This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Phase II/III Study of Sargramostim (NCT04642950), a randomized phase 2, phase 3 study. The primary outcome is 2-rank Improvement on a 7-point Ordinal Scale.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04642950 |
| Phase | Phase 2, Phase 3 |
| Condition | COVID-19 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 70 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Nobelpharma |
| Results posted | Yes |
2. Clinical Question
Population
Patients with coronavirus disease-2019 (COVID-19) are the target population described in the record. The registry lists an enrollment of 70. The primary outcome description does not provide a more detailed analysis population, such as eligibility characteristics for participants whose outcome contributed to the reported median.
Intervention
The intervention was sargramostim inhaled as add-on treatment to standard treatment. The NPC-26 description specifies 125 μg by inhalation twice daily for 5 days in principle, with treatment up to 10 days. The study is described as evaluating efficacy and safety.
Comparator
The comparison was placebo, described as physiological saline given by inhalation twice daily for 5 days in principle, with treatment up to 10 days, also as add-on treatment to standard treatment. The record characterizes the study as placebo-controlled and randomized.
Primary question
The primary endpoint asks how long it takes to achieve at least a 2-rank improvement from baseline on a 7-point ordinal scale, during the period until Day 28, including the case after discharge. The posted medians are 9 days for NPC-26 and 8 days for placebo. Their 95% confidence intervals are 8 to 9 days and 7 to 10 days, respectively. These summaries describe the observed endpoint; by themselves, they do not establish the size or statistical certainty of a treatment effect.
3. Trial Design
This was a randomized, placebo-controlled, parallel-group study in Phase II/III. The registry classifies allocation as randomized and masking as quadruple. Its brief summary also calls the study double-blind. Those descriptions are both part of the record; the registry does not explain how its masking classification relates to the wording in the brief summary. The study is described as a multicenter group comparison.
The treatment contrast was inhaled sargramostim versus inhaled physiological saline, each added to standard treatment. The sargramostim arm is named NPC-26, and the placebo arm is named NP-26 Placebo. The treatment descriptions specify twice-daily inhalation for 5 days in principle, with treatment allowed up to 10 days. The record does not provide further detail about how standard treatment was defined or selected.
The registry reports an enrollment of 70. The outcome entries list 47 participants for NPC-26 and 23 for NP-26 Placebo. These figures describe different record elements; the registry does not explain their relationship or provide a participant flow account in the information available for this analysis.
Nobelpharma is named as sponsor. The reported study start was 2020-12-17, primary completion was 2021-10-25, and the status is completed. The primary outcome was time in days to at least a 2-rank improvement on a 7-point ordinal scale from baseline, evaluated through Day 28, including after discharge. Secondary outcomes include change in the alveolar-arterial oxygen partial pressure gradient, days until discharge from baseline, and the proportion whose category shifted to Category 1 or 2. The registry record does not provide a detailed protocol or a full account of the conduct of the trial.
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
| Stage | NPC-26 | NP-26 Placebo |
|---|---|---|
| STARTED | 47 | 23 |
| COMPLETED | 44 | 23 |
| NOT COMPLETED | 3 | 0 |
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.
| Characteristic | Unit | NP-26 Placebo | NPC-26 | Total |
|---|---|---|---|---|
| Participants analysed | 23 | 47 | 70 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 21 | 35 | 56 |
| Age, Categorical: >=65 years | Participants | 2 | 12 | 14 |
| Age, Continuous | years | 55.9 (SD 8.3) | 54.1 (SD 12.5) | 54.7 (SD 11.3) |
| Sex: Female, Male: Female | Participants | 9 | 9 | 18 |
| Sex: Female, Male: Male | Participants | 14 | 38 | 52 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: Japan | participants | 23 | 47 | 70 |
6. Primary Endpoint
The registry lists the primary outcome as 2-rank Improvement on a 7-point Ordinal Scale, measured over Period until Day 28 (including the case after discharge)..
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Number of Days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is the number of days until a participant achieves at least a 2-rank improvement from baseline on a 7-point ordinal scale. It is assessed over the period until Day 28, and the description explicitly includes the case after discharge. The scale provides an ordered way to represent clinical status; a change in rank captures improvement as defined by the endpoint, rather than measuring a continuous quantity such as oxygen pressure.
