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 Evaluate the Long-Term Safety and Efficacy of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia (NCT03409744), a na phase 3 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Up to Week 216.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03409744 |
| Phase | Phase 3 |
| Condition | Homozygous Familial Hypercholesterolemia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 116 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Regeneron Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns participants with homozygous familial hypercholesterolemia, including adolescent patients as described in the study objectives. The registry record reports enrollment of 116 participants. It does not report the age distribution, baseline characteristics, or how many participants were adolescents, so those features cannot be used to characterize the enrolled group further.
Intervention
Participants received open-label evinacumab. The study was designed to evaluate long-term safety and tolerability, with lipid parameters and potential development of anti-evinacumab antibodies among the secondary objectives. The registry record does not report treatment schedules or dose details in the information summarized for this study.
Comparator
There was no comparison group: the study is recorded as a single-group study, with allocation not applicable and masking absent. The registry record therefore does not offer a concurrent control group for assessing how outcomes would have differed without evinacumab or under another treatment.
Primary question
The primary endpoint counts participants with treatment-emergent adverse events up to Week 216. The study’s primary objectives focus on long-term safety and tolerability in participants with homozygous familial hypercholesterolemia, including adolescents. The result is descriptive: it records events during treatment but, without a control group, cannot by itself establish whether events were caused by treatment or how event frequency compares with another approach.
3. Trial Design
This is a phase 3, open-label, single-group study of evinacumab in participants with homozygous familial hypercholesterolemia. The registry records no allocation because there is no randomized assignment between treatment groups, and masking is listed as none. Enrollment was 116. The study is marked completed; its recorded start date is 2018-03-13 and its primary completion date is 2023-04-13.
The study summary identifies long-term safety and tolerability as primary objectives, including assessment in adolescent patients. Secondary objectives concern lipid parameters in participants and adolescent participants, and the potential development of anti-evinacumab antibodies. Listed lipid outcomes include changes in LDL-C, Apo B, non-HDL-C and total cholesterol over time. The registry record does not report detailed treatment schedules or the number of participants assessed for each secondary outcome.
Because everyone in the study received open-label treatment and there is no concurrent comparator, the design supports description of observed outcomes during the study, not a controlled estimate of treatment effect. Differences from a hypothetical untreated group, another treatment, or participants’ outcomes at another time cannot be isolated from this design. The registry record does not report a protocol-based sample-size justification, an interim-analysis plan, or a detailed statistical analysis plan. The enrollment figure should therefore be read as the recorded enrollment, not as evidence that a particular statistical precision or power target was achieved.
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: A total of 118 participants were planned to be enrolled. 116 participants were enrolled \& treated. Reasons for screen fail were: 1 participant was unwilling to use protocol defined contraception, and 1 participant had a Low-density lipoprotein cholesterol (LDL-C) level less than the lower limit required for inclusion.
Overall Study
| Stage | Total Evinacumab |
|---|---|
| STARTED | 116 |
| COMPLETED | 106 |
| NOT COMPLETED | 10 |
Reasons for not completing this period:
| Reason | Total Evinacumab |
|---|---|
| Death | 2 |
| Physician Decision | 5 |
| Pregnancy | 1 |
| Lost to Follow-up | 1 |
| Protocol Violation | 1 |
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 | Total Evinacumab |
|---|---|---|
| Participants analysed | 116 | |
| Age, Continuous | Years | 38.8 (SD 15.92) |
| Sex: Female, Male: Female | Participants | 57 |
| Sex: Female, Male: Male | Participants | 59 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 6 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 100 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 10 |
| Race/Ethnicity, Customized: White | Participants | 80 |
| Race/Ethnicity, Customized: Black or African American | Participants | 4 |
| Race/Ethnicity, Customized: Asian | Participants | 12 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 0 |
| Race/Ethnicity, Customized: Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race/Ethnicity, Customized: Not Reported | Participants | 11 |
| Race/Ethnicity, Customized: Other | Participants | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Up to Week 216, measured over Up to 216 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Number of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with treatment-emergent adverse events up to Week 216. It is a count of participants who experienced an event during the specified follow-up period, rather than a measure of how many separate events each participant experienced. The registry defines the safety analysis set as participants who were enrolled and received at least one dose or part of a dose of open-label study treatment.
Counting participants with events is a straightforward way to describe how many people experienced an adverse event during follow-up. It is relevant to a study whose primary objectives concern long-term safety and tolerability. However, a participant count does not by itself convey event severity, duration, recurrence, timing, or whether an event was considered related to treatment. Those features require additional event-level information.
