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 First-In-Human Study To Evaluate Safety, Tolerability, And Pharmacokinetics Following Single Ascending And Multiple Ascending Doses of PF-07304814 In Hospitalized Participants With COVID-19. (NCT04535167), a randomized phase 1 study. The primary outcome is Number of Participants With TEAEs, SAEs, and Severe TEAEs - Part 1: SAD.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04535167 |
| Phase | Phase 1 |
| Condition | Viral Disease |
| Allocation | Randomized |
| Design model | Factorial |
| Masking | Triple |
| Enrollment | 26 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Hospitalized participants with COVID-19, described in the brief summary as patients hospitalized with SARS-CoV-2 virus infection. The primary endpoint population for Part 1 included participants randomly assigned to study intervention who took at least 1 dose for that part; analysis was according to the product actually received.
Intervention
PF-07304814, administered by intravenous infusion. The study had a single ascending dose part with 24-hour infusions and a multiple ascending dose part with 120-hour infusions. The adverse-event groups identify PF-07304814 infusions at 250 mg and 500 mg in both parts.
Comparator
Placebo, with placebo groups identified for Part 1 and Part 2. The registry describes the study as placebo-controlled. The record does not report additional details about how the placebo was matched to the active infusions.
Primary question
How many participants experienced treatment-emergent adverse events, serious adverse events and severe treatment-emergent adverse events during Part 1, from Day 1 to 37 days? Pharmacokinetic measures for the prodrug PF-07304814 and active moiety PF-00835231 were also listed as secondary outcomes. The primary endpoint is a safety question, not an assessment of clinical efficacy.
The study was designed as an early evaluation of safety, tolerability and pharmacokinetics in hospitalized participants with COVID-19. Its registry title describes a first-in-human study, but the record does not provide results that would establish whether PF-07304814 improves COVID-19 outcomes. The primary endpoint counts participants in specified adverse-event categories, while the secondary outcomes concern drug concentrations and pharmacokinetic parameters.
The registry lists 26 participants enrolled overall. It does not give a single primary comparison estimate, confidence interval or hypothesis test for the endpoint. The posted adverse-event figures cover groups from both study parts, whereas the named primary outcome is specifically for Part 1. Consequently, the group counts should be read as descriptive safety data within the listed groups, rather than as a definitive comparison of PF-07304814 with placebo.
3. Trial Design
The registry describes a Phase 1b, two-part, randomized, double-blind, placebo-controlled study with sponsor-open masking and a factorial model. The phase field identifies Phase 1. The study evaluated intravenous PF-07304814 in hospitalized participants with COVID-19. Its status is completed; the recorded start date is 2020-09-09 and the primary completion date is 2021-06-07.
Part 1 used single ascending doses (SAD) delivered as 24-hour continuous infusions. The listed cohorts were Cohorts 1–5, with PF-07304814 and placebo groups. Part 2 used multiple ascending doses (MAD) delivered as 120-hour continuous infusions, with Cohorts 6–9 and PF-07304814 and placebo groups. Adverse-event group descriptions identify 250 mg and 500 mg PF-07304814 infusions in Part 1 and Part 2, as well as placebo groups. The registry does not report the allocation sequence or the details of dose escalation.
Enrollment was 26. Although randomization, triple masking and a sponsor-open study are recorded, the registry record does not explain which participants or study personnel were masked, or how sponsor access was handled. It also does not report the number assigned to each cohort in the design description. The primary outcome concerns Part 1 safety through Day 1 to 37 days. Secondary outcomes include plasma concentrations at the end of infusion and pharmacokinetic parameters for PF-07304814, the prodrug, and PF-00835231, the active moiety.
The record describes participants analyzed according to the product they actually received for the relevant part, among those randomly assigned and taking at least 1 dose. It does not report a separate account of protocol deviations or withdrawals. Further details of the intended statistical design, including a formal sample-size justification and planned inferential comparisons, 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: A total of 26 hospitalized participants with COVID-19 were enrolled in this study. 25 participants were randomized to receive single ascending (24-hour, part 1) or multiple ascending (120-hour, part 2) intravenous infusions of PF-07304814 or placebo. One participant was not treated and discontinued from study due to being incorrectly randomized. All reported data are on 25 participants who were randomized and received at least 1 dose of PF-07304814 or placebo (referred to as "enrolled" herein).