The endpoint is expressed as time to an event: the event is reaching the specified improvement threshold. A median time describes the point by which half of the relevant observations have reached that event, subject to the analysis method and handling of observations that have not reached it. It gives a time-based summary, but does not show the full pattern of event times or explain how participants without an observed improvement were treated in the analysis.
The posted median is 9 days for NPC-26, with a 95% confidence interval of 8 to 9 days. For NP-26 Placebo, the median is 8 days, with a 95% confidence interval of 7 to 10 days. The confidence intervals communicate uncertainty around each arm's median; they are not a direct confidence interval for a comparison between arms. The registry record does not report a hazard ratio or another inferential estimate for the treatment contrast.
A time-to-improvement endpoint can summarize how quickly a defined status change occurs during follow-up. Its interpretation depends on the precise event definition, follow-up, censoring, and analysis population. The event definition and follow-up period are stated, but the registry record does not report the analysis details needed to assess the remaining features.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary outcome is reported as a median time to improvement of 9 days in NPC-26 and 8 days in NP-26 Placebo. The corresponding 95% confidence intervals are 8 to 9 days and 7 to 10 days. These are arm-specific summaries. The record does not report a hazard ratio, a confidence interval for a between-arm contrast, or a p-value for this endpoint. Without a reported comparative estimate and its uncertainty, the medians alone do not quantify the precision of the treatment comparison.
The intervals describe uncertainty in the estimated median under the analysis used; they are not ranges containing all individual participants' times. Their overlap does not, on its own, determine whether a comparison is statistically significant. Likewise, the difference in the point estimates should not be interpreted in isolation as a treatment effect. A formal comparison would require an analysis suited to the time-to-event outcome and information about how follow-up and incomplete observations were handled. Such details are not reported in the registry record.
The arm entries include 47 participants in NPC-26 and 23 in NP-26 Placebo. These are the sample sizes associated with the outcome summaries. The registry separately reports enrollment of 70, but does not explain whether all enrolled participants contributed to this endpoint or why the outcome entries have the listed arm sizes. A reader should therefore distinguish the recorded enrollment from the numbers attached to the outcome results, rather than treating them as interchangeable.
The endpoint is described as reaching at least a 2-rank improvement by Day 28, including after discharge. The record does not state how participants who did not achieve the improvement by the end of follow-up were handled, whether any participants were censored, or whether a particular survival-analysis estimator was used. Those decisions can affect medians and their confidence intervals. No alternative adjusted result is reported, and no analysis records are available in the registry record.
The findings should be read as descriptive posted results for the randomized arms, not as proof that the treatments are equivalent or that either approach is superior. The absence of a reported comparative estimate is not evidence that the effect is absent. The registry lists secondary outcomes, but does not provide their results in the record analyzed. Accordingly, those outcomes cannot be used to expand or resolve the interpretation of the primary result.
9. Statistical Methods Explained
The primary endpoint is a time-to-event outcome. In general, time-to-event methods analyze the time until a defined event, while accounting for the possibility that the event is not observed during follow-up. Here, the event is a 2-rank improvement from baseline on a 7-point ordinal scale, and the stated observation period extends until Day 28, including after discharge. The registry identifies the endpoint as a median number of days and reports a 95% confidence interval for each arm.
What does a median time represent?
In general, a median is a central summary: it marks the point at which half of the relevant event-time distribution lies on either side, as defined by the estimation method. It is not an average and does not describe every participant's experience. Two groups can have different distributions even when their medians are similar, and a median alone does not reveal how quickly events occur across the full follow-up period. For this outcome, the posted median is 9 days for NPC-26 and 8 days for NP-26 Placebo.
For time-to-event data, participants whose event is not observed before follow-up ends may contribute partial information rather than a completed event time. This is commonly handled through censoring methods. That general feature is important because simply omitting such participants or assigning them an event time would not be equivalent to a suitable time-to-event analysis. The registry record does not report whether censoring occurred, how it was defined, or which estimator was used for the medians.
How should the confidence intervals be read?
