CER-001 Therapy as a Novel Approach to Treat Genetic Orphan Diseases: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CER-001 Therapy as a Novel Approach to Treat Genetic Orphan Diseases (NCT02697136), a randomized phase 3 study. The primary outcome is Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, multicenter, double-blind, parallel-group, placebo-controlled study. The registry describes masking as quadruple. Its official title specifies a 48 Week study, while the primary endpoint was assessed from baseline to Week 24. The listed study status is terminated. The registry record gives a start date of 2015-12 and a primary completion date of 2018-10; it does not report the reason for termination.

The registry lists enrollment of 30. Participants were assigned to CER-001 or placebo. The CER-001 arm received 9 weekly intravenous infusions followed by 20 biweekly infusions. The placebo arm received saline on the same schedule. The brief summary describes assessment of carotid vessel wall area using 3TMRI in patients with familial primary hypoalphalipoproteinemia, proven cardiovascular disease, and appropriate background lipid-lowering therapy.

The primary endpoint population was defined as modified intent-to-treat: all randomized patients who had baseline and Week 24 carotid 3TMRI performed. The arm results list 17 participants for CER-001 and 10 for placebo. The registry does not explain the difference between the enrollment figure and the endpoint analysis counts, or identify why some randomized participants may not appear in those counts.

Three secondary outcome entries are posted: change in carotid mean vessel wall area and change in carotid target-to-background ratio. Mean vessel wall area appears twice in the secondary outcome list. The record lists 5 outcome measures and 3 analyses, but the full protocol and detailed analysis plan are not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat -- All patients randomized to treatment who have baseline and Week 24 carotid 3TMRI performed

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 Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery, measured over Baseline to Week 24.

The primary endpoint was change in mean vessel wall area (MVWA) of the carotid artery from baseline to Week 24, measured by 3TMRI and expressed in mm2. It is a continuous imaging measure: each participant’s follow-up value is compared with their baseline value, and the resulting change is summarized for each treatment group.

Carotid vessel wall area is used in this study as an imaging measure of the artery wall. Comparing change between randomized groups addresses whether the average measured change differed over the specified interval under the study conditions. An imaging endpoint can quantify a structural measure without directly establishing how participants feel or function, or whether a clinical event occurred. The registry record does not report a threshold for a clinically important change or explain how a change in this measure relates to later clinical outcomes.

The primary endpoint population included randomized participants with both baseline and Week 24 carotid 3TMRI. This definition makes availability of the required scans part of inclusion in the endpoint analysis. The registry reports least-squares means with 95% confidence intervals and a mixed-model comparison for CER-001 versus placebo.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous because it is a measured quantity, rather than a count of events or a category. The registry reports least-squares means for each arm and a mixed-model estimate of the difference. The least-squares mean is a model-based group mean. Depending on the model, it can account for modeled features of the data; the covariates and exact specification used in this analysis are not reported in the registry record. The reported estimates should therefore be described as model-based, without assuming which adjustments were made.

What does a confidence interval convey?

In general, a confidence interval expresses uncertainty around an estimate under the statistical model and its assumptions. A 95% confidence interval is generated by a procedure designed to cover the true parameter in 95% of repeated samples under those assumptions. It is not a statement that there is a 95% probability that the particular interval contains the true value. Wider intervals indicate less precision than narrower intervals, although precision alone does not determine whether an estimate is clinically important.

For the CER-001 arm, the registry reports a least-squares mean change of -0.3 mm2 and a 95% confidence interval from -1.0 to 0.4. For placebo, it reports 0.5 mm2 with a 95% confidence interval from -0.4 to 1.4. For the difference between arms, the mixed-model result is -0.08 with a 95% confidence interval from -1.9 to 0.4. The comparison interval includes zero, the value corresponding to no difference between arms. It also includes estimates in either direction, so the data do not pin down the direction of the difference with precision.

What does the mixed-model comparison add?

