Study of REGN1500 in Participants With Homozygous Familial Hypercholesterolemia (HoFH): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of REGN1500 in Participants With Homozygous Familial Hypercholesterolemia (HoFH) (NCT02265952), a na phase 2 study. The primary outcome is Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline (Week 0) to Week 4 in the Main Study Period.

2. Clinical Question

This is a question about change over time among participants receiving REGN1500, not a direct estimate of how the treatment compares with another treatment or with no treatment. Without a control group, any observed change could reflect more than the intervention. The study is listed as Phase 2 and as an open-label, single-arm, proof-of-concept study. Its stated focus is assessing LDL-C reduction in participants with HoFH. The endpoint gives a short-term view through Week 4; the record also lists other LDL-C outcomes over the main study period and an open-label extension, as well as measures of other lipid variables.

3. Trial Design

The registry describes NCT02265952 as a Phase 2, completed, open-label, single-arm study of REGN1500 in participants with homozygous familial hypercholesterolemia. The listed enrollment is 9. The study began on 2015-02-04, and primary completion is recorded as 2016-11-21. Regeneron Pharmaceuticals is named as sponsor. The official title describes evaluation of the safety and efficacy of single and multiple doses, but the available record does not specify a dosing schedule beyond the intervention descriptions.

There is no randomized allocation: allocation is listed as NA, and the study model is single-group. Masking is recorded as none. Participants and investigators therefore were not blinded to treatment assignment. Since there is no comparison arm, the study can describe changes during treatment but cannot separate treatment-associated change from changes that might have occurred over time or from other influences.

The main study period lists REGN1500 250 mg SC/15 mg/kg IV/450 mg SC. The open-label extension lists REGN1500 300 mg SC/20 mg/kg IV. Those descriptions identify the regimens recorded for the respective periods; details about timing, sequence, eligibility for extension, and how participants moved between periods are not reported in the registry record.

The primary outcome is percent change in LDL-C from baseline (Week 0) to Week 4. The record also lists secondary LDL-C outcomes covering baseline-to-Week-4 change, Week-2-to-Week-4 change, changes over time in the main period, and change from baseline (Week 26) to Week 214 in the extension. Other listed outcomes concern Apo B, non-HDL-C, total cholesterol, and Lp(a). The record lists 22 outcome measures. It does not report a numerical primary outcome estimate or a statistical analysis record. Consequently, the design and intended measures can be described, but the efficacy result cannot be reconstructed 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: This study consisted of 2 screening periods: 1st for main study and 2nd for open label extension (OLE) period. Participants on stable background medical lipid-modifying therapy for at least 4 weeks prior to screening, or who didn't undergo lipid apheresis within 4 weeks prior to screening visit, were directly entered into a 2-week screening period.

Main Study Period

Open Label Extension (OLE) Period

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline (Week 0) to Week 4 in the Main Study Period, measured over Baseline (Week 0) up to Week 4.

The primary endpoint is the percent change in low-density lipoprotein cholesterol (LDL-C) from baseline (Week 0) to Week 4 in the main study period. LDL-C was measured using conventional units of mg/dL, while the endpoint expresses change as a percentage. It is a continuous measure, and the registry identifies the reported summary as a mean with standard deviation.

In general, a percentage-change endpoint expresses the change relative to a participant’s starting value, rather than only the absolute difference in concentration. This can make changes easier to describe across participants whose baseline measurements differ. It does not remove the need to consider baseline values, variability, missing measurements, and the way the analysis population is defined. A group mean also does not show how individual participants’ values were distributed; the standard deviation is a measure of spread, not a confidence interval for the mean.

LDL-C is the lipid measure selected for the stated proof-of-concept question. The record also identifies other LDL-C time points and related lipid measures as secondary outcomes. Those additional outcomes can describe different aspects or durations of change, but they do not replace the prespecified primary endpoint. The numerical mean, standard deviation, participant count in the efficacy analysis, and confidence interval for the primary endpoint are not reported in the registry record. Without those results, the size and precision of the measured change cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean represent?

