Phase 2a Study to Assess CIVI 007 in Patients on a Background of Statin Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2a Study to Assess CIVI 007 in Patients on a Background of Statin Therapy (NCT04164888), a randomized phase 2 study. The primary outcome is Assessment of the Pharmacodynamic Effect of CIVI 007.

2. Clinical Question

The study was designed to assess CIVI 007’s clinical profile across several doses, including lipid efficacy, safety, and pharmacokinetics. The primary outcome named in the record concerns pharmacodynamics: change in PCSK9 relative to baseline. Lipid efficacy and adverse events are listed as secondary outcomes. These questions address different aspects of an investigational treatment, and one type of result cannot stand in for another. In particular, a pharmacodynamic measure is not itself a report of clinical benefit.

3. Trial Design

The registry record describes a randomized, triple-masked, parallel-group, placebo-controlled phase 2a study. It lists Civi Biopharma, Inc. as sponsor, hypercholesterolemia as the condition, and enrollment as 49. The study began on 2019-11-11, had primary completion on 2020-06-18, and is recorded as completed.

Participants were evaluated on a stable background of statin therapy, with or without ezetimibe. The intervention arms were CIVI 007 Dose A, Dose B, and Dose C, alongside placebo. Dose A is described as a low dose given twice by subcutaneous injection; Dose B as dose titration by subcutaneous injection; and Dose C as a high dose given twice. Placebo is described as a matching subcutaneous injection given twice. The registry record does not state the dose amounts.

Randomization is intended, in general, to allocate treatment assignment by chance, while masking is intended to limit the influence of treatment knowledge on study conduct or assessment. The record identifies the study as triple masked but does not specify which roles were masked. A parallel design means assigned groups are followed as separate groups rather than participants crossing between treatments. These design labels describe the study structure; they do not establish how completely the design was implemented or how it affected the results.

The listed objectives span pharmacodynamics, lipid efficacy, safety, tolerability, and pharmacokinetics. The record names one primary outcome and lists lipid efficacy and adverse events as secondary outcomes. The registry record does not report the detailed visit schedule beyond the primary outcome’s stated assessment times, the dose amounts, or the allocation numbers by arm. It also does not report a protocol rationale for the enrollment target.

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

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 Assessment of the Pharmacodynamic Effect of CIVI 007, measured over Baseline, D29, D57, D85.

The primary outcome is the pharmacodynamic effect of CIVI 007, expressed as percentage change from baseline in PCSK9. The registry record specifies that the summary measure is the median and that dispersion is described by the full range. Assessments are listed at Baseline, D29, D57, and D85. The record does not report the actual median changes or ranges at those times.

In general, a baseline-relative measure describes how a participant’s post-baseline measurement compares with that participant’s starting value. A percentage change puts that comparison on a relative scale, while the median describes the middle of the observed values rather than their arithmetic average. The full range gives the lowest and highest observed values, but it does not show how values are distributed between those extremes. A range can also be affected by unusually low or high observations.

Pharmacodynamic outcomes are used to assess a biological response to an intervention. They are distinct from clinical outcomes and from pharmacokinetic measures, which concern the movement of a drug through the body. The record’s separate mention of lipid efficacy and pharmacokinetics indicates that these were also areas of interest, but it does not provide their numerical findings in the information recorded for this study. Without the primary endpoint values, the direction, magnitude, and variability of the reported pharmacodynamic response cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods should be read in relation to the outcome being analysed, the summary measure, the comparison, and the time point. The registry record identifies a primary pharmacodynamic outcome and its descriptive summary, but it does not report the numerical results or a detailed statistical analysis plan. The explanations below are general statistical context, not claims about unreported methods used in this trial.

What does a median describe?

In general, the median is the middle value when observations are ordered. It is less sensitive to extreme observations than the arithmetic mean, which can be useful when measurements are skewed or when a small number of values are far from the rest. The median does not describe every feature of a distribution: groups can have the same median but different spreads or shapes. The registry record specifies the median for percentage change from baseline in PCSK9, with the full range as the dispersion measure. It does not report the values needed to assess the observed distribution.

What does the full range add?

In general, a full range reports the smallest and largest observed values. It communicates the span of the data, but it does not show how many observations lie near either end or how tightly values cluster around the median. Because it relies on the extremes, the range can be sensitive to unusual observations and to the number of observations available. A range is not a confidence interval: it describes observed data limits, whereas a confidence interval expresses uncertainty about an estimated quantity under a statistical model. The record does not give numerical ranges for the primary outcome.

Why use percentage change from baseline?

In general, percentage change expresses a follow-up measurement relative to an individual’s baseline measurement. It can make relative changes easier to compare across people whose starting measurements differ. It also introduces dependence on the baseline value: the same absolute change can correspond to different percentage changes for different starting values. Interpretation therefore benefits from knowing the baseline distribution and how missing or unusable measurements were handled. Those details are not reported in the registry record.

How should repeated assessment times be considered?