The endpoint’s timeframe is up to 216 weeks, so it describes events recorded across that follow-up window rather than a single visit. The registry record does not report a separate numerical result for this primary endpoint in the information summarized for the study. The adverse-event summary reports counts in serious and other event categories, but those categories should not be treated as a substitute for a separately reported primary-endpoint result unless their relationship is explicitly stated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a single-group study and reports adverse-event counts for the overall group. It records 27 participants in the serious adverse-event category and 79 in the other adverse-event category, with 116 at risk in each category. These are participant counts, not counts of all event episodes. A participant may have experienced more than one event, and the registry summary does not provide the event-level detail needed to describe recurrence or timing.
The listed serious-event terms include Angina pectoris, Angina unstable, Aortic valve disease, Coronary artery disease and Chest pain, each reported as 1.7%, and Acute myocardial infarction, reported as 0.9%. These percentages describe the registry’s listed terms; the record excerpt does not explain the calculation basis or provide enough detail to infer how terms overlap across participants. The record also reports 2 deaths. It does not state in the information summarized whether these deaths were considered treatment-related.
These observations describe events recorded among participants receiving open-label evinacumab. They do not establish that treatment caused the events, nor do they show what event counts would have been under another treatment or without treatment. The absence of a concurrent comparator is important because participants’ health conditions and other factors can also contribute to events. The registry record does not report an adjusted analysis that separates those influences.
The primary endpoint concerns treatment-emergent adverse events up to Week 216, but a separate primary-endpoint count is not reported in the registry record. The reported serious and other event categories are useful descriptive safety information, but they should not be merged or reinterpreted as the primary endpoint without an explicit definition connecting them. Similarly, the lipid outcomes listed as secondary measures do not, in the information summarized, come with numerical results or comparative estimates.
Precision is also difficult to assess from counts alone. The registry record does not report confidence intervals or other uncertainty estimates for these event counts. Such estimates would describe the statistical uncertainty around an observed frequency, but even a precise estimate in a single-group study would not resolve the lack of a control comparison. The results should therefore be read as a record of observed safety events during follow-up, not as a controlled estimate of comparative risk or evidence of a causal treatment effect.
9. Statistical Methods Explained
The principal outcome is a participant count: whether a participant experienced a treatment-emergent adverse event during the specified follow-up period. This is a binary outcome at the participant level, with each person classified according to whether the event occurred. General statistical interpretation of such counts distinguishes the number of participants with an event from the total number of event episodes. One person can contribute to more than one event term or have repeated events, so these measures answer different questions.
For a participant count to be interpreted as a frequency, the denominator and the definition of the analysis population matter. The registry defines the safety analysis set as enrolled participants who received at least one dose or part of a dose of study treatment. The adverse-event summary lists 116 at risk for each of its serious and other categories. The record does not provide additional detail in the information summarized about exclusions, follow-up completeness, or the exact handling of participants who stopped treatment or left follow-up early.
A confidence interval is a general statistical tool for expressing uncertainty around an estimate. It indicates a range of values reasonably compatible with the observed data under the method’s assumptions. A count without an uncertainty interval gives less information about precision, especially when readers want to generalize beyond the participants observed. The registry record does not report confidence intervals for the adverse-event counts. An interval would quantify sampling uncertainty, but it would not address confounding or create a treatment comparison where the design has none.
In a randomized comparative study, an analysis may estimate the difference between groups while accounting for the assigned comparison. This study has a single group, so there is no randomized treatment contrast to estimate. Within-group changes or event counts can be described, but attributing them to evinacumab requires more than observing that they occurred after treatment began. General explanations of causal inference emphasize the need to distinguish treatment effects from other influences, including underlying disease, background care and changes over time. The registry record does not report an analysis designed to make that separation.
Over-dispersion is a general issue that can arise when count outcomes vary more than a simple statistical model expects. It matters when a model’s uncertainty estimates assume less variability than the data contain. The primary endpoint is described as a number of participants with an event, rather than a rate of repeated events, and no model-based analysis or dispersion estimate is reported in the registry record. It would therefore be inappropriate to infer that a particular count model or over-dispersion adjustment was used.
Multiplicity arises when many outcomes or statistical tests are considered. If many tests are conducted, the chance of at least one apparently notable result can increase unless the analysis accounts for the testing strategy. The registry lists several secondary lipid outcomes, including percent and absolute changes in LDL-C, Apo B, non-HDL-C and total cholesterol over time, as well as an antibody objective. The registry record does not report a multiplicity adjustment, a hierarchy among these outcomes, or test results for them in the information summarized. It is not possible to infer which outcomes were formally tested or how their interpretation was controlled.