The primary outcome is a continuous measure summarized as a mean. In general, the mean describes the average value across the participants included in an analysis. It condenses the observations into one number, so it does not show whether individual results were clustered near that average or spread widely. The registry specifies standard deviation as the dispersion measure. In general, standard deviation describes the spread of individual observations around the mean; it is not the same as a confidence interval and does not directly express uncertainty in the estimated mean.

For this endpoint, the mean would describe average percentage change in LDL-C over the stated interval among the participants included in the efficacy analysis. Its interpretation depends on which participants contributed data and how the endpoint was calculated. The registry describes the eligibility rule for the efficacy set but does not report the resulting analysis count, numerical mean, standard deviation, or confidence interval.

What does a confidence interval add?

In general, a confidence interval communicates the statistical uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, but neither width nor location can be assessed without the interval itself. A confidence interval is not a range guaranteed to contain the true value, and it does not address every source of bias. In particular, an interval from a single-arm study cannot correct for the absence of a control group.

No confidence interval for the primary endpoint is reported in the registry record. The posted outcome description therefore does not support a trial-specific statement about how precisely the mean change was estimated. A standard deviation, even if reported, would describe variability among observations and would not substitute for an interval around the mean.

Why does the single-arm structure matter?

In a controlled comparison, the difference between groups can help distinguish an intervention-associated outcome from changes that might also occur without the intervention, subject to the design and analysis assumptions. This study is recorded as single-group, with allocation listed as NA and no masking. It has no like-for-like control comparison. A baseline-to-follow-up change is consequently descriptive of the observed group over time, rather than a randomized estimate of treatment effect versus a comparator.

General sources of change in a before-and-after measure include natural variation, measurement error, changes in other care, and regression to the mean. Regression to the mean refers to the tendency for an unusually high or low measurement to be less extreme on a later measurement even without a causal intervention effect. These are general possibilities, not documented explanations for any outcome in this trial. A control group and carefully specified analysis can help address some competing explanations; this design does not include a control group.

What does the planning illustration mean?

Planning calculations are design illustrations, not observed trial outcomes. The registry description for the planning illustration specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses a total event count; for other outcomes, it expresses planning size as participants per arm.

These assumptions describe a hypothetical future comparison and do not change the single-arm design of the completed study. A planning size is not observed power, and it does not show the probability that this trial detected an effect. The registry entries do not include the numerical planning outputs or a numerical observed primary effect. Accordingly, no planning count or effect-based illustration can be interpreted quantitatively from the registry information. The record also does not report that these assumptions were used to design the actual trial.

How should repeated outcomes be considered?

The record lists several assessments of LDL-C, including changes across different intervals and over time, as well as secondary lipid outcomes. Repeated measurements can describe the pattern of a measure over time, but they are correlated because measurements from the same participant are not independent. General methods for repeated measures account for that dependence and may make assumptions about the form of the outcome trajectory and handling of missing observations. The registry does not report which method, if any, was used for those outcomes.

Testing or interpreting several outcomes also raises multiplicity concerns. In general, examining many endpoints can increase the chance of observing an apparently unusual result by chance if each is treated as a separate confirmatory test. Prespecified priorities and suitable adjustment or cautious interpretation can address this issue. The registry record does not report a multiplicity plan or an analysis result for the listed outcomes. No claim about significance across the outcome set can therefore be made.

What is the role of the analysis population?

The efficacy description says that the analysis set included participants in the safety analysis set who had baseline and at least 1 post-baseline lipid-panel measure during the main study period. This rule indicates that participants without the required measurements would not meet that stated efficacy-set criterion. It does not specify whether other analysis populations were used, how missing values were handled, or whether all eligible measurements were included. Those details are not reported in the registry record.

