Safety and Efficacy of ALD518 for Reducing Oral Mucositis in Head and Neck Cancer Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of ALD518 for Reducing Oral Mucositis in Head and Neck Cancer Subjects (NCT01403064), a randomized phase 2 study. The primary outcome is Percent of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities.

2. Clinical Question

The trial addressed oral mucositis in the context of head and neck cancer treatment. The registry’s brief summary says the study was intended to evaluate the safety and efficacy of ALD518 in modifying the course of oral mucositis during concomitant chemotherapy and radiotherapy. Its listed secondary outcomes include ulcerative and severe oral mucositis at varying cumulative radiation doses, duration and time to onset of mucositis, ALD518 plasma concentration, and an Oral Mucositis Daily Questionnaire score.

The primary outcome is broader than a single clinical event: it combines the percentage of participants with adverse events, serious adverse events, and clinically significant laboratory abnormalities. The posted results include group counts for serious and other adverse events, but do not provide a single comparative estimate for the primary outcome. Numeric results for the listed oral-mucositis outcomes are not reported in the registry record.

3. Trial Design

The registry record identifies this as a phase 2, randomized, double-blind, placebo-controlled trial with a parallel-group design. It lists quadruple masking. These design features describe how treatment assignment and masking were organized; they do not, on their own, establish that the groups were comparable in every respect or that any observed difference was caused by treatment.

The record lists ALD518 and 0.9% saline as interventions. The arm descriptions identify Open Label ALD518, ALD518 Dose 1, ALD518 Dose 2, and Placebo, but do not give dose details in those descriptions. The posted safety results use the group labels Placebo, ALD518 (160 mg), and ALD518 (320 mg). For the safety analysis, the two treatment groups that received 160 mg—open label and randomized—were combined, as prespecified in the record. Participants were analyzed according to the treatments they received.

The registry lists an enrollment of 76. The primary outcome timeframe is up to 15 months. The recorded start is 2011-07, the primary completion is 2013-04, and the status is terminated. The reason for termination is not reported in the registry record. No further details about recruitment, treatment administration, visit schedules, or follow-up procedures are reported in the registry record.

The analysis is described as using a safety population defined as any subject who received at least 1 dose of ALD518 or placebo. This population definition is relevant when reading the adverse-event counts: the results are not described as an analysis of everyone enrolled regardless of treatment receipt. The registry record does not report a separate efficacy-analysis population or enough detail to determine how participants with incomplete follow-up were handled.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population (SP) defined as any subject who received at least 1 dose of ALD518 or placebo. Subjects were analyzed based on the treatments they received. As pre-specified, the two treatment groups that received 160 mg (open label and randomized) were combined into one 160 mg group for analysis purposes of this endpoint.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percent of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities, measured over Up to 15 months.

The primary outcome is the percentage of participants with adverse events, serious adverse events, and clinically significant laboratory abnormalities, assessed up to 15 months. It is a safety endpoint: it describes the occurrence of events or laboratory findings during the trial rather than the effect of ALD518 on oral mucositis. The posted record gives group counts for serious and other adverse events, but does not provide a single primary-outcome percentage or a comparative estimate covering all the endpoint’s components.

Safety endpoints are used to characterize unwanted events and laboratory abnormalities observed during exposure to a study intervention. Reporting the number of affected participants alongside the number at risk can help readers understand the scale of observed events within each group. A percentage can also make event frequencies easier to compare across groups of different sizes, but it does not by itself show whether a difference is statistically precise or attributable to treatment.

The registry record does not define which events count as clinically significant laboratory abnormalities, explain how event severity was classified, or give detailed rules for attributing events to treatment. It also does not report an inferential comparison for this primary outcome. The listed secondary outcomes concern oral mucositis, including ulcerative and severe mucositis, duration, onset, plasma concentration, and questionnaire scores. Their numeric results are not reported in the registry record. Consequently, the primary safety endpoint should not be read as a direct measure of efficacy against oral mucositis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For an outcome expressed as a percentage of participants with an event, the basic descriptive information is the count of participants who experienced the event and the number of participants at risk or assessed. The posted serious and other adverse-event results give these counts by group. This makes the reported quantities interpretable as observed event frequencies within the safety population. It does not supply a statistical comparison or account for uncertainty around those frequencies.

What does a confidence interval convey?

General: a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the method used to construct it. A narrow interval indicates greater precision than a wide interval, while an interval spanning values consistent with very different effects may leave substantial uncertainty. A confidence interval does not measure the probability that a particular treatment effect is true, and it cannot address biases or missing information in the underlying data. The registry record does not report confidence intervals for the primary safety outcome.