Missing-data methods are another part of an analysis plan. General approaches can include defining how incomplete follow-up is handled, modeling available measurements, or applying assumptions about unobserved outcomes. Each approach relies on assumptions that affect interpretation. The registry record does not report the missing-data method for the outcomes summarized, nor does it give a detailed account of missing observations or follow-up completion by outcome. No particular handling method should be assumed.
Sample-size calculations are planning tools, not observed results. Any planning illustration based on an observed effect is a hypothetical exercise rather than the design justification for this study. The stated illustration assumptions 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 fraction of the observed effect. Those assumptions do not describe this single-group study, which has no two-arm allocation. The registry record does not report the trial’s own sample-size justification or a power calculation. A planned sample size also cannot be interpreted as observed power, which is not a measure of the uncertainty in the results actually recorded.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists multiple secondary outcomes, including percent and absolute changes over time in LDL-C, Apo B, non-HDL-C and total cholesterol, as well as assessment of anti-evinacumab antibodies. Considering multiple outcomes raises a general multiplicity issue: separate tests can increase the chance of finding an apparently notable result by chance. The registry record does not report a testing hierarchy, multiplicity adjustment, or a detailed statistical plan for these outcomes. It also does not report numerical secondary-outcome analyses in the information summarized.
Missing-data handling is not reported in the registry record. The record does not specify how incomplete follow-up, unavailable measurements, or withdrawal from treatment were handled in the analysis. This matters because the amount and pattern of missing information can affect the interpretation of longitudinal outcomes and safety follow-up. No assumptions about missingness or imputation should be read into the reported counts.
The defined safety analysis set includes participants who were enrolled and received at least one dose or part of a dose of open-label treatment. That definition identifies who can enter the safety set, but the registry record does not describe other analysis populations or provide detailed participant flow by outcome. It also does not report whether analyses used additional exclusions. The absence of a reported detail is not evidence that a particular method was or was not used; the method is simply not reported in 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 |
|---|---|---|---|
| Overall | 27 | 116 | 23.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Overall | 2 of 116 |
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 |
|---|---|
| Overall | 79 of 116 |
Most frequent serious adverse event terms
| Event term | Organ system | Overall |
|---|---|---|
| Angina pectoris | Cardiac disorders | 2 of 116 |
| Angina unstable | Cardiac disorders | 2 of 116 |
| Aortic valve disease | Cardiac disorders | 2 of 116 |
| Coronary artery disease | Cardiac disorders | 2 of 116 |
| Chest pain | General disorders | 2 of 116 |
| Acute myocardial infarction | Cardiac disorders | 1 of 116 |
| Atrial fibrillation | Cardiac disorders | 1 of 116 |
| Cardiac arrest | Cardiac disorders | 1 of 116 |
| Cardiac failure acute | Cardiac disorders | 1 of 116 |
| Cardiac failure chronic | Cardiac disorders | 1 of 116 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Overall |
|---|---|---|
| Nasopharyngitis | Infections and infestations | 23 of 116 |
| COVID-19 | Infections and infestations | 19 of 116 |
| Headache | Nervous system disorders | 19 of 116 |
| Influenza like illness | General disorders | 17 of 116 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 15 of 116 |
| Nausea | Gastrointestinal disorders | 14 of 116 |
| Back pain | Musculoskeletal and connective tissue disorders | 14 of 116 |
| Cough | Respiratory, thoracic and mediastinal disorders | 12 of 116 |
| Gastroenteritis | Infections and infestations | 10 of 116 |
| Urinary tract infection | Infections and infestations | 10 of 116 |
Serious events with the highest arm-level rate: angina pectoris (1.7%), angina unstable (1.7%), aortic valve disease (1.7%), coronary artery disease (1.7%), chest pain (1.7%).
The registry reports 27 participants in the serious adverse-event category and 79 in the other adverse-event category, with 116 at risk in each category. These figures count participants in the respective categories, not the total number of event episodes. The record lists serious-event terms with percentages: Angina pectoris, Angina unstable, Aortic valve disease, Coronary artery disease and Chest pain are each 1.7%; Acute myocardial infarction is 0.9%. It also reports 2 deaths.
The record does not explain in the information summarized whether participants could appear under multiple serious-event terms, how the percentages were calculated, or whether the deaths were considered related to treatment. Serious adverse events and treatment-emergent adverse events are not interchangeable labels, and a summary of selected serious-event terms does not describe every event or its clinical course. These are descriptive safety observations from a single-group study; they do not, on their own, establish causation or comparative risk.