In general, an analysis population affects the meaning of an estimate. An analysis limited to participants with observed follow-up measurements may differ from an analysis that uses a broader population or imputes missing values. Missingness can also affect interpretation if the reasons for missing data are related to outcomes. Without details on missing observations and the analysis method, the direction or size of any resulting bias cannot be assessed. These considerations explain why a stated endpoint alone is not enough to evaluate a result; the estimate, uncertainty, population, and analysis approach are all relevant.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("REGN1500 250 mg SC/15 mg/kg IV/450 mg SC")
n   <- c(9)
m   <- c(-49.17)
sp  <- c(23.136)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  REGN1500 250 mg SC/15 mg/kg IV/450 mg SC  9  -49.170  23.136  -66.954  -31.386

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures. These include the primary LDL-C endpoint, other LDL-C changes over the main study period, LDL-C outcomes during the extension, and changes in Apo B, non-HDL-C, total cholesterol, and Lp(a). In general, examining multiple outcomes creates a multiplicity issue: the chance of finding an apparently noteworthy result can rise when many outcomes are assessed. A prespecified hierarchy, adjustment method, or appropriately cautious interpretation can help address this. A multiplicity strategy is not reported in the registry record.

The registry description defines the efficacy analysis set as participants in the safety analysis set with baseline and at least 1 post-baseline lipid-panel measure in the main study period. The number meeting that definition is not reported. The record does not describe how missing values were handled, whether any imputation was performed, or what assumptions were made about missingness. It also does not identify additional analysis populations or report the primary analysis method.

These omissions matter because the analyzed participants and handling of unavailable measurements can affect an estimated mean and its uncertainty. In general, results based only on observed follow-up may be affected if participants with missing outcomes differ systematically from those with observed outcomes. The registry information does not establish whether such a difference occurred in this study.

The registry lists 22 outcome measures and 0 analysis records. The numerical outcome estimates, uncertainty measures, statistical testing results, and multiplicity procedures are not reported in the registry record. Consequently, the listed endpoints describe what was measured, but do not permit an assessment of which findings, if any, were statistically significant or treated as confirmatory.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: coronary artery stenosis (12.5%), bronchospasm (12.5%), coronary artery disease (11.1%).

For the main study period, the registry reports 9 participants at risk for serious adverse events and 1 affected. Other adverse events are reported for 9 at risk and 9 affected. For the open-label extension period, 8 participants were at risk for serious adverse events and 2 were affected; other adverse events are reported for 8 at risk and 8 affected. The record reports 0 deaths in each period. These are period-specific figures and should not be combined, since the registry does not explain participant overlap between periods.

The record also lists coronary artery stenosis at 12.5%, bronchospasm at 12.5%, and coronary artery disease at 11.1% among the top serious-event terms. It does not provide further context for interpreting those percentages in this summary, including event timing or relatedness to REGN1500. The listed terms should therefore be read as reported safety observations, not as evidence that the intervention caused them.

In general, adverse-event counts describe events observed during a study; a small, uncontrolled study cannot reliably establish comparative risk. The figures do not show whether an event was new, recurrent, mild, or severe beyond its serious-event classification, nor do they provide a comparison with an untreated group. The limited enrollment and absence of a control group constrain safety interpretation.

13. What the Result Does, and Does Not, Mean

The registry record identifies a clinically relevant measurement question: the average percentage change in LDL-C from baseline (Week 0) to Week 4 among participants with HoFH who met the stated efficacy-set criteria. It also records the study as completed and lists the outcomes and intervention periods. However, the numerical primary endpoint result is not reported in the registry record. No average change, standard deviation, confidence interval, or analysis count is available in the posted record. Therefore, the magnitude, direction, and precision of the primary result cannot be assessed from this information.

Even with a numerical before-and-after result, this design would support a descriptive account of change in the treated group, not a randomized comparison. The single-arm structure leaves no control group to distinguish treatment-associated change from other possible causes of change over time. Open-label conduct is another limitation, although a laboratory endpoint is less dependent on subjective symptom reporting than some outcomes. These are design considerations; they do not show that any particular bias occurred.

The record’s additional LDL-C and lipid outcomes can be understood as measurements planned or listed for different intervals and variables. Their presence does not establish that results were favorable, statistically significant, or consistent. Numerical results and analysis methods for these outcomes are not reported in the registry record. The same caution applies to the safety information: event counts and listed terms describe reported observations, but do not establish causation or comparative risk.

