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 Safety and Efficacy of C21 in Subjects With COVID-19 (NCT04452435), a randomized phase 2 study. The primary outcome is Change From Baseline in C-reactive Protein (CRP) After Treatment With C21 200 mg Daily Dose (100 mg b.i.d.).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04452435 |
| Phase | Phase 2 |
| Condition | COVID-19 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 206 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Vicore Pharma AB |
| Results posted | Yes |
2. Clinical Question
Population
Hospitalized subjects with COVID-19 who did not require mechanical invasive or non-invasive ventilation were eligible for the trial described in the registry record. The primary endpoint analysis used the full analysis set: 45 subjects in the C21 group and 46 in the placebo group. The record does not give further eligibility details in the information available for this analysis.
Intervention
The intervention was oral C21, 100 mg twice daily for 7 days, alongside standard of care. The trial was described as a phase 2 investigation of safety and efficacy. The intervention record does not report additional treatment details beyond the dose, route, and duration.
Comparator
The comparator was oral placebo, 100 mg twice daily for 7 days, alongside standard of care. The trial used random allocation and masking. The registry record identifies the masking as triple, while its brief summary describes the trial as double-blind.
Primary question
The primary endpoint asked how C-reactive protein (CRP) changed from baseline to the average of the last two assessments during the 7-day treatment period, Day 1 to Day 8. The statistical comparison was intended to describe the treatment groups’ endpoint results. The registry record does not provide a numerical between-group effect estimate or confidence interval from the ANCOVA analyses.
3. Trial Design
This was a randomized, parallel-group, placebo-controlled phase 2 trial of C21 in hospitalized subjects with COVID-19. The registry record lists triple masking; the brief summary calls the study double-blind. The record does not identify which parties were masked, so the difference in wording cannot be resolved from the registry information.
The treatment groups were C21 plus standard of care and placebo plus standard of care. C21 was given orally at 100 mg twice daily for 7 days, and placebo was given orally at the same schedule and duration. The trial population was described as hospitalized subjects who did not require mechanical invasive or non-invasive ventilation.
The registry lists enrollment of 206. The brief summary describes an intention to enroll approximately 100 subjects, with 50 assigned to each group. The record does not explain the difference between the enrollment figure and the approximate target in the summary, or how those figures relate to the analysis populations. For the primary endpoint, 45 subjects in the C21 group and 46 in the placebo group were included in the full analysis set.
The trial is marked completed. Its start date is 2020-07-21, and its primary completion date is 2020-10-13. These dates and the treatment schedule describe the trial’s conduct, but do not establish how complete outcome follow-up was for individual participants. Further details about allocation procedures, masking implementation, and the statistical analysis plan are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 96 enrolled subjects were screening failures because inclusion criteria 4 was not met. 2 enrolled subjects decided to withdraw from the trial before randomization. 2 subjects died before randomization (pneumonia). The remaining 106 subjects were randomized to trial treatment.
Screening
| Stage | C21 Treatment | Placebo Treatment |
|---|---|---|
| STARTED | 51 | 55 |
| COMPLETED | 51 | 55 |
| NOT COMPLETED | 0 | 0 |
Treatment Period
| Stage | C21 Treatment | Placebo Treatment |
|---|---|---|
| STARTED | 51 | 55 |
| COMPLETED | 45 | 43 |
| NOT COMPLETED | 6 | 12 |
Follow-up
| Stage | C21 Treatment | Placebo Treatment |
|---|---|---|
| STARTED | 45 | 43 |
| COMPLETED | 45 | 42 |
| NOT COMPLETED | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set. A total of 45 subjects in the C21 group and 46 subjects in the placebo group were included in the analysis of the primary endpoint in the FAS. For a number of the excluded subjects, the reason for exclusion from the primary endpoint analysis was that they had no baseline value available.
