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 Efficacy, Safety and Tolerability of AG013 in Oral Mucositis Compared to Placebo When Administered Three Times Per Day (NCT03234465), a randomized phase 2 study. The primary outcome is Efficacy of AG013 Compared to Placebo for Reducing OM as Measured by Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03234465 |
| Phase | Phase 2 |
| Condition | Oral Mucositis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 200 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Oragenics, Inc. |
| Results posted | Yes |
2. Clinical Question
The clinical question was whether topical AG013, used during chemoradiation for head and neck cancer, changed the duration of severe oral mucositis compared with a placebo mouth rinse. Severe oral mucositis was defined for the primary outcome as World Health Organization (WHO) Grades 3 or 4, and duration was measured in days. The registry record describes other planned assessments, including time to development and overall incidence of oral mucositis, patient-reported symptoms, analgesic use, radiation dose before onset, biomarkers, and pharmacokinetic measures in a subset. However, the registry record does not report results for those assessments.
Population
People with cancers of the head and neck receiving concomitant chemoradiation therapy. The primary outcome description does not further specify an analysis population.
Intervention
AG013 mouth rinse, administered three times per day from the start of radiotherapy until 2 weeks following its completion. The active treatment phase was described as lasting 7 to 9 weeks, depending on radiotherapy duration.
Comparator
Placebo mouth rinse, also administered three times per day over the same described period.
Primary question
How did the duration, in days, of severe oral mucositis (WHO Grades 3 or 4) compare between the AG013 and placebo groups during the stated treatment period?
Although the registry record names this as the primary efficacy outcome, it does not report group means, variability, or a between-group estimate for duration. Thus, the clinical question is clear from the registered endpoint, but the posted results do not establish the direction or precision of an efficacy comparison.
3. Trial Design
The registry record describes a phase 2, multicenter, randomized, double-blind, placebo-controlled study with a parallel-group model. Masking is recorded as quadruple. The planned enrollment was 200. The listed study population was people with head and neck cancers receiving concomitant chemoradiation therapy, and the condition of interest was oral mucositis.
Participants in both groups were to rinse three times per day. AG013 or placebo began at the start of radiotherapy and continued until 2 weeks after its completion; the active treatment phase was described as 7 to 9 weeks, depending on radiotherapy duration. The primary outcome timeframe is described similarly, from the start of radiation therapy until 2 weeks following completion.
In general, random allocation is intended to make treatment groups comparable on average, including for factors that are not measured. A parallel-group design assigns each participant to a treatment group for comparison rather than describing a crossover between treatments. Masking is intended to reduce the influence of treatment knowledge on care, outcome assessment, and reporting. The registry record labels masking as quadruple but does not identify which roles were masked.
The study start is listed as 2017-07-18, and primary completion is listed as 2020-03-31. The current status is terminated. The reason for termination, the timing of the termination decision, and any consequences for enrollment or follow-up are not reported in the registry record. The record also does not report the original protocol's sample-size justification or detailed operational procedures. The listed enrollment is a design characteristic; it should not be interpreted as the number analyzed for the primary outcome.
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: 3 patients were randomized but never received study drug and are excluded from the safety analysis set.