In general, a mixed model can represent relationships among observations and incorporate modeled sources of variation. The exact reason this model was selected, its terms, and its handling of repeated observations are not reported in the registry record. The posted analysis is identified as a mixed models analysis and the comparison parameter as a difference in least-squares means. This supports describing the comparison as model-based, but not inferring unreported model assumptions or adjustments.

The estimate of -0.08 is the reported difference in least-squares means. The 95% confidence interval from -1.9 to 0.4 describes uncertainty around that model-based difference. The p-value is 0.185. In general, a p-value is calculated by comparing the observed data with what would be expected under a null hypothesis, using a specified statistical model. It does not indicate the probability that the null hypothesis is correct, nor does it give the probability that the result will replicate. The registry record does not report the full test specification or a prespecified decision rule for interpreting the p-value.

Why do endpoint population details matter?

The primary population is defined by randomization plus completion of baseline and Week 24 carotid 3TMRI. This means the endpoint analysis is restricted to participants with both required scans, according to the registry definition. In general, analyses limited to participants with observed follow-up measurements can be affected if availability of those measurements is related to treatment assignment, participant characteristics, or outcomes. The record does not report how many participants lacked either scan, why measurements were unavailable, or how missing outcomes were handled beyond the stated population definition.

The listed endpoint counts are 17 for CER-001 and 10 for placebo, while the total enrollment is 30. The record does not report a participant flow explaining those figures. It is therefore not appropriate to attribute the difference to a particular reason, such as withdrawal, imaging failure, or an exclusion decision. Nor does the record establish whether the analysis included every randomized participant under another definition.

What can planning illustrations tell readers?

In general, sample-size calculations describe the number of participants needed under specified assumptions to detect a chosen effect with a stated operating characteristic. The planning illustration associated with this study uses a two-sided significance level of 0.05, equal allocation, and a normal approximation; its target effect is expressed as a fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that a trial had a particular probability of success after the results were known. The registry record does not report the trial’s own sample-size justification, so the illustration should not be mistaken for the original design rationale.

Power depends on assumptions about the target effect, variability, allocation, analysis, and decision threshold. In general, planning around a fraction of an observed effect can help illustrate sensitivity to a smaller target effect, but an observed estimate is uncertain and may not be a reliable design target. The registry record does not report enough information to reconstruct the original sample-size rationale or determine whether the trial’s enrollment was intended to support a particular effect size.

What is not specified?

The registry record does not report the detailed statistical analysis plan, model covariates, missing-data methods, any interim analyses, or a sample-size justification. It also does not report whether adjustment for multiple outcomes or analyses was planned. These omissions limit the ability to assess whether the posted analysis matches the prespecified plan or how sensitive the result might be to alternative reasonable methods. The numerical results can still be described as posted, while those methodological questions remain unresolved.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s analysis as a mixed models analysis of the difference in least-squares means between CER-001 and placebo. The estimate is -0.08, with a 95% confidence interval from -1.9 to 0.4 and p = 0.185. This is the posted model-based comparison for the primary endpoint. The registry does not flag a discrepancy between that analysis and a recalculated result.

No separate unadjusted two-arm estimate is available in the registry record. Consequently, there is no alternative recalculation to use in place of the reported model result. The arm-level least-squares means and their confidence intervals are reported separately, but they do not provide a substitute for the mixed-model contrast or its uncertainty. A reader should not reconstruct a between-arm estimate by subtracting rounded arm values, because the posted comparison comes from a model and may not be equivalent to such arithmetic.

The registry record does not give the detailed model specification, covariates, or full analysis plan. The sponsor’s reported estimate can therefore be quoted and interpreted as the posted analysis, while the specific modeling choices cannot be independently assessed from this record alone.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures and 3 analyses. It also lists 3 secondary outcome entries, including carotid MVWA and carotid target-to-background ratio; the MVWA entry appears twice. These counts establish that more than one outcome or analysis is represented in the record, but they do not reveal which tests were considered confirmatory, how outcomes were ordered, or whether any multiplicity adjustment was planned. That information is not reported in the registry record.