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 | C21 Treatment | Placebo Treatment | Total |
|---|---|---|---|---|
| Participants analysed | 51 | 55 | 106 | |
| Age, Continuous | years | 54.3 (29 to 68) | 51.1 (22 to 68) | 52.6 (22 to 68) |
| Sex: Female, Male: Female | Participants | 13 | 13 | 26 |
| Sex: Female, Male: Male | Participants | 38 | 42 | 80 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 51 | 55 | 106 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 51 | 55 | 106 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: India | participants | 51 | 55 | 106 |
| Height | cm | 166.1 (132 to 198) | 166.0 (143 to 188) | 166.1 (132 to 198) |
| Weight | kg | 70.1 (46 to 116) | 69.2 (47 to 112) | 69.6 (46 to 116) |
| Body mass index | kg/m^2 | 25.4 (15 to 41) | 25.1 (20 to 34) | 25.2 (15 to 41) |
| Supplemental oxygen use at baseline | Participants | 29 | 32 | 61 |
| CRP value ≤ median | Participants | 24 | 22 | 46 |
| CRP value > median | Participants | 21 | 25 | 46 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in C-reactive Protein (CRP) After Treatment With C21 200 mg Daily Dose (100 mg b.i.d.), measured over Treatment period of 7 days (Day 1 to Day 8).
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 90% Confidence Interval |
| Unit | mg/L |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was change in C-reactive protein (CRP), measured in mg/L. It was defined as the change from baseline to the average of the last two assessments in the treatment period, which ran from Day 1 to Day 8. The registry identifies the reported group statistic as a least-squares mean and gives a 90% confidence interval for each group.
CRP is an inflammatory marker, so measuring its change can describe how the marker behaved during treatment. That makes it a laboratory endpoint, not a direct measure of how a subject felt or functioned. The endpoint’s definition also matters: it uses an average of the last two treatment-period assessments rather than a single final measurement. The registry does not report the timing of those two assessments beyond the stated treatment period.
For this endpoint, a group’s least-squares mean is a model-based summary. In general, such estimates can reflect an adjusted analysis, but the registry record does not specify the covariates used in the ANCOVA or provide the model details. A confidence interval expresses uncertainty around an estimate under the analysis assumptions; it does not show the range of individual subjects’ CRP changes.
The posted group estimates describe the endpoint within each arm. A between-group effect estimate and its confidence interval would be needed to quantify the estimated contrast directly. Those values are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary endpoint estimates were 0.19 for C21 and 0.22 for placebo. Their respective 90% confidence intervals were 0.14 to 0.25 and 0.17 to 0.29. These are group-level least-squares means for the defined CRP change endpoint. The intervals overlap, but overlap between separate group intervals is not itself a formal test of the treatment contrast.
The registry lists ANCOVA as the method for two analyses and reports p-values of =0.489 and =0.088. Both analysis entries are classified as equivalence analyses, but the record does not explain how the two entries differ, identify an equivalence margin, or provide a corresponding between-group estimate and confidence interval. Those missing details limit what can be concluded from the p-values alone. They should not be read as a substitute for an effect estimate or as proof that the groups were equivalent.
For the primary endpoint, the record therefore supports a description of the arm-level estimates and reported analysis entries, but not a precise numerical account of the adjusted difference between groups. The arm confidence intervals show uncertainty around each group estimate; they do not directly state the uncertainty around the contrast. Further interpretation would require the model’s contrast estimate, its interval, and the analysis details.
The registry also reports counts for two secondary outcomes, with unadjusted recalculations of risk differences and confidence intervals. Such recalculations summarize the observed group counts without the adjustment represented by the sponsor’s listed regression analyses. The secondary results are not interchangeable with the primary CRP analysis: they concern different outcomes, use different statistical approaches, and are secondary rather than primary measures.
None of these registry statistics establishes a clinical benefit or lack of benefit. The numerical estimates describe results under the definitions and populations recorded, and their precision depends on the available information. For the primary endpoint, the absence of a reported between-group estimate and interval is a particularly important limit when judging the magnitude and precision of the treatment contrast.
9. Statistical Methods Explained
The primary endpoint is summarized by least-squares means with 90% confidence intervals. The registry lists ANCOVA for the primary analyses, but does not report the model specification, included covariates, missing-data handling within the model, or the contrast estimate. These omissions matter because an analysis method’s name alone does not show exactly how the reported result was obtained.
What a confidence interval describes
General statistical explanation: a confidence interval gives a range of values compatible with the estimate under the model and its assumptions. It describes uncertainty in an estimated quantity; it is not a range containing a specified proportion of individual participants’ values. The primary endpoint intervals apply to the separate arm-level least-squares means. Since a confidence interval for the between-group contrast is not reported, the precision of that contrast cannot be read directly from the arm intervals.
