Natural Killer Cell (CYNK-001) Infusions in Adults With COVID-19: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Natural Killer Cell (CYNK-001) Infusions in Adults With COVID-19 (NCT04365101), a randomized phase 1, phase 2 study. The primary outcome is Phase 1: Frequency and Severity of Adverse Events (AE).

2. Clinical Question

3. Trial Design

The study was registered as a Phase I/II trial of CYNK-001 in adults with COVID-19. Its stated purpose was to assess safety and efficacy. The registry record describes a sequential study model, randomized allocation, and no masking. The Phase I and Phase II descriptions differ in their treatment comparisons, so the Phase I safety findings should not be read as results from the planned randomized comparison.

In Phase I, CYNK-001 was given by infusion on Days 1, 4, and 7, with best supportive care. The dose description specifies an initial desensitizing dose of 150 × 106 cells on Day 1 and 600 × 106 cells on Days 4 and 7. The primary outcome measured treatment-emergent adverse events in the safety population, from the first dose through 28 days after the first dose, up to 6 months.

Phase II was described as randomized and open label, comparing the infusion schedule with a control group receiving best supportive care. Random allocation is intended, in general, to support a fair comparison by reducing systematic differences between groups. Open-label means masking was not used; the registry record does not describe further procedures to limit the influence of treatment knowledge on outcome assessment.

The registry record lists 7 enrolled participants and a terminated status. It does not report why the study was terminated, how many participants entered each phase, or whether the planned Phase II comparison was conducted. Those details should not be inferred from the design 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.

Before assignment: Assessed for eligibility: 8 Excluded: 1 Not meeting inclusion/exclusion criteria: 1 Due to early study termination, only 7 participants were enrolled in Phase 1. No participants were enrolled in Phase 2.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population (all participants who received at least one dose of study treatment).

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 Phase 1: Frequency and Severity of Adverse Events (AE), measured over From first dose through 28 days after first dose, up to 6 months.

The primary endpoint is the frequency and severity of adverse events in Phase I. The registry defines treatment-emergent adverse events as events that started or worsened on or after the first dose of study treatment. Events were assessed according to CTCAE version 5.0, and the stated timeframe runs from the first dose through 28 days after the first dose, up to 6 months.

This endpoint is used to characterize safety during treatment and follow-up. Recording both how often events occur and how severe they are can describe different aspects of tolerability: event frequency alone does not convey severity, while severity alone does not describe how many participants experienced events. In general, safety outcomes are especially important in an early-phase study because they help describe observed harms and inform further study planning. That general purpose does not make the endpoint a measure of treatment benefit.

The primary result is expressed as counts of participants with events. The registry record does not provide a severity-by-grade breakdown or an estimate of comparative risk against a control group. The listed outcome is specifically for Phase I, so it cannot establish whether adverse-event patterns differ between CYNK-001 and best supportive care.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a count-based primary safety outcome: the number of participants with treatment-emergent adverse events. The posted safety figures use participant counts and denominators. They are descriptive summaries, not a reported model-based analysis. The record lists 0 analyses, so it does not identify an inferential procedure for the primary outcome or a method for comparing groups.

What does a participant count describe?

A participant count indicates how many people in the stated group experienced an event under the outcome definition. A denominator gives the number considered at risk for that event. In general, these are useful descriptive measures, but they do not by themselves explain why events occurred or whether the frequency would differ under another treatment. For this Phase I outcome, the registry identifies the safety population as participants who received at least one dose. The posted adverse-event figures report 7 participants at risk.

The event categories should be interpreted as recorded rather than combined into a single total. The registry reports serious adverse events and other adverse events separately, but it does not state whether the same participant could appear in both categories. Adding the counts would therefore risk double-counting. The record also does not give participant-level event histories or a complete listing of all event types and grades.

Why does uncertainty matter?

In general, a count from a small group can be sensitive to each observed outcome. A proportion calculated from such data may look specific, yet still be compatible with a broad range of underlying event rates. Confidence intervals are one way to express that uncertainty. They describe a range of values compatible with the observed data under a stated statistical method; they do not guarantee that the true value lies in the range.

No confidence intervals or other uncertainty estimates for the safety counts are reported in the registry record. No statistical method for deriving such estimates is specified. Consequently, the posted counts support a description of what was observed in the recorded Phase I group, not a precise estimate for other populations.