Only the first 6 of 7 groups are shown.
Treatment
| Stage | Part 1: PF-07304814 500 mg 24-hours Continuous Infusion | Part 1: PF-07304814 250 mg 24-hours Continuous Infusion | Part 1: 500 mg Placebo 24-hours Continuous Infusion | Part 1: 250 mg Placebo 24-hours Continuous Infusion | Part 2: PF-07304814 500 mg 120-hours Continuous Infusion | Part 2: PF-07304814 250 mg 120-hours Continuous Infusion |
|---|---|---|---|---|---|---|
| STARTED | 2 | 2 | 2 | 2 | 6 | 7 |
| COMPLETED | 2 | 2 | 2 | 2 | 6 | 7 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Reasons for not completing this period:
| Reason | Part 1: PF-07304814 500 mg 24-hours Continuous Infusion | Part 1: PF-07304814 250 mg 24-hours Continuous Infusion | Part 1: 500 mg Placebo 24-hours Continuous Infusion | Part 1: 250 mg Placebo 24-hours Continuous Infusion | Part 2: PF-07304814 500 mg 120-hours Continuous Infusion | Part 2: PF-07304814 250 mg 120-hours Continuous Infusion |
|---|---|---|---|---|---|---|
| Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 |
Follow-Up
| Stage | Part 1: PF-07304814 500 mg 24-hours Continuous Infusion | Part 1: PF-07304814 250 mg 24-hours Continuous Infusion | Part 1: 500 mg Placebo 24-hours Continuous Infusion | Part 1: 250 mg Placebo 24-hours Continuous Infusion | Part 2: PF-07304814 500 mg 120-hours Continuous Infusion | Part 2: PF-07304814 250 mg 120-hours Continuous Infusion |
|---|---|---|---|---|---|---|
| STARTED | 2 | 2 | 2 | 2 | 6 | 7 |
| COMPLETED | 2 | 2 | 2 | 1 | 6 | 7 |
| NOT COMPLETED | 0 | 0 | 0 | 1 | 0 | 0 |
Reasons for not completing this period:
| Reason | Part 1: PF-07304814 500 mg 24-hours Continuous Infusion | Part 1: PF-07304814 250 mg 24-hours Continuous Infusion | Part 1: 500 mg Placebo 24-hours Continuous Infusion | Part 1: 250 mg Placebo 24-hours Continuous Infusion | Part 2: PF-07304814 500 mg 120-hours Continuous Infusion | Part 2: PF-07304814 250 mg 120-hours Continuous Infusion |
|---|---|---|---|---|---|---|
| Death | 0 | 0 | 0 | 0 | 0 | 0 |
| Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention for the given part of the study (Part 1: SAD). Participants were analyzed according to the product they actually received.
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.
Only the first 6 of 8 groups are shown.
| Characteristic | Unit | Part 1: PF-07304814 500 mg 24-hours Continuous Infusion | Part 1: PF-07304814 250 mg 24-hours Continuous Infusion | Part 1: 500 mg Placebo 24-hours Continuous Infusion | Part 1: 250 mg Placebo 24-hours Continuous Infusion | Part 2: PF-07304814 500 mg 120-hours Continuous Infusion | Part 2: PF-07304814 250 mg 120-hours Continuous Infusion |
|---|---|---|---|---|---|---|---|
| Participants analysed | 2 | 2 | 2 | 2 | 6 | 7 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 2 | 2 | 1 | 5 | 5 |
| Age, Categorical: >=65 years | Participants | 1 | 0 | 0 | 1 | 1 | 2 |
| Sex: Female, Male: Female | Participants | 1 | 0 | 1 | 1 | 2 | 1 |
| Sex: Female, Male: Male | Participants | 1 | 2 | 1 | 1 | 4 | 6 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 1 | 0 | 2 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 | 2 | 1 | 2 | 4 | 5 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 0 | 1 | 0 |
| Race (NIH/OMB): White | Participants | 2 | 1 | 1 | 2 | 5 | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 | 0 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With TEAEs, SAEs, and Severe TEAEs - Part 1: SAD, measured over Day 1 to 37 days.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is titled “Number of Participants With TEAEs, SAEs, and Severe TEAEs - Part 1: SAD.” It measures participant counts in three safety categories: treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and severe TEAEs. The stated timeframe is Day 1 to 37 days. The registry defines an adverse event as an untoward medical occurrence temporally associated with study intervention, whether or not it is considered related to that intervention. A TEAE is an event that starts during the effective duration of treatment.