In general, a confidence interval expresses the uncertainty associated with an estimated quantity under the assumptions of the statistical method. The reported 95% confidence interval for the NPC-26 median is 8 to 9 days; for NP-26 Placebo it is 7 to 10 days. These intervals concern the arm-specific medians. They are not confidence intervals for the difference between treatment arms, and they should not be read as a range of individual participant outcomes.
In general, comparing separate confidence intervals is not a substitute for estimating a direct treatment contrast. The apparent overlap or separation of arm-specific intervals does not itself provide the result of a formal hypothesis test. A comparison could be expressed using a time-to-event measure such as a hazard ratio, or another prespecified contrast with an uncertainty interval. No such comparative estimate is reported for the primary endpoint in this registry record.
Why can event-time analysis details matter?
General time-to-event analyses rely on assumptions about follow-up and censoring. Censoring is most straightforward to interpret when the reason an event time is unobserved is not related to the participant's underlying chance of experiencing the event, conditional on the analysis. If that assumption is not reasonable, the estimated event-time distribution may be affected. The record's endpoint description includes follow-up after discharge, but does not explain how discharge, loss to follow-up, or other incomplete observations were represented analytically.
In general, a hazard ratio compares event rates over follow-up under a particular model; it is not a ratio of medians and does not directly state how many days sooner an event occurred. The registry's general outcome type indicates that only sponsor-reported hazard ratios are used, but no hazard ratio is reported for this primary outcome. The posted median summaries should therefore remain distinct from an unreported model-based comparison.
What does over-dispersion mean in general?
Over-dispersion describes variation in data that is greater than a statistical model expects. It is relevant when an analysis assumes a particular amount of variability, because underestimated variation can make uncertainty appear too small. This is a general statistical consideration, not a claim that over-dispersion affected this trial. The registry record does not report a model or diagnostic assessment for the primary time-to-event endpoint, so no trial-specific conclusion about over-dispersion can be drawn.
The outcome entries also report the number of participants associated with each arm's median. In general, the amount of information available for estimating an event-time distribution depends not only on the number of participants, but also on the events observed and the follow-up information. Event counts and individual follow-up summaries are not reported. The registry separately records enrollment of 70, while the arm outcome entries list 47 and 23; the record does not explain the relationship between those figures.
Some posted results can be recalculated from summary statistics when the outcome and data support a simple unadjusted comparison. The registry record explicitly identifies this median-time endpoint as unsuitable for such a two-arm recalculation and reports no analysis results. It would therefore be inappropriate to create a comparative estimate from the two medians or their separate intervals. Any such estimate would require additional data or a sponsor-reported analysis, neither of which is reported in this record.
Planning calculations are also distinct from observed trial results. In general, a sample-size planning illustration describes the number of participants or events that might be needed under stated assumptions; it is not observed power and does not establish the precision of the completed trial. The registry describes planning assumptions based on a stated fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It does not report numeric planning results in the record analyzed. Those assumptions should not be mistaken for a statistical design plan documented for the trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three secondary outcomes: change from baseline in the alveolar-arterial oxygen partial pressure gradient, days until discharge from baseline, and the proportion whose category shifted to Category 1 or 2. The primary outcome and secondary outcomes create the possibility of multiple statistical comparisons. In general, testing many outcomes can increase the chance of at least one apparently notable result, unless the analysis plan addresses multiplicity. The registry record does not report a multiplicity adjustment, a hierarchy among outcomes, or which outcomes were designated for confirmatory interpretation.
The record lists four outcome measures, but does not provide results for the secondary outcomes in the information available for this analysis. It also does not report an interim-analysis plan, stopping boundaries, or a complete statistical analysis plan. These items are not reported in the registry record; their absence should not be taken to mean that a particular procedure was or was not used.
Missing-data handling is not reported in the registry record. For the time-to-improvement endpoint, the record does not explain how participants who did not achieve the improvement by Day 28 were handled, whether there were censored observations, or how any missing outcome information was addressed. In general, these choices can influence both the estimated median and its uncertainty.
The analysis population is also not reported in detail. The endpoint description gives no population label, and the registry does not state whether the analysis followed an intention-to-treat principle, used a per-protocol population, or applied another definition. The outcome entries list 47 participants for NPC-26 and 23 for NP-26 Placebo; the registry enrollment is 70, but no participant flow or reconciliation of these figures is reported.
