A PK/PD Study of CM4620-IE in Patients With Acute Pancreatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A PK/PD Study of CM4620-IE in Patients With Acute Pancreatitis (NCT03709342), a na phase 2 study. The primary outcome is Exploratory: Percentage Change in IL-2 Production Relative to Pre-dose Values.

2. Clinical Question

This design addresses an early pharmacodynamic and pharmacokinetic question rather than a comparative efficacy question. With no control group, a change from baseline would describe measurements made after dosing in enrolled patients; it would not, by itself, separate any treatment-associated change from natural changes over time, measurement variation, or other influences. The planned dose could also differ for patients treated after the initial five, depending on the PK and PD data. The record does not report whether that conditional dose change occurred or which dose each participant received.

3. Trial Design

This was a phase 2, open-label, single-group study of CM4620-IE in patients with acute pancreatitis. The registry lists CalciMedica, Inc. as the sponsor and reports enrollment of 7. The study began on 2019-01-06, had a primary completion date of 2019-03-07, and is listed as completed. Allocation is recorded as not applicable, consistent with the absence of a randomized treatment-group comparison. The intervention is CM4620-IE, described as a drug.

The study summary describes a continuous intravenous infusion on Day 1. The first five patients were to receive at most 2.08 mg/kg. If necessary, up to an additional 4 patients could be treated at a different dose, selected using the PK and PD data obtained. The infusion was to begin within 12 hours after informed consent from the patient or legally authorized representative. The registry does not report whether a different dose was used, how dose decisions were implemented, or participant-level dose information.

The planned measurements included pharmacodynamic and pharmacokinetic assessments. The primary outcome concerned percentage change in IL-2 production relative to pre-dose values. Listed secondary outcomes include treatment-emergent adverse events, CM4620 concentration measurements at specified post-infusion times, and IL-6 measurements. The registry does not report numerical results for these listed outcomes except for the adverse-event summary described separately.

Because the study has a single group and is open-label, the design can describe observed measurements and safety events among treated patients but cannot estimate a randomized between-group treatment effect. The registry record does not report a statistical analysis plan, a sample-size justification, or a protocol for deciding whether to change the dose. Those details should not be inferred from the conditional dosing description alone.

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

Analysis population for the primary outcome, as defined in the registry: The final analysis set consisted of pre-dose to Discharge samples for 4 patients, due to logistical issues in timely assaying of the samples.

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 Exploratory: Percentage Change in IL-2 Production Relative to Pre-dose Values, measured over Predose to 30 minutes post dose.

The primary endpoint is labeled exploratory and measures percentage change in IL-2 production relative to pre-dose values after administration of a single dose of CM4620-IE. The stated timeframe is pre-dose to 30 minutes post-dose. The endpoint description says the measure was intended to explore whether IL-2 levels changed after administration in patients with acute pancreatitis. The record identifies the summary measure as a mean and the dispersion measure as a standard error.

IL-2 production is a pharmacodynamic measurement: it concerns a biological response measured around dosing, rather than a clinical outcome such as symptom improvement or recovery. A pre-dose reference lets the investigators describe change relative to each patient’s baseline measurement. That comparison does not create a control group, and it cannot by itself establish that a change was caused by the drug.

The registry record does not report the numerical mean percentage change, its standard error, a confidence interval, or a hypothesis test for the primary outcome. It also describes the final analysis set as pre-dose to Discharge samples for 4 patients, due to logistical issues in timely sample assays. This wording does not align cleanly with the stated 30-minute post-dose timeframe. The record does not explain the relationship between the planned timeframe and the samples used in the final analysis, so the endpoint’s actual assessment timing is not fully clear.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary endpoint as a continuous measure: percentage change in IL-2 production relative to pre-dose values. It specifies the mean as the summary measure and the standard error as the dispersion measure. These choices describe how an outcome would be summarized, but they do not give the outcome’s numerical value. The registry record does not report the mean or standard error for this endpoint.

What does a mean describe?

In general, a mean combines individual measurements into an average on the outcome’s scale. For a percentage-change measure, the mean would describe the average relative change among the measurements included in the analysis. An average does not show the full distribution: individual patients may have values that differ from the mean, and the mean alone does not show whether changes were consistent across patients. The registry does not report patient-level values or a distribution for the primary outcome.

What does a standard error describe?

In general, a standard error describes the statistical uncertainty in an estimated mean. It is not the same as the spread of individual patient measurements. A standard error is useful when considering how precisely a mean has been estimated, but its interpretation depends on the analysis and the data contributing to it. Because no numerical standard error is reported for the primary result, the precision of that estimate cannot be evaluated from the registry record.

How should a confidence interval be understood?

In general, a confidence interval presents a range of values compatible with an estimate under the statistical method used. Its width conveys precision, while its position relative to a reference value can help readers assess which values remain plausible. No confidence interval for the primary outcome is reported in the registry record. It would therefore be inappropriate to describe the result as precise or imprecise based on an interval that is not available.

What is the role of the pre-dose comparison?