Accordingly, the registry information establishes the study’s question, basic design, listed outcomes, and selected safety counts. It does not establish a treatment effect, the precision of an LDL-C estimate, a comparative benefit or harm, or a definitive safety profile. The study’s proof-of-concept purpose should not be mistaken for an efficacy finding; conclusions require outcome estimates and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how a clearly named endpoint can still be difficult to interpret without its result and analysis details. The registry identifies a continuous primary outcome, a baseline-to-Week-4 interval, a mean summary, and standard deviation as the dispersion measure. Those details clarify what the investigators intended to quantify. Yet without the estimate and its uncertainty, readers cannot determine the observed change or how precisely it was measured.

The single-arm design also illustrates the distinction between change and treatment effect. A before-and-after measure can document how outcomes varied during a study period, but it does not provide a randomized counterfactual. Without a concurrent comparison group, the extent to which a measured change is attributable to the intervention cannot be isolated from other possible influences. This is a design limitation, not a claim that the intervention did or did not affect LDL-C.

The registry lists multiple related outcomes and both a main study period and an extension. This makes analysis transparency important: readers need to know which outcomes were primary, how repeated measures and missing data were handled, and whether multiplicity was addressed. The record does not report those methods or numerical efficacy analyses. The sample-size illustration is described as a planning exercise based on a fraction of the observed effect, not as observed power or as the actual design justification.

Finally, the posted safety counts show why event data require context. Period-specific counts and percentages are useful descriptions, but a small uncontrolled study cannot provide a strong comparative assessment of risk. Taken together, the record highlights the value of reporting outcome estimates, uncertainty, analysis populations, missing-data methods, and prespecified statistical choices alongside a trial’s design and endpoint definitions.

15. 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 interpretation is that the registry record does not report the numerical result for the primary endpoint. The estimate, standard deviation, confidence interval, and number analyzed are unavailable, so neither the size nor precision of the outcome can be evaluated. Numerical results for the secondary outcomes are also not reported in the registry record.

The study is single-arm, with allocation listed as NA and masking as none. Without a control group, observed within-participant or group change cannot be separated from other time-related influences. Open-label conduct may also affect behavior, care, or measurement processes. These limitations apply to interpretation of any outcomes and are not evidence that bias necessarily occurred.

The listed enrollment is 9. The efficacy analysis set requires baseline and at least 1 post-baseline lipid-panel measure, but the number meeting that rule is not reported. The registry does not describe missing-data methods, the number or reasons for missing measurements, or whether results were assessed in other analysis populations. These gaps prevent assessment of how the analysis set and unavailable observations might affect the endpoint estimate.

The record lists 22 outcome measures but does not report a multiplicity plan, statistical analysis method, or analysis results. It therefore does not establish how repeated outcomes were modeled or how multiple comparisons were interpreted. Details about the dosing schedule, sequence, and movement into the extension are not reported in the registry record. The safety summaries also lack reported context on event timing and relatedness. These limitations restrict conclusions about efficacy, durability, and comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of REGN1500 in Participants With Homozygous Familial Hypercholesterolemia (HoFH) — NCT02265952.
• Registry record last updated 2019-12-09; status last verified 2019-12.
• Results first posted 2019-12-09.
• 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.

19. Record Summary

NCT02265952 is recorded as a completed Phase 2, open-label, single-arm study sponsored by Regeneron Pharmaceuticals. It enrolled 9 participants with homozygous familial hypercholesterolemia. The start date is 2015-02-04, and primary completion is recorded as 2016-11-21. The primary endpoint is percent change in LDL-C from baseline (Week 0) to Week 4 in the main study period.

The registry lists 22 outcome measures and describes an efficacy analysis set requiring baseline and at least 1 post-baseline lipid-panel measure. It does not report a numerical primary outcome estimate, its uncertainty, or the number analyzed. The study has no randomized control group, and masking is listed as none. Safety counts are reported separately for the main study and extension periods, with 0 deaths recorded for each. The available record supports description of the design and endpoints, but not a quantitative conclusion about efficacy or comparative safety.