The record contains no posted analysis records. That limits assessment of prespecified testing, adjustment, model choices, and sensitivity analyses. The absence of these details means the reported medians can be described, but the robustness of the primary comparison cannot be evaluated from the registry record alone.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| NPC-26 | 2 | 47 | 4.3% |
| NP-26 Placebo | 0 | 23 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| NPC-26 | 0 of 47 |
| NP-26 Placebo | 0 of 23 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| NPC-26 | 22 of 47 |
| NP-26 Placebo | 8 of 23 |
Most frequent serious adverse event terms
| Event term | Organ system | NPC-26 | NP-26 Placebo |
|---|---|---|---|
| Myocardial infarction | Cardiac disorders | 1 of 47 | 0 of 23 |
| COVID-19 pneumonia | Infections and infestations | 1 of 47 | 0 of 23 |
Most frequent non-serious adverse event terms
| Event term | Organ system | NPC-26 | NP-26 Placebo |
|---|---|---|---|
| Constipation | Gastrointestinal disorders | 7 of 47 | 4 of 23 |
| White blood cell count increased | Investigations | 7 of 47 | 0 of 23 |
| Hyperglycemia | Metabolism and nutrition disorders | 4 of 47 | 1 of 23 |
| Insomnia | Psychiatric disorders | 1 of 47 | 3 of 23 |
| Hepatocellular injury | Hepatobiliary disorders | 3 of 47 | 0 of 23 |
Serious events with the highest arm-level rate: myocardial infarction (2.1%), covid-19 pneumonia (2.1%).
The adverse-event entries list serious adverse events affecting 2 participants in NPC-26 and 0 in NP-26 Placebo. The corresponding numbers at risk are 47 and 23. Other adverse events are listed for 22 participants in NPC-26 and 8 in NP-26 Placebo, with the same at-risk counts reported for each arm. The record lists 0 deaths in each arm.
These are participant counts, not comparative risk estimates. They should not be converted into percentages or treated as evidence of a treatment difference without a defined analysis. The entries do not give event timing, duration, severity grading beyond the serious-event classification, or the criteria used to determine attribution. The registry record also does not explain whether participants could contribute more than one event to the reported categories.
The listed top serious adverse event terms are myocardial infarction at 2.1% and COVID-19 pneumonia at 2.1%. The record does not associate these terms with a particular treatment arm in the listed information. They should therefore be read as terms appearing in the serious-event summary, not as arm-specific comparative findings.
Safety counts are most informative when interpreted alongside definitions, follow-up completeness, exposure, and the method used to collect events. Those details are not reported in the registry record. The counts describe the posted safety entries, but do not by themselves establish causation or provide a full safety comparison.
12. What the Result Does, and Does Not, Mean
The record provides arm-specific medians for the time to achieve the defined improvement: 9 days for NPC-26 and 8 days for NP-26 Placebo. Their respective 95% confidence intervals are 8 to 9 days and 7 to 10 days. These values describe the reported endpoint summaries. Because the registry does not report a direct comparative estimate or its confidence interval, they do not quantify the uncertainty in the treatment contrast.
The result does not establish that the arms are equivalent. Equivalence requires a prespecified margin and an analysis that evaluates whether the uncertainty around the treatment contrast lies within that margin; such information is not reported in the registry record. Nor does the absence of a reported p-value establish that there was no effect. The record's missing comparative analysis leaves the direction and precision of a formal treatment-effect estimate unreported.
The trial design was randomized and placebo-controlled, with both treatments described as add-ons to standard treatment. Randomization is generally intended to support a fair comparison by balancing prognostic factors across groups, on average. It does not remove the need to describe the analysis population, missing data, follow-up, and statistical model. Those details are not available in the record analyzed.
The secondary outcomes are named, but their results are not reported. The safety entries list serious and other adverse events and deaths by arm, but do not provide enough detail to infer causation or assess differences in risk. Taken together, the posted record supports a description of the reported endpoint and safety counts, not a broad conclusion about efficacy or safety.