Overall Study
| Stage | AG013 | Placebo |
|---|---|---|
| STARTED | 100 | 100 |
| COMPLETED | 67 | 60 |
| NOT COMPLETED | 33 | 40 |
Reasons for not completing this period:
| Reason | AG013 | Placebo |
|---|---|---|
| Adverse Event | 4 | 2 |
| Death | 0 | 1 |
| Lost to Follow-up | 1 | 1 |
| Withdrawal by Subject | 12 | 27 |
| Symptomatic deterioration | 0 | 1 |
| Non-compliance | 2 | 0 |
| Other | 14 | 8 |
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 | AG013 | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 100 | 100 | 200 | |
| Age, Continuous | years | 60.4 (SD 9.98) | 60.4 (SD 9.10) | 60.4 (SD 9.53) |
| Sex: Female, Male: Female | Participants | 19 | 16 | 35 |
| Sex: Female, Male: Male | Participants | 81 | 84 | 165 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 7 | 9 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 91 | 81 | 172 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 7 | 12 | 19 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Black or African American | Participants | 4 | 3 | 7 |
| Race (NIH/OMB): White | Participants | 93 | 92 | 185 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 | 4 | 6 |
| Region of Enrollment: United States | participants | 65 | 65 | 130 |
| Region of Enrollment: Europe | participants | 35 | 35 | 70 |
6. Primary Endpoint
The registry lists the primary outcome as Efficacy of AG013 Compared to Placebo for Reducing OM as Measured by Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4), measured over From the start of radiation therapy (RT) until 2 weeks following its completion, 7 to 9 weeks depending on the duration of CRT..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Days |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the duration, measured in days, of severe oral mucositis, defined as WHO Grades 3 or 4. The endpoint is framed as a mean, with standard deviation as the stated measure of dispersion. Its timeframe starts at the beginning of radiation therapy and extends until 2 weeks after completion, with the overall active treatment period described as 7 to 9 weeks depending on the duration of chemoradiation therapy.
Duration is a continuous measure: it represents time spent with the specified severity rather than simply whether severe mucositis occurred. In general, measuring duration can describe how long a severe condition persists among the participants included in the relevant analysis. A group mean summarizes the average duration, while a standard deviation describes how spread out individual durations are around that average. Neither quantity alone describes the full distribution, and interpretation depends on how participants without the event or with incomplete observation are handled.
The registry record does not report the group means, standard deviations, participant counts contributing to this endpoint, or a treatment contrast. It also does not report the endpoint's detailed operational rules, such as how onset and resolution were determined or how duration was treated for participants who did not reach severe grades. Those details are important for understanding exactly what the mean represents, but they are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a primary efficacy question but does not post the data needed to answer it. There are no reported group means or standard deviations for duration of severe oral mucositis, and no reported between-group estimate, confidence interval, or p-value. The direction, size, and precision of any efficacy difference therefore cannot be characterized from the posted results.
The record lists one outcome measure and zero analyses. It also indicates that the primary outcome has several categories or time points and was not reduced to one comparison. This means that no single contrast should be inferred from the endpoint title or the study objective. The registry record does not explain which categories or time points were considered, or how they would have contributed to a primary analysis.
The status is terminated, but that status alone does not explain why the study ended or indicate what happened to the planned analysis. The record lists planned enrollment of 200, while safety counts are reported for 100 participants at risk in the AG013 group and 97 in the placebo group. These safety denominators do not establish the number enrolled, randomized, followed, or analyzed for the primary efficacy outcome. Reasons for differences between the listed enrollment and the safety denominators are not reported in the registry record.
In general, a confidence interval expresses the uncertainty around an estimated contrast, while a p-value addresses how compatible the observed data are with a specified statistical model and null hypothesis. Neither can be interpreted in this case because no primary efficacy estimate or inferential result is reported. A missing result is not evidence that the groups were the same, and it is not evidence of a difference.
The posted safety counts describe events in the groups at risk, but they do not substitute for the missing efficacy analysis. Nor do the posted counts by themselves establish that an event was caused by AG013 or placebo. The registry record does not provide a narrative explanation of the termination, an efficacy analysis, or enough information to judge how complete outcome follow-up was.
9. Statistical Methods Explained
The statistical information in the registry record is sufficient to identify the planned comparison and the broad form of the primary endpoint, but not to reconstruct an efficacy analysis. The endpoint is a continuous duration in days, summarized as a mean with standard deviation. The trial is described as randomized and parallel-group, with AG013 compared with placebo. No fitted statistical model, adjusted analysis, or numerical treatment contrast is reported in the registry record.
What does a mean difference represent?
In general, a mean difference compares average values between groups. For this endpoint, a contrast would concern average days of severe oral mucositis as defined by the registry. A contrast needs a clear sign convention, analysis population, and method for calculating duration. The registry record does not report a mean difference or specify a sign convention. Without the group summaries and the treatment contrast, there is no basis for describing the direction or magnitude of the primary result.