An SAE is defined by specified consequences, including death, a life-threatening event, hospitalization or prolonged hospitalization, persistent disability, a congenital anomaly or birth defect, or an important medical event. Seriousness and severity describe different features: seriousness is based on the event’s consequences or regulatory criteria, while severity concerns how intense an event is. The record’s endpoint names both SAEs and severe TEAEs, so those categories should not be treated as interchangeable.
Counting participants with events is a direct way to describe safety experience in an early-phase study. It can identify whether events occurred in the observed groups and provide context for further evaluation. A count alone does not establish that an event was caused by the intervention, nor does it quantify comparative risk with precision. The registry record does not provide a single combined numerical result for all three endpoint categories, and the separate count of participants with severe TEAEs is not reported in the posted group figures.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies safety, tolerability and pharmacokinetics as the study’s aims. The primary outcome is a participant count for TEAEs, SAEs and severe TEAEs in Part 1, rather than a clinical efficacy endpoint. The posted results give adverse-event counts by infusion group across both Part 1 and Part 2. They do not provide a single treatment-effect estimate or statistical comparison for the primary endpoint. The registry lists 25 outcome measures and no analyses.
In Part 1, the 500 mg PF-07304814 group had 1 serious adverse event among 2 participants at risk and 1 other adverse event among 2 at risk. The 250 mg PF-07304814 group had 0 serious adverse events among 2 at risk and 1 other adverse event among 2 at risk. In the 500 mg placebo group, 1 serious adverse event affected 2 participants at risk and 2 had other adverse events; the 250 mg placebo group also had 1 serious adverse event among 2 at risk and 2 with other adverse events. No deaths are listed for these Part 1 groups.
Part 2 figures show 1 serious adverse event among 6 participants at risk and 2 with other adverse events among 6 in the 500 mg PF-07304814 group. For 250 mg PF-07304814, 2 serious adverse events and 3 other adverse events were reported among 7 participants at risk. In the Part 2 placebo group, 1 serious adverse event and 3 other adverse events were reported among 4 participants at risk; 1 death is listed for that group. These counts are not adjusted comparisons and should not be read as evidence that an intervention caused or prevented an event.
The groups are small, so each participant contributes substantially to the observed counts. A difference in the displayed counts would not by itself establish a reliable difference in underlying event rates. No confidence intervals or inferential tests for these group counts are reported in the registry record. The top serious-event terms listed include COVID-19 pneumonia and subclavian vein thrombosis at 50.0% each, followed by hypoxia and pulmonary embolism at 25.0% each, and pneumonia and acute respiratory distress syndrome at 14.3% each. The record does not specify the denominator or counting convention underlying those term percentages.
Pharmacokinetic outcomes were also listed, including concentration at 24 hours in Part 1, concentration at 120 hours in Part 2, maximum observed concentration, half-life and steady-state concentration. Numerical results for those outcomes are not reported in the registry record for this analysis. The registry results therefore describe the study’s scope and selected adverse-event counts, but do not support a complete assessment of pharmacokinetics or a formal efficacy conclusion.
9. Statistical Methods Explained
The registry frames the primary endpoint as a count of participants with specified adverse-event categories. This is a binary-outcome structure at the participant level: for a particular event category, each participant either is or is not counted as having experienced an event within the defined observation period. The registry also gives the numbers at risk for each listed infusion group. These counts describe the observed groups; they are not, on their own, estimates of a causal treatment effect.
