazard ratio compares the instantaneous event rates between groups over follow-up, conditional on the model and its assumptions. It is not the same as a ratio of median times and does not directly state the probability that a particular participant will respond. The trial details indicate that sponsor-reported hazard ratios are the basis for time-to-event summaries, but no numerical hazard ratio is reported. The registry record does not describe the model specification or diagnostics, so those aspects cannot be evaluated.
How should planning calculations be read?
General sample-size illustrations are planning exercises, not observed trial outcomes and not estimates of the probability that this completed trial found an effect. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event illustrations, the stated method uses the total number of events and the Schoenfeld approach. These assumptions describe the illustrations, not the trial’s original design. The registry record does not report the original sample-size justification or indicate that these illustration assumptions governed the trial.
The observed effect needed to produce numerical planning illustrations is not included in the registry record, nor are the resulting illustration values. Thus no specific planning requirement can be stated. In general, a planning calculation depends on its assumed effect, significance level, allocation, and method; changing those assumptions changes the estimated requirement. Such a calculation should not be described as observed power, which is not a useful replacement for examining an effect estimate and its uncertainty.
What can be inferred from randomization and blinding?
Randomization is a design method intended to make treatment groups comparable on average with respect to measured and unmeasured baseline characteristics. A parallel-group design assigns participants to one study arm rather than exposing each participant to both study treatments. Blinding is intended to limit influences of treatment knowledge on care, reporting, or assessment. These are general principles. The registry labels the study randomized, parallel, and single-blind, but the method of randomization and the identity of the blinded parties are not reported in the registry record. The labels alone do not establish how successfully these protections were implemented.
The registry identifies the primary population as ITT. In general, an ITT analysis aims to analyze participants according to their randomized assignment, preserving the comparison created by randomization. The record does not give the number analyzed in each arm, explain how missing endpoint data were handled, or describe deviations from assigned treatment. Therefore, the ITT label is informative about the intended analysis population, but it is not enough to reconstruct the analysis or assess its completeness.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 21 outcome measures and states that the primary outcome has several categories or time points and was not reduced to one comparison. Multiple outcomes or comparisons can raise a multiplicity concern: when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. This is a general statistical consideration, not evidence that a particular adjustment was or was not used in this trial.
The multiplicity strategy, if any, is not reported in the registry record. The record does not identify a hierarchy of outcomes, a family of tests, an adjustment procedure, or a prespecified rule for interpreting multiple time points or categories. As a result, the intended confirmatory status of any individual comparison cannot be assessed from these registry entries. The number of listed outcomes by itself does not establish how many statistical tests were conducted.
The primary population is identified as ITT, but the number analyzed by arm and the handling of missing or incomplete primary-endpoint observations are not reported in the registry record. There is no reported description of imputation, censoring rules, withdrawal handling, or sensitivity analyses for missing data. These omissions prevent assessment of whether missingness could have influenced the estimated time to response.
The registry reports one analysis, but does not describe the statistical plan or analysis model. The original sample-size justification, interim analyses, and analysis timing are not reported in the registry record. These details should not be inferred from the trial phase, enrollment, or endpoint type.
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 |
|---|---|---|---|
| Caplacizumab | 20 | 35 | 57.1% |
| Placebo | 19 | 37 | 51.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Caplacizumab | 0 of 35 |
| Placebo | 2 of 37 |
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 |
|---|---|
| Caplacizumab | 33 of 35 |
| Placebo | 37 of 37 |
Most frequent serious adverse event terms
| Event term | Organ system | Caplacizumab | Placebo |
|---|---|---|---|
| Thrombotic thrombocytopenic purpura | Blood and lymphatic system disorders | 13 of 35 | 13 of 37 |
| Dizziness | Nervous system disorders | 2 of 35 | 0 of 37 |
| Headache | Nervous system disorders | 1 of 35 | 1 of 37 |
| Transient ischemic attack | Nervous system disorders | 1 of 35 | 1 of 37 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 1 of 35 | 1 of 37 |
| Anemia | Blood and lymphatic system disorders | 1 of 35 | 0 of 37 |
| Atrial fibrillation | Cardiac disorders | 0 of 35 | 1 of 37 |
| Atrial flutter | Cardiac disorders | 0 of 35 | 1 of 37 |
| Retinal hemorrhage | Eye disorders | 1 of 35 | 0 of 37 |
| Abdominal pain | Gastrointestinal disorders | 0 of 35 | 1 of 37 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Caplacizumab | Placebo |
|---|---|---|---|
| Headache | Nervous system disorders | 11 of 35 | 10 of 37 |
| Nausea | Gastrointestinal disorders | 10 of 35 | 10 of 37 |
| Constipation | Gastrointestinal disorders | 7 of 35 | 10 of 37 |
| Hypokalemia | Metabolism and nutrition disorders | 9 of 35 | 8 of 37 |
| Paraesthesia | Nervous system disorders | 7 of 35 | 8 of 37 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 11 of 35 | 4 of 37 |
| Vomiting | Gastrointestinal disorders | 7 of 35 | 7 of 37 |
| Pyrexia | General disorders | 6 of 35 | 6 of 37 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 5 of 35 | 7 of 37 |
| Fatigue | General disorders | 6 of 35 | 5 of 37 |
Serious events with the highest arm-level rate: thrombotic thrombocytopenic purpura (37.1%), dizziness (5.7%), anemia (2.9%), retinal hemorrhage (2.9%), hypertransaminasemia (2.9%).