A standard deviation describes variation among observations within a group; it is not the same as uncertainty in a group mean or uncertainty in a difference between groups. In general, an interval estimate for a treatment contrast incorporates both the amount of information and variability in the data. Because the relevant estimates and intervals are not reported in the registry record, the precision of the primary comparison cannot be assessed.
How does randomization relate to the comparison?
In general, random assignment is used to reduce systematic differences between groups at the start of a trial. It can support a causal interpretation when the assigned groups are analyzed appropriately and follow-up, outcome measurement, and missing data are handled adequately. Randomization does not guarantee that all group characteristics will be identical, and it does not by itself address missing outcomes or deviations from treatment. The registry record states that allocation was randomized but does not report the sequence-generation or allocation-concealment procedures.
The parallel-group model means that the comparison is between groups assigned to AG013 or placebo. The record describes quadruple masking. In general, masking can reduce bias arising when treatment knowledge influences participant reports, clinical decisions, or outcome assessments. The record does not specify which people were masked, whether masking was maintained, or whether it was assessed.
What can be inferred from the planning illustration?
The sample-size assumptions describe a planning illustration based on an observed effect, not the trial's own design justification. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such a calculation is a planning exercise, not observed power and not a result of the randomized comparison. It depends on the effect used as its starting point and on the assumptions stated for the illustration. The registry record does not report the original sample-size justification.
For this continuous outcome, the sample-size description refers to participants per arm for a power target. It does not provide a basis for claiming that the completed study had a particular probability of detecting an effect. In general, observed power calculated from an observed effect does not replace interpretation of the effect estimate and its uncertainty. Since the primary outcome's observed effect is not reported in the registry record, no numerical planning interpretation can be drawn from that description.
Why does the outcome structure matter?
The registry record indicates that the primary outcome has several categories or time points and was not reduced to one comparison. This matters because results across categories or times may answer different questions. In general, a statistical analysis needs to define which contrast is primary and how other comparisons will be interpreted. If many comparisons are made, the chance of finding an apparently unusual result by chance can increase unless the analysis plan accounts for multiplicity. The registry record does not report an analysis plan or a multiplicity procedure.
In general, the distribution of duration data and the handling of participants who never develop severe mucositis can affect the choice and interpretation of an analysis. An average may not fully represent a skewed distribution, and incomplete observation can affect the observed duration. These are general considerations, not claims about the distribution in this trial. The registry record does not report a distributional assessment, a model for the endpoint, or rules for participants without severe mucositis.
Overall, the registry description supports a statistical reading of the planned endpoint and design, but not a numerical efficacy conclusion. The primary analysis method, analysis population, missing-data approach, and inferential results are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies the primary outcome as duration of severe oral mucositis but also indicates that it has several categories or time points and was not reduced to one comparison. It does not report a hierarchy of comparisons, a prespecified primary contrast among those categories or times, or an adjustment for multiple testing. The number and relationships of the intended comparisons are not reported in the registry record.
In general, multiplicity arises when researchers assess multiple outcomes, time points, or subgroup comparisons. If each is tested separately, the chance of at least one apparently positive result can increase. Prespecifying a primary comparison or adjusting the interpretation of multiple tests can help address this issue. These are general statistical principles; the registry record does not specify whether any such strategy was used.
Missing-data procedures are not reported in the registry record. The record does not say how participants who discontinued treatment, had incomplete follow-up, or did not develop severe oral mucositis were handled for the duration endpoint. It does not describe imputation, censoring, sensitivity analyses, or other approaches. In general, missingness can affect both the estimate and its uncertainty, particularly when the likelihood of missing data is related to outcomes or treatment experience.
Analysis populations are also not reported in the registry record. It is not stated whether the primary analysis was intended to include all randomized participants, participants who received treatment, or another defined group. The listed enrollment and safety denominators should not be assumed to identify the primary efficacy population. Because no primary efficacy analysis is posted, it is not possible to assess how these issues were handled.