What does a participant count convey?
A count answers how many participants met the endpoint definition in the group being described. It is different from a count of all individual event episodes: one participant can experience more than one event, while a participant-level endpoint generally counts that participant once within a category. The registry’s primary outcome is explicitly worded as the number of participants, but the posted figures do not provide a complete separate result for every primary category. In particular, the reported group values distinguish serious adverse events and other adverse events; a distinct severe TEAE result is not reported.
When groups are small, counts can change noticeably with the experience of a single participant. General statistical principle: uncertainty around an estimated event proportion is often substantial when the denominator is small. A confidence interval, when reported, would express a range of values compatible with the data and the chosen method; it would not guarantee that the true value lies in that range. No confidence intervals for the adverse-event counts are reported in the registry record, so precision should not be inferred from the counts alone.
Why separate seriousness from severity?
The registry defines SAEs by outcomes or clinical significance, such as hospitalization or a life-threatening event. A severe TEAE is identified by intensity, which is not necessarily the same concept as seriousness. An event may be intense without meeting an SAE criterion, and an event can meet a seriousness criterion without being described as severe. General statistical interpretation therefore requires keeping the endpoint categories distinct. The posted descriptions do not allow the SAE counts to stand in for severe TEAE counts.
What do the pharmacokinetic outcomes measure?
The secondary outcomes concern concentrations of PF-07304814, the prodrug, and PF-00835231, the active moiety. The registry lists measurements at the end of the 24-hour infusion for Part 1 and at the end of the 120-hour infusion for Part 2, along with maximum observed concentration, half-life and steady-state concentration. In general, concentration-time measures describe drug exposure over time, while parameters such as maximum concentration and half-life summarize aspects of that profile. The numerical pharmacokinetic results are not reported in the record details, so no exposure pattern or dose relationship can be characterized.
What can a comparison establish?
A comparison of randomized groups can help distinguish observed differences from differences caused by participant selection, but precision depends on the amount of information and the analysis plan. Here, randomization and placebo control are recorded, but the registry does not give a primary comparison estimate, confidence interval, or test result. The allocation and masking details are limited; the record labels the design triple-masked and sponsor-open without specifying who remained masked. No adjusted or unadjusted inferential analysis of the primary outcome is listed.
General statistical principle: over-dispersion occurs when observed variation exceeds what a chosen statistical model expects. It matters when a model’s uncertainty estimates rely on an assumption of lower variation, because standard errors and intervals may then be too narrow. The registry does not report a dispersion measure or model-based analysis for this count endpoint, so over-dispersion cannot be assessed from the recorded group counts alone.
How should planning calculations be read?
The sample-size assumptions describe planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations are hypothetical planning scenarios, not evidence about the trial’s actual power and not observed results. For non-time-to-event outcomes, the stated convention is participants per arm; time-to-event calculations use total events. The record does not report the trial’s own sample-size justification or establish that these planning assumptions were used to design the study.
The primary endpoint has several categories or time points and is not reduced to one comparison in the available analysis. This is consequential: the registry’s endpoint label cannot be condensed into one treatment effect without choosing an outcome definition and comparison that the record does not specify. The analysis should therefore remain descriptive and limited to the categories, groups and counts that are explicitly reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 25 outcome measures, including the primary safety outcome and secondary pharmacokinetic outcomes. It records no analyses. A multiplicity strategy—how to interpret statistical evidence when several outcomes or comparisons are assessed—is not reported in the registry record. Without a reported plan, it is not possible to determine whether tests were ordered, adjusted or treated as exploratory. Because the primary endpoint includes several categories or time points, it is also not reduced to one comparison in the posted analysis.
Missing-data methods are not reported in the registry record. The record does not explain how participants with incomplete follow-up, unavailable laboratory or pharmacokinetic measurements, or missing endpoint assessments were handled. It also does not report the extent of missingness for these outcomes. The stated primary population comprises participants randomly assigned to intervention who took at least 1 dose for the relevant study part, with participants analyzed according to the product they actually received. This description does not establish how other analysis populations were defined or how deviations from assigned treatment were addressed.