In general, when several hypotheses are tested, the chance of at least one apparently notable result can increase if each test is interpreted independently. Statistical methods can address this issue, but the appropriate approach depends on the prespecified objectives and analysis plan. No adjustment method, testing hierarchy, or family of hypotheses is reported. The primary comparison should therefore be read as the posted result for the named primary endpoint, without assuming how it fits into a broader inferential strategy.

The primary analysis population includes randomized participants with baseline and Week 24 carotid 3TMRI performed. The registry lists endpoint counts of 17 for CER-001 and 10 for placebo, alongside overall enrollment of 30. It does not report a participant flow, reasons for missing scans, the number with other missing measurements, or an analysis of participants excluded from the primary endpoint population. It also does not report an imputation method or sensitivity analyses for missing endpoint data.

In general, missing-data methods rely on assumptions about why observations are missing and how missing values relate to observed information. Different assumptions can affect estimates, especially when a complete-case population differs from the randomized population. Without the missingness details and analysis plan, the potential effect of missing endpoint data cannot be assessed from the registry record. The record’s definition of the modified intent-to-treat population is informative, but does not by itself describe the missing-data process.

Interim analyses and any associated adjustments are not reported in the registry record. The registry record also does not report whether the primary endpoint analysis was prespecified in a protocol or statistical analysis plan available to readers. These are limits on judging the overall inferential framework, not evidence that any particular procedure was or was not used.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: angina unstable (5.0%), vascular stent stenosis (5.0%), complication associated with device (5.0%), anaphylactic reaction (5.0%), pyelonephritis acute (5.0%).

The registry reports serious adverse events for three groups: CER-001 double-blind treatment, placebo double-blind treatment, and CER-001 open-label treatment. In the double-blind groups, 4 of 20 participants at risk in the CER-001 group had a serious adverse event, while 0 of 10 at risk in the placebo group had one. In the CER-001 open-label group, 0 of 26 at risk had a serious adverse event. The record lists 0 deaths in each of the three groups.

These are counts of participants reported as affected, alongside the number at risk; they are not counts of all event episodes. The open-label group is distinct from the randomized double-blind comparison, and should not be combined with it as if it were another randomized arm. The record does not report the context needed to interpret the open-label group’s relation to the randomized treatment period.

The listed serious adverse event terms are Angina Unstable, Vascular Stent Stenosis, Complication Associated with Device, Anaphylactic Reaction, and Pyelonephritis Acute, each reported with 5.0%. The registry listing does not establish from these figures alone which treatment group each term occurred in or whether terms refer to unique participants. Serious-event counts are descriptive; differences in group size, follow-up, and event definitions matter when interpreting them. The registry record does not provide enough detail to determine comparative safety from these figures alone.

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

The primary result describes a model-based comparison in carotid MVWA change from baseline to Week 24 among participants with the required baseline and follow-up scans. The estimated difference in least-squares means was -0.08, with a 95% confidence interval from -1.9 to 0.4 and p = 0.185. The confidence interval crosses zero and spans estimates in either direction, so the result does not precisely establish the direction or magnitude of a between-group difference.

This result does not establish that the groups had identical outcomes. An imprecise estimate can be compatible with a range of possible differences, including no difference. Conversely, the negative point estimate alone does not establish a meaningful benefit or harm. The registry record does not define a clinically important threshold for MVWA, so the clinical meaning of the estimate’s magnitude cannot be determined from the posted result alone.

The endpoint is an imaging measure, not a reported clinical event. The registry record does not provide evidence that the measured change predicts later outcomes, nor does it report the treatment effect on a broader clinical endpoint. The results also do not answer questions about other populations, treatment schedules, or background therapies beyond the study description.

The safety figures are descriptive counts from the listed treatment groups. They do not by themselves settle comparative safety, particularly because the record presents a separate open-label CER-001 group and does not provide event timing, detailed exposure information, or context for each serious event. Zero deaths are reported in all three groups, but that fact alone does not characterize other safety outcomes.