The primary outcome lists Baseline, D29, D57, and D85. Repeated measurements can describe how an outcome changes over time, but they also create multiple potential summaries and comparisons. A time-specific estimate answers a different question from an overall trajectory or a comparison averaged across time. The registry record does not report whether the analysis treated the repeated measurements jointly, tested each time separately, or selected a particular time for a primary contrast. It would be inappropriate to infer that method from the listed assessment times.

Why does multiplicity matter?

In general, when many statistical hypotheses are tested, the chance of at least one apparently unusual result can increase if each test is considered separately at the same significance threshold. Methods such as family-wise error control or false-discovery-rate control address different goals and can change how results are interpreted. Multiplicity may arise across dose groups, assessment times, outcomes, or combinations of these. The registry record identifies three CIVI 007 dose regimens and multiple assessment times, but does not report a multiplicity procedure, a hierarchy of tests, or which comparisons were confirmatory. The listed six analyses are not described in enough detail to establish their relationship to the primary outcome.

What can a confidence interval tell a reader?

In general, a confidence interval communicates the uncertainty associated with an estimate under the assumptions of the method used to calculate it. A narrow interval indicates greater statistical precision than a wide interval, but precision does not establish clinical importance. The interval’s location relative to a null value may inform a hypothesis test, while the range of effects it allows can be more informative than a p-value alone. The primary endpoint record gives no confidence interval, standard error, or p-value, so this type of precision assessment is not possible for the reported pharmacodynamic measure.

What are the limits of a normal approximation?

The record’s sample-size assumptions describe a planning illustration based on a normal approximation, equal allocation between two arms, and a two-sided significance level of 0.05. In general, a normal approximation uses a mathematical model that can simplify planning calculations. Its suitability depends on the outcome, sample size, variability, and analysis method. The stated planning framework is not evidence that the trial used that model for its outcome analysis. The record does not report the trial’s own statistical plan, and its multi-arm design should not be reduced to an assumed pairwise comparison without further information.

The sample-size assumptions also state that the planning illustration is based on a stated fraction of the observed effect. Such a calculation is a planning illustration, not observed power and not a result from the trial. No numerical illustration values or observed primary effect are reported in the registry information, so no sample-size estimate can be interpreted from it.

10. Multiplicity, Missing Data and Analysis Populations

The registry record describes several potential sources of multiplicity: three CIVI 007 dose regimens, assessments at Baseline, D29, D57, and D85, and more than one outcome area. It lists one primary outcome, with lipid efficacy and adverse events as secondary outcomes. It also reports three outcome measures and six analyses, but does not explain how those analyses correspond to outcomes, groups, or times.

In general, multiple comparisons can increase the chance of a false-positive finding when each test is interpreted independently. A prespecified testing hierarchy or adjustment method can help control that risk, but the appropriate approach depends on the study’s questions and analysis plan. The registry record does not report whether multiplicity was addressed, which comparisons were intended as primary contrasts, or whether any results were adjusted. It would therefore be inappropriate to treat an unspecified comparison as confirmatory.

The registry record does not report how missing endpoint measurements were handled, whether analyses used an intention-to-treat or another analysis population, or how participants were selected for each outcome analysis. Enrollment is recorded as 49, but that does not establish the number with observed data at each time point. The record also does not describe imputation, exclusions, protocol deviations, or sensitivity analyses. These omissions limit assessment of whether the analyzed observations represent the randomized groups and how robust any result would be to incomplete data. No assumptions about the missing-data procedure or analysis population can be made from the available record.

11. 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: alanine aminotransferase increased (8.3%), aspartate aminotransferase increased (8.3%).

The registry record reports serious adverse event counts separately for the three CIVI 007 dose groups and placebo. Dose A lists 1 affected participant among 12 at risk; Dose B lists 0 among 13; Dose C lists 0 among 12; and placebo lists 0 among 12. No deaths are listed in any group. These are counts as recorded, not estimates of comparative risk.

The record also identifies Alanine aminotransferase increased and Aspartate aminotransferase increased among the top serious terms, each reported as 8.3%. It does not identify a group for those term percentages in the information available, so they should not be assigned to a particular arm. The term listing does not provide the full event narrative, onset, duration, severity, or attribution.

In general, safety counts are descriptive and need context, including exposure duration, event definitions, and completeness of follow-up. Counts alone do not establish whether an event was caused by treatment, and zero recorded events do not establish that an event cannot occur. The record also lists other adverse events: 8 in Dose A, 10 in Dose B, 6 in Dose C, and 9 in placebo. It does not provide enough detail in this record to characterize those events or compare their clinical significance.

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

The registry record documents a randomized, triple-masked, parallel, placebo-controlled phase 2a study of CIVI 007 in patients on stable statin therapy, with or without ezetimibe. Its stated primary measure is median percentage change from baseline in PCSK9 at Baseline, D29, D57, and D85. The record identifies the measurement and design, but does not report the numerical primary outcome results. Consequently, the magnitude, direction, variability, and precision of the primary pharmacodynamic response cannot be judged from these details.