These omissions limit interpretation of the reported counts and any unreported outcomes. They do not demonstrate that missing observations or multiplicity affected the results; rather, the information needed to assess those issues is not reported in the registry record. The results should not be treated as a prespecified, multiplicity-controlled hypothesis test when no analyses or adjustment plan are recorded.
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 |
|---|---|---|---|
| Part 1: PF-07304814 500 mg 24-hours Continuous Infusion | 1 | 2 | 50.0% |
| Part 1: PF-07304814 250 mg 24-hours Continuous Infusion | 0 | 2 | 0.0% |
| Part 1: 500 mg Placebo 24-hours Continuous Infusion | 1 | 2 | 50.0% |
| Part 1: 250 mg Placebo 24-hours Continuous Infusion | 1 | 2 | 50.0% |
| Part 2: PF-07304814 500 mg 120-hours Continuous Infusion | 1 | 6 | 16.7% |
| Part 2: PF-07304814 250 mg 120-hours Continuous Infusion | 2 | 7 | 28.6% |
| Part 2: Placebo 120-hours Continuous Infusion | 1 | 4 | 25.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Part 1: PF-07304814 500 mg 24-hours Continuous Infusion | 0 of 2 |
| Part 1: PF-07304814 250 mg 24-hours Continuous Infusion | 0 of 2 |
| Part 1: 500 mg Placebo 24-hours Continuous Infusion | 0 of 2 |
| Part 1: 250 mg Placebo 24-hours Continuous Infusion | 0 of 2 |
| Part 2: PF-07304814 500 mg 120-hours Continuous Infusion | 0 of 6 |
| Part 2: PF-07304814 250 mg 120-hours Continuous Infusion | 0 of 7 |
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 |
|---|---|
| Part 1: PF-07304814 500 mg 24-hours Continuous Infusion | 1 of 2 |
| Part 1: PF-07304814 250 mg 24-hours Continuous Infusion | 1 of 2 |
| Part 1: 500 mg Placebo 24-hours Continuous Infusion | 2 of 2 |
| Part 1: 250 mg Placebo 24-hours Continuous Infusion | 2 of 2 |
| Part 2: PF-07304814 500 mg 120-hours Continuous Infusion | 2 of 6 |
| Part 2: PF-07304814 250 mg 120-hours Continuous Infusion | 3 of 7 |
Most frequent serious adverse event terms
| Event term | Organ system | Part 1: PF-07304814 500 mg 24-hours Continuous Infusion | Part 1: PF-07304814 250 mg 24-hours Continuous Infusion | Part 1: 500 mg Placebo 24-hours Continuous Infusion | Part 1: 250 mg Placebo 24-hours Continuous Infusion | Part 2: PF-07304814 500 mg 120-hours Continuous Infusion | Part 2: PF-07304814 250 mg 120-hours Continuous Infusion |
|---|---|---|---|---|---|---|---|
| Subclavian vein thrombosis | Vascular disorders | 1 of 2 | 0 of 2 | 1 of 2 | 0 of 2 | 0 of 6 | 0 of 7 |
| Pneumonia | Infections and infestations | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 6 | 1 of 7 |
| COVID-19 pneumonia | Infections and infestations | 0 of 2 | 0 of 2 | 0 of 2 | 1 of 2 | 0 of 6 | 0 of 7 |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 6 | 1 of 7 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 6 | 1 of 7 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 2 | 1 of 6 | 0 of 7 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 6 | 0 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Part 1: PF-07304814 500 mg 24-hours Continuous Infusion | Part 1: PF-07304814 250 mg 24-hours Continuous Infusion | Part 1: 500 mg Placebo 24-hours Continuous Infusion | Part 1: 250 mg Placebo 24-hours Continuous Infusion | Part 2: PF-07304814 500 mg 120-hours Continuous Infusion | Part 2: PF-07304814 250 mg 120-hours Continuous Infusion |
|---|---|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 1 of 2 | 0 of 2 | 1 of 2 | 0 of 2 | 0 of 6 | 0 of 7 |
| Coagulopathy | Blood and lymphatic system disorders | 0 of 2 | 1 of 2 | 0 of 2 | 0 of 2 | 0 of 6 | 0 of 7 |
| Thrombocytopenia | Blood and lymphatic system disorders | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 6 | 1 of 7 |