A before-and-after measurement uses the pre-dose value as a reference for the post-dose value. In general, measuring the same person at both times can account for stable differences between people when describing change. However, a pre-dose reference is not equivalent to an untreated control group. Changes over time, measurement conditions, disease course, or other concurrent influences may also contribute. The record describes no randomized comparison that would distinguish these explanations.

Why does the analysis set matter?

The registry says the final analysis set comprised pre-dose to Discharge samples for 4 patients because of logistical issues in timely sample assays. An analysis set is the collection of observations used for a particular result. If some enrolled patients do not contribute to an endpoint, the result describes the analyzed observations rather than automatically representing everyone enrolled. In general, missing observations can affect interpretation if availability is related to measured outcomes or patient characteristics. The record does not describe the missing-data mechanism, a method for handling missing samples, or an analysis including all enrolled patients.

The stated timeframe also warrants attention. The endpoint is described as pre-dose to 30 minutes post-dose, whereas the analysis-population description refers to pre-dose to Discharge samples. These descriptions may refer to different intended or actual measurement times, but the registry does not explain the distinction. Without clarification, readers cannot determine precisely which sample timing underlies the final analysis.

What can the design estimate?

In general, a single-group study can report observed outcomes after treatment and changes from baseline. It cannot estimate a randomized contrast against a concurrent control group when none is included. Open-label status also means that treatment and assessment are not masked as described in the registry. The record does not describe blinded outcome assessment or a statistical adjustment that would provide a controlled treatment comparison. These design features do not invalidate descriptive measurements, but they limit the causal interpretation of changes.

How should the planning illustrations be read?

The stated planning assumptions describe a hypothetical two-arm calculation using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is framed as a stated fraction of the observed effect. This is a planning exercise, not an analysis of observed power. Its two-arm assumptions do not match the registry’s single-group design, and the registry record does not report a numerical observed primary effect from which readers could assess the illustrations. Planning sample sizes describe what a hypothetical design might require under its assumptions; they are not results from this study.

The record lists no analyses. It also does not report a prespecified statistical plan, an interim-analysis plan, or a sample-size justification. Such details cannot be reconstructed from the choice of a mean and standard error or from the outcome description. In general, statistical methods should be interpreted alongside the planned estimand, timing, missing-data rules, and analysis population; those elements are not fully reported for this primary outcome.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcome domains, including the exploratory primary IL-2 measure, treatment-emergent adverse events, pharmacokinetic measurements, and IL-6 measurements. When a study evaluates multiple outcomes or time points, multiplicity can arise: in general, testing many hypotheses can increase the chance of observing a nominally unusual result even when no corresponding effect exists. Whether and how to address that issue depends on the analysis plan. The registry record does not report a multiplicity adjustment, a hierarchy among outcomes, or a statistical analysis plan, so no correction or prioritization should be assumed.

The record lists no analyses and does not report a numerical primary endpoint result. It therefore does not provide a set of reported tests or p-values from which to assess multiplicity in practice. The endpoint is explicitly exploratory, which is important context: exploratory measurements can inform further questions, but they do not on their own confirm a prespecified treatment effect.

Missingness is directly relevant to the primary outcome. The final analysis set is described as pre-dose to Discharge samples from 4 patients, with logistical issues in timely sample assays given as the reason. The registry does not report the number or characteristics of patients whose samples were unavailable for this analysis beyond the stated analysis population and enrollment. It does not describe an imputation method, a sensitivity analysis, or assumptions about why samples were missing or delayed. Consequently, the possible impact of missingness on the result cannot be assessed.

The record also does not describe a broader analysis population beyond the stated final analysis set, or explain how participants with incomplete measurements were handled in secondary outcomes. These omissions do not show that a particular method was or was not used outside the registry description; they mean the method is not reported in the registry record. Interpretation should remain limited to the information the record actually documents.

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: acute pancreatitis (14.3%), respiratory distress (14.3%).

The safety summary lists 7 patients at risk for the serious-adverse-event measure, with 1 affected. For other adverse events, it lists 7 at risk, with 3 affected. The listed number of deaths is 0. Acute Pancreatitis and Respiratory Distress are each reported among the top serious terms at 14.3%.

These figures are descriptive counts and percentages in the study group. They do not compare CM4620-IE with an untreated group or another treatment, because the registry describes a single-group study. The record does not establish that any listed event was caused by the intervention. Nor do the summary figures indicate how long each patient was followed for safety, whether events overlapped across categories, or the severity and timing of every event; those details are not reported in the registry record.

The serious terms require particular care in interpretation. Acute Pancreatitis is also the condition under study, and the registry lists it as a serious adverse-event term. The record does not provide enough detail to determine the event’s course or relationship to treatment. The two percentages should be read as the registry’s reported term frequencies, not as comparative risks or evidence of causation. With a small enrolled group and no control arm, the safety summary is a description of reported events, not a controlled estimate of treatment-associated harm.

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

The result that can be interpreted directly is primarily about what the registry planned to measure and which patients contributed to the described analysis. The primary endpoint was exploratory, concerned percentage change in IL-2 production relative to pre-dose values, and was intended to examine a biological response after a single dose of CM4620-IE. The final analysis set is described as samples from 4 patients, with logistical issues in timely assays given as the reason.