The study’s stated scope also includes lipid efficacy, safety, tolerability, and pharmacokinetics. The registry record lists lipid efficacy and adverse events as secondary outcomes, but does not report numerical lipid efficacy findings or pharmacokinetic results in the information available. The safety counts provide a limited descriptive account of serious and other adverse events. They do not, by themselves, establish a causal relationship or resolve differences between treatment groups.

In general, pharmacodynamic measurements can inform whether a biological response was observed, while clinical outcomes address effects that matter directly to patients. These are related but distinct kinds of evidence. A change in a pharmacodynamic measure does not by itself establish clinical benefit, and the record does not provide enough outcome results to connect the primary measure with lipid efficacy or other clinical effects.

The study’s phase and size also matter when considering the scope of inference. A phase 2a trial can contribute information about an investigational regimen, but conclusions depend on the actual estimates, uncertainty, design, and analysis. The record does not report the detailed statistical plan, multiplicity handling, analysis populations, or missing-data methods. It also does not report a protocol-based rationale for the enrollment target. These limits prevent a complete assessment of how firmly any result could be interpreted, even if outcome values were available.

The defensible conclusion from this registry information is therefore about what the study set out to measure and how it was structured, not whether CIVI 007 had a particular effect. The absence of reported endpoint values is not evidence that there was no effect; it means that the size and precision of the effect are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for combining a placebo group with three CIVI 007 dose regimens and a repeated pharmacodynamic outcome. That structure raises practical questions about how to define the principal contrast, how to summarize change over time, and how to interpret several possible dose-and-time comparisons. Those decisions should be specified in an analysis plan, but the registry record does not report the detailed plan or identify a multiplicity procedure.

The primary outcome is described using the median and full range rather than a mean and a variance measure. In general, this pairing communicates a central value and the observed extremes, but does not fully characterize the shape or uncertainty of the outcome distribution. A reader would need numerical results and additional analytic details to evaluate differences between groups or the precision of an estimate. Those primary endpoint results are not reported in the registry record.

The study also illustrates why enrollment totals and outcome-specific denominators should not be treated as interchangeable. The record lists enrollment as 49, while the safety information gives group-specific numbers at risk. It does not report how many participants contributed primary outcome data at each assessment time or how missing data were handled. Such information is important for understanding the evidence supporting any estimate.

Finally, the distinction between pharmacodynamic, lipid efficacy, safety, and pharmacokinetic outcomes is central to statistical interpretation. Each addresses a different question and may require different summaries and comparisons. The registry record names these areas but does not provide complete numerical findings for them. Statistically, the record is therefore informative about the study’s framework and the limits of what can be evaluated, while leaving the treatment-effect estimates and their uncertainty unresolved.

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 principal limitation for interpreting the primary endpoint is that the registry record identifies the measure, summary statistic, dispersion measure, and assessment times but does not report the actual endpoint values. No dose-specific medians, ranges, between-group estimates, confidence intervals, or p-values are available in the record described. The pharmacodynamic effect and its precision therefore cannot be quantified.

The record does not specify the dose amounts or the allocation counts by arm. Although enrollment is listed as 49, the number contributing data to each outcome and visit is not reported. This prevents a direct assessment of the information available for each group and time point. The registry record also does not explain the six listed analyses or how they relate to the three outcome measures.

Details needed to evaluate analysis quality are not reported in the registry record: the statistical analysis plan, the analysis populations, handling of missing data, treatment of protocol deviations, and any adjustment for multiple comparisons. The registry information also does not report the specific masking roles, detailed event definitions, or follow-up duration for safety outcomes. The listed serious adverse event term percentages are not linked to a group in the available information.

These limitations are specific to the information recorded for this study and do not establish that such details were absent from other study documents. They do mean that the registry record alone does not support a full appraisal of effect estimates, safety comparisons, or robustness of the analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase 2a Study to Assess CIVI 007 in Patients on a Background of Statin Therapy — NCT04164888.
• Registry record last updated 2025-02-13; status last verified 2025-02.
• Results first posted 2025-02-13.
• 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.

18. Record Summary

The registry record identifies NCT04164888 as a completed randomized, triple-masked, parallel, placebo-controlled phase 2a study of CIVI 007 in patients with hypercholesterolemia receiving stable statin therapy, with or without ezetimibe. It lists enrollment as 49 and Civi Biopharma, Inc. as sponsor. The study began on 2019-11-11 and had primary completion on 2020-06-18.

Three CIVI 007 dose regimens were compared with placebo. The primary outcome was median percentage change from baseline in PCSK9, with the full range specified and assessments at Baseline, D29, D57, and D85. The registry record does not report the primary endpoint values. It lists lipid efficacy and adverse events as secondary outcomes and gives group-specific adverse event counts, but does not provide complete outcome results or detailed statistical methods. The available record supports describing the study design and measurements, not estimating the primary treatment effect.