| Tachycardia | Cardiac disorders | 0 of 2 | 0 of 2 | 1 of 2 | 0 of 2 | 0 of 6 | 0 of 7 |
| Bradycardia | Cardiac disorders | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 6 | 1 of 7 |
| Tympanic membrane perforation | Ear and labyrinth disorders | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 6 | 1 of 7 |
| Abdominal pain | Gastrointestinal disorders | 0 of 2 | 0 of 2 | 1 of 2 | 0 of 2 | 0 of 6 | 0 of 7 |
| Abdominal pain upper | Gastrointestinal disorders | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 2 | 0 of 6 | 1 of 7 |
| Dyspepsia | Gastrointestinal disorders | 0 of 2 | 0 of 2 | 0 of 2 | 1 of 2 | 0 of 6 | 0 of 7 |
| Oedema | General disorders | 0 of 2 | 0 of 2 | 0 of 2 | 1 of 2 | 0 of 6 | 0 of 7 |
Serious events with the highest arm-level rate: covid-19 pneumonia (50.0%), subclavian vein thrombosis (50.0%), hypoxia (25.0%), pulmonary embolism (25.0%), pneumonia (14.3%).
The adverse-event groups report participants at risk, participants affected by serious adverse events, participants with other adverse events, and deaths. In Part 1, each listed group has 2 participants at risk. Serious-event counts are 1 for the PF-07304814 500 mg group, 0 for the PF-07304814 250 mg group, and 1 in each placebo group. Other adverse-event counts are 1, 1, 2 and 2 in those respective groups. No deaths are listed in Part 1.
For Part 2, the 500 mg PF-07304814 group lists 1 serious and 2 other adverse events among 6 at risk. The 250 mg PF-07304814 group lists 2 serious and 3 other adverse events among 7 at risk. The placebo group lists 1 serious and 3 other adverse events among 4 at risk, and 1 death. These are participant counts, not a statistical comparison. The registry does not report whether the death was considered related to study intervention.
The serious-event terms include COVID-19 pneumonia and subclavian vein thrombosis at 50.0% each; hypoxia and pulmonary embolism at 25.0% each; and pneumonia and acute respiratory distress syndrome at 14.3% each. The denominator and counting method for these percentages are not reported in the registry record. SAEs should not be equated with severe TEAEs, and an event’s occurrence does not by itself establish causation by the study intervention.
12. What the Result Does, and Does Not, Mean
The posted results give a descriptive view of adverse events observed in small groups receiving PF-07304814 or placebo during the study’s single- and multiple-infusion parts. They also show that the registry intended to evaluate pharmacokinetic measures for the prodrug and active moiety. The design and endpoint are consistent with an early-phase safety and pharmacokinetic evaluation, rather than a trial whose primary question is whether treatment changes a clinical outcome of COVID-19.
The counts do not establish that PF-07304814 caused or prevented any reported adverse event. Participants were hospitalized with COVID-19, and the registry defines adverse events by their temporal association with study intervention, whether or not they were considered related. The record does not report event-level causal assessments for the listed groups. The one death recorded in the Part 2 placebo group cannot, from this information alone, be attributed to the intervention or used to compare mortality between groups.
The counts also do not demonstrate that the groups have equivalent safety profiles. Small group sizes, lack of reported confidence intervals and absence of a listed inferential analysis mean that the precision of between-group differences cannot be evaluated. The record does not report a separate severe TEAE result, despite naming severe TEAEs in the primary endpoint. Nor are numerical pharmacokinetic findings available for interpretation.