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 |
|---|---|---|---|
| AG013 | 43 | 100 | 43.0% |
| Placebo | 25 | 97 | 25.8% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| AG013 | 2 of 100 |
| Placebo | 4 of 97 |
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 |
|---|---|
| AG013 | 98 of 100 |
| Placebo | 95 of 97 |
Most frequent serious adverse event terms
| Event term | Organ system | AG013 | Placebo |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 7 of 100 | 5 of 97 |
| Vomiting | Gastrointestinal disorders | 6 of 100 | 4 of 97 |
| Dysphagia | Gastrointestinal disorders | 6 of 100 | 3 of 97 |
| Pyrexia | General disorders | 3 of 100 | 4 of 97 |
| Acute kidney injury | Renal and urinary disorders | 5 of 100 | 2 of 97 |
| Pneumonia | Infections and infestations | 3 of 100 | 1 of 97 |
| Dehydration | Metabolism and nutrition disorders | 1 of 100 | 3 of 97 |
| General physical health deterioriation | General disorders | 2 of 100 | 1 of 97 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 2 of 100 | 1 of 97 |
| Febrile neutropenia | Blood and lymphatic system disorders | 1 of 100 | 2 of 97 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AG013 | Placebo |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 67 of 100 | 69 of 97 |
| Fatigue | General disorders | 56 of 100 | 58 of 97 |
| Constipation | Gastrointestinal disorders | 54 of 100 | 41 of 97 |
| Dysgeusia | Nervous system disorders | 43 of 100 | 49 of 97 |
| Dry mouth | Gastrointestinal disorders | 39 of 100 | 42 of 97 |
| Radiation skin injury | Injury, poisoning and procedural complications | 32 of 100 | 45 of 97 |
| Vomiting | Gastrointestinal disorders | 38 of 100 | 38 of 97 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 36 of 100 | 40 of 97 |
| Dysphagia | Gastrointestinal disorders | 33 of 100 | 39 of 97 |
| Diarrhoea | Gastrointestinal disorders | 27 of 100 | 43 of 97 |
Serious events with the highest arm-level rate: nausea (7.0%), vomiting (6.0%), dysphagia (6.0%), acute kidney injury (5.0%), pyrexia (4.1%).
The registry record lists serious adverse events for 100 participants at risk in the AG013 group and 97 in the placebo group. Serious adverse events were reported for 43 participants in the AG013 group and 25 in the placebo group. The record separately lists other adverse events for 98 participants in the AG013 group and 95 in the placebo group. Deaths are listed for 2 participants in the AG013 group and 4 in the placebo group.
These are descriptive counts, not estimates of treatment effect. The registry record does not provide an analysis comparing groups, an interval estimate, or a causal assessment. The deaths should not be attributed to treatment on the basis of these counts alone; causes and relatedness are not reported in the registry record.
The listed serious adverse-event terms include Nausea at 7.0%, Vomiting at 6.0%, Dysphagia at 6.0%, Acute kidney injury at 5.0%, Pyrexia at 4.1%, and Dehydration at 3.1%. The registry record does not specify an arm for these percentages or provide further detail about their calculation in the listed terms. These percentages should therefore be read as the registry's reported figures, not as a comparison between treatment groups.
In general, adverse-event counts depend on how events are defined, collected, and attributed, as well as on the number of participants observed and duration of observation. The registry record does not provide enough detail to interpret the safety counts as a comparative risk analysis.
12. What the Result Does, and Does Not, Mean
The registered question is whether AG013 mouth rinse changed the duration of severe oral mucositis compared with placebo during chemoradiation for head and neck cancer. The registry record describes a randomized, masked, parallel-group phase 2 study and specifies a continuous primary endpoint in days. It also posts selected safety counts. These details clarify what the trial set out to evaluate and what safety information is recorded.
The record does not report a primary efficacy estimate or analysis. It therefore does not show whether average duration differed between groups, how large any difference was, or how precisely it was estimated. The absence of a posted efficacy result cannot be interpreted as evidence of no difference, nor can the study objective be treated as evidence that an effect occurred.
The safety counts likewise do not establish that AG013 caused or prevented any event. They are counts in the groups listed as at risk, without a reported comparative analysis, uncertainty interval, or attribution details. The serious adverse-event term percentages are not identified by treatment group in the record.