What ANCOVA contributes
General statistical explanation: analysis of covariance (ANCOVA) compares outcomes between groups while accounting for selected covariates. The adjustment can affect the estimated comparison and its uncertainty. The registry identifies ANCOVA as the method but does not state which covariates were included or give enough model detail to reproduce the sponsor’s analysis. The listed p-values are not accompanied by a contrast estimate or confidence interval.
How the binary secondary outcomes are summarized
For two secondary outcomes, the registry gives participant counts by arm and unadjusted recalculations of risk differences. A risk difference expresses the difference between the observed proportions in the two groups, on the probability scale. Its confidence interval describes uncertainty around that estimated difference. The recalculations use the posted summary counts and are not adjusted regression estimates. The registry also lists logistic regression analyses for those outcomes, with p-values but without regression estimates or confidence intervals.
General statistical explanation: a risk-difference interval that includes zero is compatible with no difference as well as with differences in either direction under the calculation’s assumptions. An interval that does not include zero does not, by itself, resolve issues such as multiplicity, bias, or clinical importance. Interpretation should consider the estimated size, uncertainty, analysis plan, and outcome context together.
Why over-dispersion can matter
General statistical explanation: over-dispersion occurs when observed variability is greater than a model assumes. If a model does not account for that extra variation, its standard errors and confidence intervals may be too small, making results appear more precise than warranted. The registry record does not report an over-dispersion assessment for these analyses, so no conclusion about whether it was present or addressed can be drawn.
Planning illustrations are not observed power
The planning illustrations use the observed secondary-outcome effect as a reference and describe hypothetical participants per arm for 80% or 90% power under a two-sided significance level of 0.05, equal allocation, and a normal approximation. For planning for 100% of the observed oxygen-supply effect, the illustration gives 112 participants per arm for 80% power and 149 for 90% power. For planning for 75% of that observed effect, it gives 204 and 272 participants per arm; for 50%, it gives 468 and 626.
For the ventilation outcome, planning for 100% of the observed effect gives 1,520 participants per arm for 80% power and 2,035 for 90% power. Planning for 75% gives 2,899 and 3,881; planning for 50% gives 6,964 and 9,322 participants per arm. These are hypothetical planning illustrations, not observed power and not evidence that the trial had a particular probability of detecting an effect. They are based on the observed effects, so they are sensitive to the uncertainty in those estimates. The registry does not report that these assumptions were used to design the trial.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| ANCOVA | not reported | =0.4891 | |
| ANCOVA | not reported | =0.0881 |
The registry reports two ANCOVA analyses for the primary endpoint, with p-values of =0.489 and =0.088. Both are labeled as equivalence analyses. It does not report the corresponding ANCOVA effect estimates or confidence intervals, explain the distinction between the two analyses, or state the equivalence margin. The p-values therefore give limited information about the size and precision of the primary between-group contrast.
The unadjusted recalculations available for secondary outcomes use arm-level counts and do not reproduce the sponsor’s logistic regression analyses. Their p-values and estimates need not match the sponsor’s adjusted results because the methods differ. The registry does not provide regression estimates or confidence intervals for those secondary analyses.
No discrepancy between sponsor analyses and recalculations is flagged in the registry record. The sponsor’s own analyses remain the relevant reported analyses for their specified models; the summary-statistic recalculations are supplementary descriptions, not replacements. Because no primary endpoint recalculation is reported, there is no recalculated primary contrast to compare with the ANCOVA results.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple primary analysis entries and a range of secondary outcomes, but does not report a multiplicity strategy. It is not stated whether the primary analyses were governed by a prespecified hierarchy, whether secondary outcomes were adjusted for multiple testing, or whether any results were designated exploratory. Without that information, p-values across outcomes should not be treated as if each were the only test conducted.
The primary endpoint analysis used the full analysis set, with 45 subjects in the C21 group and 46 in the placebo group. The registry description says that some subjects were excluded from the primary endpoint analysis because they had no baseline value. The complete number of exclusions and the full reasons are not reported in the registry record. The record also does not describe imputation, sensitivity analyses, or assumptions about missing data.