The findings also apply to the study population and conduct represented by this trial, not automatically to every setting or group of patients with COVID-19. The registry gives limited detail about participant characteristics and the analysis population. Without those details and a reported comparative analysis, interpretation should remain tied to the exact outcomes and summaries recorded.
13. Why This Trial Matters Statistically
This trial is statistically notable for its time-to-improvement primary outcome. Time-to-event endpoints require more than a comparison of arm-specific medians: interpretation also depends on follow-up, censoring, event counts, and the method used to estimate the event-time distribution. The registry reports the medians and their confidence intervals, but does not provide those analysis details or a direct treatment contrast. That makes the distinction between descriptive summaries and comparative inference especially important.
The record also illustrates why confidence intervals for separate arms should not be mistaken for an interval around a treatment effect. Each posted interval describes uncertainty in its own arm's median. A formal comparison requires an estimate of the contrast and uncertainty calculated for that contrast. Neither a hazard ratio nor another comparative estimate is reported for the primary endpoint.
Another statistical consideration is the relationship between registry enrollment and the outcome entries. Enrollment is listed as 70, while the arm-level outcome entries report 47 and 23 participants. Without a participant flow account or a stated analysis population, readers cannot determine from the record how those numbers relate or how much outcome information was available.
The record names several secondary outcomes but does not report their results or a multiplicity approach. This matters because interpretation across a set of outcomes depends on the intended testing strategy, not simply on which results are available. No detailed statistical analysis plan is reported in the registry record.
These limitations do not invalidate the posted summaries. They define what the summaries can support: a descriptive account of the reported endpoint and safety entries, with substantial aspects of the comparative analysis not reported. That distinction is useful when reading clinical trial registries, where outcome values may be present without the context needed to assess the full inferential analysis.
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 primary endpoint is reported as a median time, but the registry does not identify the estimator used or explain how participants without an observed improvement by Day 28 were handled. It does not report event counts, censoring details, follow-up completeness, or a hazard ratio. These omissions prevent a full assessment of the time-to-event analysis and its assumptions.
The reported confidence intervals apply to each arm's median, not to a treatment contrast. No comparative confidence interval or p-value is reported. The posted summaries therefore do not give a direct measure of the precision of the difference between treatment groups. A comparison should not be reconstructed from the medians or their separate confidence intervals.
The outcome entries list 47 participants for NPC-26 and 23 for NP-26 Placebo, while enrollment is reported as 70. The record does not provide a participant flow account, reasons for any non-inclusion in outcome summaries, or a definition of the analysis population. It also does not report baseline characteristics in the registry record analyzed here, limiting assessment of the groups represented in the outcome summaries.
The registry names secondary outcomes but does not report their results, the planned multiplicity strategy, or an outcome hierarchy. Missing-data procedures, interim analyses, model specifications, and sensitivity analyses are not reported in the registry record. The absence of these details does not establish that they were not considered in the trial; it means they cannot be evaluated from this record.
The safety entries lack detail on event definitions, timing, attribution, and whether participants could have multiple events. The serious-event terms are not linked to an arm in the listed information. Consequently, the counts are descriptive and do not support a causal interpretation or a detailed comparison of safety profiles.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase II/III Study of Sargramostim — NCT04642950.
- Registry record last updated 2024-07-19; status last verified 2021-11.
- Results first posted 2024-07-19.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT04642950 is a completed randomized, placebo-controlled Phase II/III study sponsored by Nobelpharma. It evaluated inhaled sargramostim as add-on treatment to standard treatment for patients with COVID-19, compared with inhaled physiological saline as add-on treatment. The record reports a study start of 2020-12-17, primary completion on 2021-10-25, and enrollment of 70.
The primary endpoint was days to at least a 2-rank improvement on a 7-point ordinal scale through Day 28, including after discharge. The median was 9 days for NPC-26, with a 95% confidence interval of 8 to 9 days, and 8 days for NP-26 Placebo, with a 95% confidence interval of 7 to 10 days. A direct comparative estimate and details of the time-to-event analysis are not reported in the registry record.
Safety entries report serious adverse events, other adverse events, and deaths by arm. The registry names secondary outcomes but does not report their results in the information analyzed. Missing-data handling, analysis populations, and multiplicity procedures are also not reported.