12. What the Result Does, and Does Not, Mean
The results matter as a descriptive account of safety events recorded during a long-term, open-label study of evinacumab in participants with homozygous familial hypercholesterolemia. The study’s stated objectives include safety and tolerability in participants and adolescent patients, alongside secondary objectives concerning lipid parameters and potential anti-evinacumab antibodies. The registry reports serious and other adverse-event participant counts, selected serious-event terms, and deaths.
The findings do not answer how these counts compare with what would have occurred under another treatment or without treatment. The study has no concurrent comparator and no masking. Events observed during treatment cannot automatically be attributed to treatment, because the design does not separate treatment effects from underlying illness, other care, or changes over time. The record also does not report a separate numerical result for the primary endpoint in the information summarized.
The registry lists lipid outcomes, but numerical results and comparative estimates for those outcomes are not reported in the registry record. It is therefore not possible to characterize the magnitude or precision of lipid changes from the information summarized. The listed adverse-event counts likewise do not establish whether treatment is beneficial or harmful relative to an alternative, and they do not prove that an individual event was treatment-related.
In general, a registry entry records a study’s design and reported results; it is not a substitute for details that are absent from the record, such as event narratives, analysis methods, or uncertainty estimates. The appropriate interpretation is bounded by what is reported: observed participant counts during follow-up, in a single-group study, without a direct comparison. Nothing in these results is medical advice or an individual assessment.
13. Why This Trial Matters Statistically
This study is statistically notable because it addresses long-term safety in a population with homozygous familial hypercholesterolemia, while its single-group design shapes what can be concluded. A prolonged follow-up window can capture events occurring over time, but longer observation does not by itself provide a counterfactual comparison. Without a control group, the study can describe events among participants receiving open-label evinacumab but cannot estimate how event experience would differ under another treatment.
The distinction between a participant count and an event count is also important for interpreting safety summaries. Counts of participants with events describe how many people were affected according to the recorded categories; they do not show whether some people experienced repeated events, how long events lasted, or when they occurred. Selected event-term percentages add detail but do not replace a complete account of the event patterns or their uncertainty.
Finally, the registry’s stated secondary objectives extend beyond safety to lipid outcomes and antibody development, while the information summarized does not report numerical analyses for them. This illustrates why a registry’s outcome list and its result detail must be distinguished. The design and reported data support a descriptive reading, while missing comparative estimates, uncertainty measures and analysis details constrain stronger statistical conclusions.
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 design limitation is the absence of a concurrent comparator. Because the study is single-group and open-label, event counts cannot be contrasted with a randomized control group, and observed events cannot be attributed to treatment solely from their occurrence during follow-up. The registry record does not report a comparative analysis that adjusts for other influences.
The record reports counts in serious and other adverse-event categories but does not provide event-level detail in the information summarized. It does not describe recurrence, timing, duration, outcomes, or the relationship of the reported deaths to treatment. The serious-event percentages are listed for selected terms, but their calculation basis and overlap across terms are not explained. These gaps limit interpretation of severity and patterns beyond the reported summary.
The primary endpoint is defined as participants with treatment-emergent adverse events up to Week 216, but a separate numerical result for that endpoint is not reported in the registry record. Confidence intervals and other uncertainty estimates are also not reported in the information summarized. Without them, the precision of the event-count estimates is not directly described.
The registry record does not report detailed statistical methods, missing-data handling, a multiplicity strategy, or the trial’s sample-size justification. It also does not provide participant characteristics or outcome-specific follow-up detail in the information summarized. The study objectives include adolescent patients, but the number and outcomes of adolescent participants are not reported. These limitations do not invalidate the descriptive counts; they define the boundaries of what those counts can support.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluate the Long-Term Safety and Efficacy of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia — NCT03409744.
- Registry record last updated 2025-04-08; status last verified 2025-04.
- Results first posted 2024-04-30.
- 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
NCT03409744 is a completed phase 3, open-label, single-group study of evinacumab in participants with homozygous familial hypercholesterolemia. The registry records enrollment of 116, a start date of 2018-03-13, and a primary completion date of 2023-04-13. The primary endpoint is the number of participants with treatment-emergent adverse events up to Week 216. The safety analysis set includes enrolled participants who received at least one dose or part of a dose of study treatment.
The registry reports 27 participants in the serious adverse-event category, 79 in the other adverse-event category, and 2 deaths. It lists selected serious-event terms and percentages. The record does not report a concurrent comparison group, a separate numerical result for the primary endpoint in the information summarized, or detailed statistical methods and uncertainty estimates. The study’s secondary objectives include lipid outcomes and potential anti-evinacumab antibodies.