Analysis populations vary across the recorded outcomes. The binary secondary outcomes list 51 subjects in the C21 group and 55 in the placebo group. Safety records also give group-specific populations and a no-treatment group before randomization. The registry does not give a complete account of how subjects moved among these populations or why outcome-specific denominators differ.
The registry lists enrollment of 206 while the trial summary describes approximately 100 subjects planned for randomization. The record does not explain this difference or provide enough detail to reconcile it. This uncertainty should not be resolved by assuming that all enrolled subjects were randomized or included in every analysis. More detailed participant flow, missing-data accounting, and analysis-plan information are not reported in the registry record.
12. 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 |
|---|---|---|---|
| C21 Treatment | 1 | 51 | 2.0% |
| Placebo Treatment | 3 | 55 | 5.5% |
| No Treatment (Before Randomization) | 2 | 100 | 2.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| C21 Treatment | 1 of 51 |
| Placebo Treatment | 3 of 55 |
| No Treatment (Before Randomization) | 2 of 100 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| C21 Treatment | 30 of 51 |
| Placebo Treatment | 36 of 55 |
| No Treatment (Before Randomization) | 0 of 100 |
Most frequent serious adverse event terms
| Event term | Organ system | C21 Treatment | Placebo Treatment | No Treatment (Before Randomization) |
|---|---|---|---|---|
| COVID-19 pneumonia | Infections and infestations | 0 of 51 | 2 of 55 | 2 of 100 |
| Cardio-respiratory arrest | Cardiac disorders | 1 of 51 | 1 of 55 | 0 of 100 |
Most frequent non-serious adverse event terms
| Event term | Organ system | C21 Treatment | Placebo Treatment | No Treatment (Before Randomization) |
|---|---|---|---|---|
| Hyperglycaemia | Metabolism and nutrition disorders | 11 of 51 | 4 of 55 | n/a of 100 |
| Aspartate aminotransferase increased | Investigations | 6 of 51 | 3 of 55 | n/a of 100 |
| Blood glucose increased | Investigations | 5 of 51 | 3 of 55 | n/a of 100 |
| Interleukin level increased | Investigations | 4 of 51 | 4 of 55 | n/a of 100 |
| Alanine aminotransferase increased | Investigations | 3 of 51 | 4 of 55 | n/a of 100 |
| Serum ferritin increased | Investigations | 5 of 51 | 2 of 55 | n/a of 100 |
| Hyponatraemia | Metabolism and nutrition disorders | 2 of 51 | 3 of 55 | n/a of 100 |
| Alpha tumour necrosis factor increased | Investigations | 1 of 51 | 3 of 55 | n/a of 100 |
| Carbohydrate antigen 125 increased | Investigations | 0 of 51 | 4 of 55 | n/a of 100 |
| Lymphocyte count decreased | Investigations | 1 of 51 | 3 of 55 | n/a of 100 |
Serious events with the highest arm-level rate: covid-19 pneumonia (3.6%), cardio-respiratory arrest (2.0%).
The safety record lists serious adverse events for 1 of 51 subjects in the C21 group, 3 of 55 in the placebo group, and 2 of 100 in the no-treatment group before randomization. It also reports deaths of 1, 3, and 2 in those respective groups. These counts describe the registry’s recorded groups; they do not establish that treatment caused or prevented an event.
The record identifies COVID-19 pneumonia at 3.6% and cardio-respiratory arrest at 2.0% among the top serious adverse event terms. It does not assign those term percentages to a particular treatment arm in the information recorded. Other adverse events were recorded for 30 of 51 subjects receiving C21, 36 of 55 receiving placebo, and 0 of 100 in the pre-randomization no-treatment group.
These figures should be interpreted descriptively. Event counts do not convey timing, severity beyond the serious-event classification, relatedness to treatment, or follow-up completeness. The pre-randomization group is not a randomized treatment comparator. The registry record does not provide enough detail to make causal comparisons from these counts alone.
13. What the Result Does, and Does Not, Mean
The results describe a short phase 2 trial in hospitalized subjects with COVID-19. The primary endpoint measured change in CRP over the treatment period, using the average of the last two assessments. The registry reports arm-level least-squares means and confidence intervals, as well as ANCOVA p-values, but not the numerical between-group estimate and its interval. That missing contrast limits assessment of the magnitude and precision of the primary comparison.