Can the randomized design support a treatment comparison?

In general, randomized allocation can support causal comparisons when outcomes are collected and analyzed for the assigned groups according to a stated plan. The registry describes Phase II as randomized and open label, with CYNK-001 compared against best supportive care. However, it does not report Phase II group enrollment or outcome results. A design description alone is not evidence that a comparison was completed, and the Phase I counts cannot substitute for randomized comparative results.

Masking was listed as none. In general, knowing a treatment assignment can affect participant reporting, clinical decisions, and outcome assessment, depending on the outcome and how it is measured. Randomization does not itself remove those possible influences. The registry record does not describe procedures for independent outcome assessment or other safeguards against assessment bias.

What can planning calculations say?

In general, a sample-size calculation illustrates how much information a future study might need under stated assumptions. It is a planning exercise, not an observed result, and it does not establish that a study had adequate power after the fact. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. Those assumptions are described as an illustration rather than the trial's own design.

The registry record does not report the trial's sample-size justification or explain the choices in its original design. It also does not report a comparative observed effect on which to base interpretation of a planned efficacy comparison. The planning assumptions should not be mistaken for evidence that the Phase II comparison occurred, nor for observed power.

How should multiplicity and analysis choices be understood?

In general, testing many outcomes or making repeated comparisons can increase the chance of a misleading positive result if the analysis does not account for multiplicity. A prespecified analysis plan can clarify which outcome is primary, how secondary outcomes will be handled, and which comparisons are confirmatory. The registry record names a primary safety outcome and all-cause mortality as a secondary outcome, but does not report a multiplicity procedure or an analysis plan. With no analyses listed, it is not possible to assess whether any multiplicity adjustment was used.

The record does not report how missing outcome data were handled, whether outcomes were assessed at all planned times, or whether any participants were excluded from an analysis. The stated safety population definition gives an inclusion rule based on receiving at least one dose, but does not document the completeness of follow-up. These missing methodological details limit interpretation of both the safety summaries and any intended efficacy assessment.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Phase I")
n      <- c(7)
events <- c(6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Phase I  7  6  85.7  42.1  99.6  48.7  97.4  47.3  96.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies the Phase I adverse-event measure as the primary outcome and all-cause mortality as a secondary outcome. It lists 2 outcome measures, but does not report an analysis plan, a multiplicity procedure, or any outcome analysis; the record lists 0 analyses. It is therefore not possible to determine whether the study planned adjustments for testing multiple outcomes or comparisons.

In general, when several outcomes or contrasts are assessed, the chance of observing an apparently notable result by chance can increase. Prespecifying the primary question and analysis can help distinguish confirmatory results from exploratory findings. The registry record does not provide enough information to determine how that distinction was planned or implemented.

The safety population is defined as all participants who received at least one dose of study treatment. The record does not report how missing safety assessments were handled, whether follow-up was complete, or whether any participants were excluded from outcome summaries. It also does not state how missing data for all-cause mortality or other outcomes were addressed. These details matter because incomplete follow-up can affect both the number observed and the interpretation of event frequencies.

The registry record does not report an intention-to-treat analysis population or another Phase II analysis population. It does not state whether participants were analyzed according to randomized assignment, treatment received, or another rule. Since Phase II results are not reported, the consequences of these absent details cannot be assessed.

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: respiratory failure (14.3%), orthostatic hypotension (14.3%).

The Phase I safety figures report serious adverse events for 2 of 7 participants at risk and other adverse events for 4 of 7 participants at risk. The record lists 1 death. These counts describe the recorded group; the registry does not provide a control-group safety comparison for these Phase I data.

Respiratory failure and orthostatic hypotension are each listed among the most frequent serious-event terms at 14.3%. The registry record does not provide further details about their timing, severity grade, attribution, or whether they occurred in the same participant. It also does not say whether the listed death was related to treatment or to an adverse event.

The serious and other event counts should not be added, because the registry record does not say whether their participant groups overlap. In general, adverse-event counts describe what was recorded, while attribution and comparison are needed to assess possible relationships to treatment. The counts alone do not establish causation or quantify risk relative to best supportive care.