Accordingly, the most defensible reading is limited: adverse events and serious adverse events were recorded in the groups, with the particular counts stated in the registry, and the study was designed to evaluate safety, tolerability and pharmacokinetics. No conclusion about clinical benefit or lack of benefit follows from these safety counts. No general conclusion about risks in other populations, doses or settings follows from a study of this size and design. Further interpretation would require complete outcome results, analysis details and precision estimates, none of which are reported in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates a central statistical feature of early-phase clinical research: the main information sought may concern safety and drug exposure rather than efficacy. The primary outcome counts participants with TEAEs, SAEs and severe TEAEs, and secondary outcomes address concentrations and pharmacokinetic parameters. Those aims call for clear definitions and careful separation of outcome categories. In particular, SAE status and event severity are not interchangeable.
The record also illustrates why group denominators matter. The adverse-event counts sit alongside small numbers at risk, so each participant’s experience is a substantial part of the observed group result. Descriptive counts are useful for documenting what occurred, but without precision estimates or a reported comparison they cannot support strong conclusions about differences between interventions.
Another statistical issue is the structure of the endpoint and outcome set. The registry lists 25 outcome measures, but no analyses, and the primary endpoint covers several categories or time points rather than one comparison. Multiplicity and analysis decisions are therefore important for interpretation, yet their planned handling is not reported. This makes transparent reporting of definitions, analysis populations, missing data and uncertainty especially valuable.
Finally, the record distinguishes study design features from analysis evidence. Randomization, placebo control and masking are recorded, but the available results do not include a treatment-effect estimate or a statistical test. These features alone do not supply the missing evidence. The trial remains statistically informative as an example of how early-phase safety and pharmacokinetic questions are framed, while also showing why observed counts must be interpreted within their scope and precision.
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 registry record contains limited detail about the allocation process, dose escalation, cohort assignment and masking roles. Although it identifies randomization, triple masking and sponsor-open status, it does not explain the operational meaning of those labels. The record also does not give the number assigned to each cohort in its design description.
The primary endpoint is broader than the adverse-event figures available for interpretation. It names TEAEs, SAEs and severe TEAEs, but the group figures distinguish serious and other adverse events and do not provide a separate severe TEAE result. The timeframe for the endpoint is stated as Day 1 to 37 days, but the posted group data do not supply more detail about follow-up completeness or event timing.
The registry lists adverse-event counts in small groups and does not report confidence intervals, hypothesis tests or a single primary comparison. The available record also does not report detailed event-level causality assessments, missing-data handling, multiplicity control, protocol deviations or a statistical analysis plan. Although pharmacokinetic outcomes are named, their numerical results are not included in the record details used for this interpretation.
The serious-event term percentages are reported, but their denominator and counting convention are not described. The death listed in the Part 2 placebo group has no reported attribution to study intervention. These gaps prevent a more detailed assessment of event rates, treatment contrasts, precision or causal interpretation. They are limitations of what is reported in the registry record, not proof that the underlying study did not collect or analyze additional information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: First-In-Human Study To Evaluate Safety, Tolerability, And Pharmacokinetics Following Single Ascending And Multiple Ascending Doses of PF-07304814 In Hospitalized Participants With COVID-19. — NCT04535167.
- Registry record last updated 2023-05-03; status last verified 2023-04.
- Results first posted 2023-05-03.
- 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.
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18. Record Summary
NCT04535167 is a completed Phase 1b, two-part, randomized, placebo-controlled study of intravenous PF-07304814 in hospitalized participants with COVID-19. Part 1 evaluated single ascending 24-hour infusions; Part 2 evaluated multiple ascending 120-hour infusions. Enrollment was 26, and the recorded dates are 2020-09-09 for study start and 2021-06-07 for primary completion.
The primary outcome was the number of participants with TEAEs, SAEs and severe TEAEs in Part 1 over Day 1 to 37 days. Secondary outcomes addressed plasma concentrations and pharmacokinetic parameters for PF-07304814 and PF-00835231. The registry lists adverse-event counts across groups in both parts but no statistical analyses. It does not report a single primary comparison, confidence intervals, missing-data methods, multiplicity handling or numerical pharmacokinetic results. The posted information supports descriptive reading of the recorded safety counts, not a conclusion about clinical efficacy or causal effects.