In general, trial results are most informative when they include a clearly defined analysis population, a treatment-effect estimate, a measure of uncertainty, and details of missing-data handling. Those elements are not reported for the primary outcome in this registry record. The termination status is relevant context, but the reason for termination and its implications for data collection or analysis are not reported.
Accordingly, the posted information supports description of the design, endpoint, and selected safety counts, but not a conclusion about comparative efficacy. It also does not provide enough context for a complete assessment of comparative safety. Any interpretation should remain limited to what the registry record explicitly reports.
13. Why This Trial Matters Statistically
This trial illustrates why a registered clinical question and a reported statistical result are not the same thing. The record clearly describes a randomized comparison of AG013 mouth rinse and placebo, a defined population receiving chemoradiation, and a primary outcome focused on duration of severe oral mucositis. Those elements allow readers to identify the intended estimand at a broad level: a comparison of duration between groups during a specified treatment period.
At the same time, a design description cannot replace an outcome estimate. Without group summaries, a treatment contrast, and uncertainty measures, readers cannot assess the size or precision of the primary efficacy result. This distinction is important for statistical literacy: the absence of a reported result is not a null result, and an objective written in a registry is not evidence that the objective was achieved.
The endpoint also raises general issues common to duration outcomes. Interpretation depends on defining the start and end of an episode, deciding how people who never reach the severe threshold are represented, and addressing incomplete follow-up. Those choices can affect both the meaning of an average duration and the population to which it applies. The registry record does not report these details.
The posted safety information provides event counts and selected terms, but not comparative inference or attribution. Reading those figures as causal evidence would go beyond what the record states. The terminated status is another reason to distinguish the design as registered from the evidence actually reported: the reason and analytic consequences are not reported.
Statistically, the record is therefore useful for identifying the question and the information gaps. It cannot support a quantitative efficacy conclusion or a complete comparison of harms.
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 main trial-specific limitation is that the registry record does not report the primary efficacy results. Group means, standard deviations, a treatment contrast, confidence intervals, and p-values are not reported, so the primary question cannot be answered from the posted results. The record notes several categories or time points for the primary outcome without reducing them to one comparison, but does not explain their structure or intended analysis.
The primary endpoint is described as duration in days, but the operational definition is limited. The registry record does not report how onset and resolution were assessed, how repeated or interrupted episodes were handled, or how participants who did not reach WHO Grades 3 or 4 were incorporated. It also does not report an analysis population or methods for incomplete outcome data.
The status is terminated, and the reason for termination is not reported in the registry record. The record does not explain whether termination affected enrollment, follow-up, data quality, or the planned analysis. Planned enrollment is listed as 200, while the safety groups have different numbers at risk; the relationship between these counts and the primary efficacy population is not reported.
Safety interpretation is limited to posted counts and selected serious adverse-event terms. Comparative estimates, uncertainty, event relatedness, and further details about how the percentages were calculated are not reported. These limitations preclude interpreting the listed counts as evidence of a causal difference between groups.
Finally, the registry record does not report the original sample-size justification, detailed statistical analysis plan, multiplicity strategy, or missing-data procedures. These omissions limit assessment of whether the planned analyses matched the registered question and how robust any potential result would be.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy, Safety and Tolerability of AG013 in Oral Mucositis Compared to Placebo When Administered Three Times Per Day — NCT03234465.
- Registry record last updated 2020-11-23; status last verified 2020-10.
- Results first posted 2020-11-23.
- 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
NCT03234465 is a phase 2, randomized, multicenter, double-blind, placebo-controlled, parallel-group study of topical AG013 for oral mucositis in people with head and neck cancer receiving concomitant chemoradiation. The record lists quadruple masking and planned enrollment of 200. Participants were assigned to AG013 or placebo mouth rinse three times per day during radiotherapy and until 2 weeks after completion; the active treatment phase was described as 7 to 9 weeks.
The primary endpoint was duration in days of severe oral mucositis (WHO Grades 3 or 4). The study start is listed as 2017-07-18, primary completion as 2020-03-31, and status as terminated. The record posts selected safety counts but does not report a primary efficacy analysis, the reason for termination, or the detailed statistical plan.