The study status is terminated, but the reason is not reported in the registry record. The endpoint findings should not be used to infer why the study stopped. Overall, the posted results provide a specific estimate with substantial uncertainty and leave important questions about missing measurements, analysis choices, multiplicity, and clinical relevance unresolved.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it places a model-based continuous endpoint at the center of a randomized comparison. The registry reports both arm-specific least-squares means and a direct mixed-model contrast. Keeping these estimates distinct helps prevent a common interpretive error: treating separate arm means as if they were the same quantity as the model’s between-arm comparison.

The confidence interval is central to understanding the result. The p-value alone does not convey the range of differences compatible with the data, while the point estimate alone does not convey its precision. Here, the comparison interval includes zero and also extends to values on either side of zero. That makes the uncertainty visible and cautions against reducing the result to a categorical claim based only on the sign of the estimate or a single test statistic.

The endpoint population also illustrates why analysis denominators matter. Enrollment is listed as 30, while the primary endpoint results list 17 participants in the CER-001 arm and 10 in the placebo arm. The modified intent-to-treat definition requires both baseline and Week 24 scans, but the registry does not explain the participant flow or missing measurements. Readers therefore need to distinguish the enrolled study population from the population represented in the reported endpoint estimates.

Finally, this record demonstrates the boundary between posted results and a complete statistical assessment. The registry identifies a mixed-model method, but does not report its full specification, a missing-data strategy, multiplicity procedures, or the study’s own sample-size rationale. Those details affect how fully readers can evaluate robustness and prespecification. The record supports careful description of the posted estimate, while leaving those broader methodological judgments open.

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.

Several trial-specific limitations constrain interpretation. The registry lists enrollment of 30 but reports primary endpoint group counts of 17 and 10. Because the endpoint population required baseline and Week 24 carotid 3TMRI, the analysis reflects participants with both scans; the record does not explain the difference in counts or report reasons for missing imaging. This makes it difficult to assess how the analyzed population relates to all randomized participants.

The primary comparison is reported as a mixed-model difference in least-squares means, but the model specification is not described. Covariates, covariance structure, handling of incomplete observations, and sensitivity analyses are not reported in the registry record. Without these details, the estimate can be reported but the model’s robustness cannot be evaluated fully.

The result concerns an imaging endpoint at Week 24, although the official title describes a 48 Week study. The record does not provide a reason for choosing this endpoint time point or a clinically important threshold for change. It also does not establish how change in carotid MVWA relates to clinical outcomes. The secondary outcome list repeats MVWA and includes target-to-background ratio, but the record does not explain the intended outcome hierarchy.

The study is listed as terminated, with no reason reported in the registry record. The registry does not report whether interim analyses were conducted, how multiplicity was handled, or the trial’s own sample-size justification. Those omissions limit conclusions about stopping decisions, the planned testing strategy, and the intended precision of the primary estimate.

Safety reporting includes double-blind and open-label groups, but the figures do not provide event timing or enough context to compare the groups. The open-label group should not be treated as a randomized comparator. Taken together, these limits mean the posted values support a description of the recorded endpoint and adverse-event counts, not a complete evaluation of the study’s conduct or all possible treatment effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CER-001 Therapy as a Novel Approach to Treat Genetic Orphan Diseases — NCT02697136.
• Registry record last updated 2025-07-22; status last verified 2025-07.
• Results first posted 2025-07-22.
• 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

NCT02697136 is a Phase 3 randomized, quadruple-masked, parallel-group, placebo-controlled study of CER-001 for familial hypoalphalipoproteinemia. The official title describes a 48 Week study; the primary endpoint was change in carotid mean vessel wall area from baseline to Week 24 by 3TMRI. CER-001 and saline placebo were scheduled as 9 weekly infusions followed by 20 biweekly infusions. The registry lists enrollment of 30 and status as terminated.

The primary analysis reports a mixed-model difference in least-squares means of -0.08, with a 95% confidence interval from -1.9 to 0.4 and p = 0.185. The endpoint population required baseline and Week 24 scans; arm counts were 17 for CER-001 and 10 for placebo. The registry record does not report the reason for termination, participant flow explaining those counts, detailed model specification, missing-data methods, or multiplicity procedures.