The registry lists serious adverse-event counts separately for the caplacizumab and placebo groups. For caplacizumab, 20 participants are listed as affected among 35 at risk; for placebo, 19 are listed as affected among 37 at risk. The listed deaths are 0 in the caplacizumab group and 2 in the placebo group. The record also lists other adverse-event counts: 33 among 35 at risk for caplacizumab and 37 among 37 at risk for placebo. These are descriptive counts; they do not establish that treatment caused an event or explain differences between groups.
The most frequent listed serious term is thrombotic thrombocytopenic purpura at 37.1%, followed by dizziness at 5.7%. Anemia, retinal hemorrhage, hypertransaminasemia, and bacterial infection are each listed at 2.9%. The registry entries do not specify the denominator used for these term percentages, so they should not be converted into counts or compared across treatment groups from this information alone.
Safety counts need context, including definitions, exposure, follow-up, and participant characteristics. Those details are not reported in the registry record. The counts and terms describe what is listed, not a causal safety comparison.
12. What the Result Does, and Does Not, Mean
This trial’s registry description establishes the clinical question and the endpoint definition: time to confirmed platelet recovery for patients with aTTP receiving caplacizumab or placebo alongside plasma exchange. It also identifies the trial as Phase II, randomized, single-blind, and parallel-group. These registry entries describe the intended comparison, but do not show its result.
The numerical primary outcome, group-specific medians, confidence intervals, and comparative hazard ratio are not reported in the registry record. Without those estimates, it is not possible to describe the direction or magnitude of the treatment contrast, or how precisely it was estimated. The endpoint definition cannot be used to infer that either group responded sooner. The registry’s note that the primary outcome has several categories or time points also means that the primary comparison is not represented by a single reported contrast in the registry record.
The safety figures are descriptive. They identify counts of participants affected and listed deaths, along with serious-event terms and percentages. They do not by themselves establish causation or provide a complete comparison of safety over time. The denominator for the listed term percentages is not reported in the registry record.
General statistical interpretation depends on more than whether a result is described as statistically significant. Effect size, uncertainty, outcome definition, missing data, and analysis choices all matter. Here, the lack of numerical efficacy estimates prevents that assessment. The registry entries support a description of the study design, endpoint, and selected safety listings, but not a conclusion about the comparative efficacy or overall safety of the study treatments.
13. Why This Trial Matters Statistically
The trial illustrates why endpoint definitions are central to interpreting clinical research. A platelet response was not defined by a single threshold measurement alone: the registry required confirmation at 48 hours, a new qualifying platelet measurement, and LDH ≤ 2x ULN. Those conditions clarify what counted as the event for the time-to-response endpoint.
It also highlights the distinction between an endpoint’s definition and its result. A registry may specify the population, timeframe, and summary measure without reporting the estimates needed to judge the treatment contrast. In this record, the primary measure is identified as a median with a 95% confidence interval, but the numerical result is not reported in the registry record. Statistical interpretation therefore has to stop short of claims about the direction, size, or precision of an effect.
The registry notes several categories or time points for the primary outcome and lists multiple other outcomes. This makes transparent reporting of the analysis strategy important: readers need to know which comparisons were planned, how multiple tests were handled, and how incomplete follow-up was addressed. Those details are not reported in the registry record.
Finally, the study labels—randomized and single-blind—describe design intentions, but the record does not report enough detail to evaluate sequence generation, concealment, or who was blinded. The trial is a useful example of how design features, outcome definitions, numerical results, and analysis methods each contribute distinct information. No one element can substitute for the others.
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 limitation for interpreting efficacy from the registry entries is the absence of numerical primary-endpoint results. The record identifies the median and 95% confidence interval as the summary measure but does not report arm-specific estimates or a comparative estimate. The primary outcome is also described as having several categories or time points without a single reported comparison. Its full analysis structure is therefore unclear.
The record identifies the primary population as ITT but does not report the number analyzed by arm, missing-data procedures, censoring rules, or sensitivity analyses. The enrollment figure of 75 does not establish the number contributing to the primary analysis. The method used to generate or conceal random allocation, the identity of the blinded parties, and the original sample-size justification are not reported in the registry record.
The registry lists safety counts and serious-event terms, but the denominator for the term percentages is not reported. The registry entries also do not describe exposure duration or how adverse events were collected and classified. Consequently, these listings cannot provide a complete assessment of comparative safety.
The record lists secondary outcomes, but their numerical results are not included in the registry record for this analysis. The statistical plan, multiplicity approach, and any interim analyses are also not reported. These limitations constrain interpretation; they do not show that a particular method was absent or that a particular bias occurred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Assess Efficacy and Safety of Anti-von Willebrand Factor (vWF) Nanobody in Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP) — NCT01151423.
- Registry record last updated 2023-04-04; status last verified 2019-05.
- Results first posted 2019-05-29.
- 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 a completed Phase II, randomized, single-blind, placebo-controlled, parallel-group study of caplacizumab as adjunctive treatment to plasma exchange in patients with aTTP. The caplacizumab arm is described as 10 mg once daily, and the comparator received placebo once daily. Enrollment is recorded as 75.
The primary endpoint was time to confirmed platelet response, defined using platelet recovery ≥ 150,000/µL and confirmation at 48 hours with LDH ≤ 2x ULN. The primary population is identified as ITT, and the stated timeframe extends up to 30 days after first study-drug administration. The registry identifies a median and 95% confidence interval as the summary measure, but the numerical primary result is not reported in the registry record.
Safety listings include serious-event counts, deaths, and serious-event terms. The registry also lists 21 outcome measures. Numerical results for secondary outcomes, detailed analysis methods, and missing-data procedures are not reported in the registry record.