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

The Phase I result documents recorded adverse events among participants included in the safety population. It gives counts for serious and other adverse events, lists a death, and identifies respiratory failure and orthostatic hypotension as serious-event terms reported at 14.3% each. This is a descriptive account of the posted safety information.

It does not establish that CYNK-001 caused any event. The registry record does not report event attribution, a Phase I comparator, or information that would separate treatment-related events from events associated with the underlying illness or other circumstances. It does not provide confidence intervals, detailed event grades, or participant-level overlap between event categories.

Nor does the safety outcome show whether CYNK-001 changes mortality or another measure of disease outcome. All-cause mortality is listed as a secondary outcome, but no result is reported. Although Phase II is described as a randomized, open-label comparison against best supportive care, comparative outcome results are not reported in the registry record.

The study's terminated status and the absence of a reported reason for termination further limit interpretation of what the recorded results represent. The registry record does not say whether Phase II was conducted or how enrollment was distributed across phases. Accordingly, the posted information can characterize the recorded Phase I safety counts, but cannot answer the intended comparative efficacy question or establish how broadly the findings apply.

14. Why This Trial Matters Statistically

This trial is statistically notable because its registry description spans an early-phase safety assessment and a planned randomized comparison. Those are different evidentiary tasks. Safety counts can describe events observed during treatment and follow-up, while a randomized comparison is needed to estimate how outcomes differ between assigned treatment strategies.

The record makes the distinction important: the primary outcome is Phase I frequency and severity of adverse events, while Phase II is described as open-label and randomized against best supportive care. The posted safety counts do not provide the comparison required to estimate a treatment effect. Treating them as comparative evidence would conflate a single-group safety description with a randomized contrast.

The small enrollment reported in the registry also underscores the role of uncertainty in interpreting event frequencies. General statistical reasoning indicates that estimates from small groups can be imprecise, even when the observed counts are clearly stated. Without reported confidence intervals or a comparative analysis, the precision of an underlying event rate cannot be assessed from the registry record.

Finally, the terminated status and lack of reported Phase II results show why design descriptions must be distinguished from analyzed outcomes. Randomization may be part of the planned design, but it does not itself provide evidence of a treatment difference. For clinical researchers, the central statistical lesson is to match each conclusion to the population, outcome, and comparison actually reported.

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 omissions limit interpretation. The registry record reports 7 enrolled participants and Phase I safety counts, but does not state how many participants were treated in each phase or whether the planned Phase II comparison took place. The trial is listed as terminated, with no reason for termination reported in the registry record.

The Phase I adverse-event information is limited to participant counts, a death count, and the most frequent serious-event terms. The record does not report event attribution, severity grades by event, timing for individual events, or whether participants could contribute to both serious and other-event categories. It does not provide a control-group safety comparison, confidence intervals, or a statistical analysis of the counts.

The record does not report Phase II efficacy results, despite describing a randomized comparison and listing all-cause mortality as a secondary outcome. It does not give group-specific enrollment, follow-up completeness, missing-data handling, or the population used for any Phase II analysis. These gaps prevent assessment of the planned comparative question.

The registry record also does not report a sample-size justification, a statistical analysis plan, or procedures for addressing multiplicity. Although planning assumptions are described as illustrative rather than as the trial's own design, no reported comparative effect or analysis allows their relevance to be evaluated. The available findings should therefore be interpreted narrowly as the posted Phase I safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Natural Killer Cell (CYNK-001) Infusions in Adults With COVID-19 — NCT04365101.
• Registry record last updated 2026-06-26; status last verified 2026-06.
• Results first posted 2026-06-01.
• 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

The registry record describes a Phase I/II study of CYNK-001 in adults with COVID-19. Phase I assessed the frequency and severity of treatment-emergent adverse events in the safety population. Phase II was described as an open-label randomized comparison of CYNK-001 infusions with best supportive care.

The record lists 7 enrolled participants and a terminated status. Phase I results include serious adverse events for 2 of 7 participants at risk, other adverse events for 4 of 7, and 1 death. Respiratory failure and orthostatic hypotension are each listed at 14.3% among serious-event terms.

All-cause mortality is listed as a secondary outcome, but no outcome analyses or Phase II comparative results are reported. The reason for termination and several details needed to assess missing data, event attribution, and analysis methods are not reported in the registry record.