The statistical results do not, by themselves, establish whether the treatment made a clinically important difference. A laboratory marker is one kind of outcome, and its interpretation is not equivalent to a direct assessment of symptoms, function, or longer-term health. The registry does not report a threshold for a clinically meaningful CRP change or a link between the observed marker change and later outcomes.
The secondary outcomes provide additional descriptions but have incomplete numerical reporting and raise questions about multiplicity and analysis populations. Their results should not be treated as independent confirmation of the primary result. Likewise, safety counts are descriptive and do not establish causation.
The findings are limited to the participants, outcome definitions, treatment schedule, and analysis populations recorded. The registry does not report detailed information about missing-data methods, the primary model specification, or a multiplicity plan. These gaps make it difficult to judge how sensitive the reported results may be to analytical choices. The results therefore support a careful account of what was measured and reported, not a broad claim about effects in other populations or settings.
14. Why This Trial Matters Statistically
This trial illustrates why a group-level estimate and a between-group contrast are not interchangeable. The registry reports separate least-squares means for the two arms, but without the primary contrast and its confidence interval, the size and precision of the treatment comparison remain difficult to characterize. A p-value alone cannot fill that gap: it does not show the estimated magnitude or the range of plausible effects.
It also highlights the importance of keeping analysis populations clear. The primary endpoint used a full analysis set of 45 and 46 subjects, while the binary secondary outcomes list 51 and 55. The registry notes missing baseline values as a reason for some primary exclusions but does not give a complete participant flow or missing-data account. Differences in denominators are therefore not just bookkeeping; they affect which participants and observations contribute to each result.
Finally, this record shows why secondary analyses require context. Several outcomes are registered, but detailed numerical comparisons are not uniformly available, and a multiplicity strategy is not reported. Unadjusted recalculations can help describe counts, while remaining distinct from the sponsor’s regression analyses. Planning illustrations based on observed effects can also inform hypothetical study sizing, but they are not the trial’s original design rationale and do not represent observed power.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
Several trial-specific limitations constrain interpretation. The primary endpoint analysis includes 45 subjects in the C21 group and 46 in the placebo group, while the registry lists enrollment of 206 and the summary describes approximately 100 subjects intended for randomization. The relationship among these figures is not explained. The primary description mentions missing baseline values as a reason for some exclusions, but does not give a complete accounting of exclusions or other missing data.
The primary arm-level estimates are reported with 90% confidence intervals, but the ANCOVA entries do not include a between-group estimate or its interval. The registry also does not explain the two primary analysis entries or report an equivalence margin. Model covariates, sensitivity analyses, and the approach to missing outcomes are not reported in the registry record.
Only selected secondary outcomes have detailed counts and unadjusted recalculations in the recorded information. Other endpoint values may be missing or not estimable for a two-arm comparison. The registry does not report how multiplicity was handled, so the inferential status of multiple secondary tests is uncertain.
The treatment period lasted 7 days, and the primary endpoint summarizes CRP over that period. Longer-term outcomes and follow-up details are not reported in the registry record. Safety counts are descriptive, and the pre-randomization no-treatment group cannot serve as a randomized treatment comparison. The registry also differs in its use of double-blind and triple-masking terminology, without clarifying the masking arrangements.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Safety and Efficacy of C21 in Subjects With COVID-19 — NCT04452435.
- Registry record last updated 2021-06-23; status last verified 2021-06.
- Results first posted 2021-04-30.
- 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.
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19. Record Summary
NCT04452435 is a completed randomized, parallel-group phase 2 trial of C21 and placebo in hospitalized subjects with COVID-19 who did not require mechanical invasive or non-invasive ventilation. Treatment was oral C21 100 mg twice daily or placebo twice daily for 7 days, alongside standard of care. The primary endpoint was change in CRP from baseline to the average of the last two treatment-period assessments.
The primary full analysis set included 45 subjects in the C21 group and 46 in the placebo group. The registry reports arm-level least-squares means with 90% confidence intervals and two ANCOVA p-values, but no numerical between-group estimate or interval. Secondary outcomes and safety counts provide additional descriptive information, with limits from incomplete reporting, differing analysis populations, and unreported multiplicity and missing-data methods.