The numerical primary result is not reported in the registry record. As a result, readers cannot tell whether the average percentage change was above or below baseline, how large it was, or how uncertain the estimate was. The record’s identification of the mean and standard error as summary measures does not substitute for their numerical values. Absence of a reported estimate is not evidence that the measured change was zero or that no change occurred.

Even if a numerical before-and-after change were available, the single-group open-label design would not establish that CM4620-IE caused it. A baseline comparison can describe measurements after dosing relative to earlier measurements, but changes in disease status, timing, assay conditions, or other factors could also contribute. A randomized comparator is not described in the registry record.

The analysis-population description also complicates interpretation because it refers to pre-dose to Discharge samples, while the primary timeframe is listed as pre-dose to 30 minutes post-dose. The record does not resolve that difference. It also does not report how missing or delayed samples were handled beyond identifying the final analysis set and the logistical issue.

The adverse-event summary documents events among enrolled patients, including serious events, other events, and no deaths as recorded. It is not a comparative safety analysis, and the record does not attribute events to the intervention. The available information supports cautious description of the study’s outcomes and reporting limitations, not a conclusion about clinical benefit, lack of benefit, or comparative safety.

13. Why This Trial Matters Statistically

This study raises several statistical interpretation issues that are important in early pharmacodynamic and pharmacokinetic research. First, its primary measure is exploratory and biological rather than a patient-centered clinical outcome. Such a measure can be useful for describing a response around dosing, but its meaning depends on how it is measured, when samples are collected, and how completely the intended sample set is available. The registry record does not provide the numerical primary result or clarify the discrepancy between the stated 30-minute timeframe and the analysis population’s reference to Discharge samples.

Second, the study is single-group and open-label. That design can document observations after dosing, but it cannot furnish a randomized treatment comparison. A within-patient baseline can provide a reference for change, yet it does not eliminate time-related or measurement-related explanations. This distinction is essential when interpreting a pharmacodynamic result: evidence of a measured change and evidence that an intervention caused a change are different statistical claims.

Third, the primary analysis population is limited to 4 patients, whereas enrollment is reported as 7. The registry gives logistical assay delays as the reason. When an endpoint depends on available biological samples, missingness and timing are part of the statistical evidence, not merely administrative details. The record does not describe whether missingness was related to the values that would have been measured or whether sensitivity analyses were conducted.

Finally, the study’s conditional dosing description and its single-group design matter for any planning comparisons. The stated planning assumptions concern a hypothetical two-arm design, not the observed design. Sample-size illustrations under those assumptions are prospective planning aids, not observed power and not proof that this study could or could not detect a particular effect. Together, these features make transparent reporting of endpoint timing, analyzed samples, estimates, and uncertainty especially important.

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.

Several limitations are specific to the registry information for this study. Most importantly, the primary endpoint is described but its numerical result is not reported. The record gives neither the mean percentage change nor its standard error, confidence interval, or statistical test. As a result, the primary pharmacodynamic finding cannot be evaluated for direction, magnitude, or precision.

The record says the final analysis set consisted of pre-dose to Discharge samples for 4 patients because of logistical issues in timely sample assays. It does not explain the timing of the samples in relation to the endpoint’s stated pre-dose to 30 minutes post-dose timeframe. The relationship between those descriptions is not reported in the registry record. The number of analyzed patients is therefore clear as stated, but the exact measurement contrast used is not fully clear.

The study enrolled 7 and has no described control group. Open-label, single-group observations cannot distinguish a treatment-associated change from other changes over time or measurement variation. The conditional dose description indicates that a different dose could have been used for additional patients if necessary, but the record does not say whether that happened or give the doses actually received. No participant-level results are reported.

The registry does not report a statistical analysis plan, sample-size justification, missing-data method, sensitivity analysis, or multiplicity approach. It also does not provide detailed safety-event timing, duration, or treatment relationship. These details may exist outside the registry record, but they are not reported in the registry record and should not be assumed when interpreting the posted information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A PK/PD Study of CM4620-IE in Patients With Acute Pancreatitis — NCT03709342.
• Registry record last updated 2022-05-03; status last verified 2022-02.
• Results first posted 2022-05-03.
• 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 identifies NCT03709342 as a completed phase 2, open-label, single-group study sponsored by CalciMedica, Inc. It reports enrollment of 7 patients with acute pancreatitis. The study began on 2019-01-06, with primary completion on 2019-03-07.

The intervention was CM4620-IE by continuous intravenous infusion on Day 1. The primary endpoint was exploratory percentage change in IL-2 production relative to pre-dose values, summarized as a mean with standard error. The final analysis set is described as pre-dose to Discharge samples from 4 patients because of logistical issues with timely sample assays. The registry record does not report a numerical primary result and does not clarify the difference between that analysis description and the stated 30-minute post-dose timeframe.

The safety summary reports 1 patient affected by serious adverse events, 3 affected by other adverse events, and 0 deaths. Acute Pancreatitis and Respiratory Distress are each listed at 14.3% among the top serious terms. These figures are descriptive and come from a single-group study; they do not provide a controlled comparison.