How should group comparisons be assessed?

General: comparing event frequencies requires an estimate of the difference or another prespecified contrast, together with an assessment of its uncertainty. Looking at counts alone does not provide that assessment. When counts are small, estimates can be imprecise; when outcome definitions or follow-up differ, simple comparisons may also be difficult to interpret. The record does not report a single primary-outcome contrast or the inferential method used for such a comparison. The sponsor’s own analysis cannot be assessed from the posted information because no corresponding analysis is reported.

Why does the outcome definition matter?

The primary outcome includes adverse events, serious adverse events, and clinically significant laboratory abnormalities. These are related safety domains, but they are not interchangeable. A participant may experience an event in more than one category, and the record does not explain how overlap was handled in a combined outcome. Nor does it specify the criteria for a clinically significant laboratory abnormality. Without those details and a clear analysis definition, readers should treat the component counts as separate descriptive information rather than assume they form a single composite result.

General: a composite endpoint combines multiple event types into one outcome. It can capture a broader range of experiences, but its interpretation depends on the components, their clinical importance, and the rule for combining them. If common, less severe events dominate a composite, the overall result may not reflect the pattern of rarer, more serious events. The record’s primary outcome names multiple categories, but does not report a single combined result or details sufficient to assess the contribution of each component.

What can be inferred from the posted safety counts?

The counts show how many participants in each listed group were reported to have serious or other adverse events. They do not show the duration of events, recurrence, severity beyond the serious-event classification, timing relative to treatment, or treatment attribution. Those details are not reported in the registry record. In general, event counts are descriptive; a causal interpretation requires appropriate design, analysis, and complete reporting, and even a randomized trial’s result must be interpreted in light of uncertainty and data quality.

The registry says participants were analyzed based on the treatments they received. General: this is a description of the analysis population and does not necessarily mean that every participant was analyzed according to original random assignment. The record does not provide enough information to determine whether the posted group labels align with initial assignment for every participant, how treatment changes were handled, or how deviations from the planned treatment were addressed.

How do planning calculations differ from trial results?

General: sample-size planning calculations illustrate how many participants per arm might be needed under chosen assumptions about the effect to detect, significance level, allocation, and statistical method. Such calculations are planning illustrations, not observed power and not evidence that the trial achieved a particular level of power. The record describes illustrations based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says time-to-event illustrations use the total number of events, while other illustrations use participants per arm. The numerical illustration results are not reported in the registry record, and these assumptions should not be mistaken for the trial’s own design justification or analysis plan.

General: over-dispersion means that outcome variability is greater than a model assumes. When present, it can make standard errors too small and confidence intervals too narrow if the analysis does not account for it. The posted information does not describe a model for the binary safety outcomes or report whether over-dispersion was assessed. No conclusion about the use or adequacy of such a model can be drawn from the record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome names several categories: adverse events, serious adverse events, and clinically significant laboratory abnormalities. The registry also lists secondary outcomes at varying cumulative radiation doses and across different measures of oral mucositis, along with duration, onset, plasma concentration, and questionnaire scores. Assessing multiple outcomes or time points can increase the chance of finding an apparently notable result by chance when many statistical tests are performed. General: methods for handling multiplicity can include prespecifying a limited set of comparisons, adjusting significance thresholds, or interpreting results as exploratory. The registry record does not report a multiplicity strategy.

The record does not report a single primary-outcome comparison and lists 0 analyses. Numeric results for the listed secondary outcomes are not reported in the registry record. As a result, there is no reported set of outcome estimates or tests from which to assess how multiplicity was addressed or how any secondary findings should be interpreted.

The safety population includes people who received at least 1 dose of ALD518 or placebo, and participants were analyzed based on the treatments they received. The registry record does not report how missing outcome measurements were handled, whether participants with incomplete follow-up were excluded from particular outcomes, or whether any imputation was used. It also does not report the amount or pattern of missing data. General: missingness can affect estimates if the chance of an outcome being unobserved is related to the participant’s health, treatment, or event history. Without missing-data details, the completeness and potential selection effects of the analyses cannot be evaluated.

The record says the two 160 mg treatment groups were combined for analysis as prespecified. It does not report the rationale for that choice or provide a separate analysis of those groups. Further details about randomization procedures, allocation concealment, subgroup analyses, interim analyses, and the statistical analysis plan are not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nausea (9.4%), general physical health deterioration (9.4%), pyrexia (8.7%), dehydration (8.7%), oral pain (6.2%).

The serious adverse-event figures are counts of affected participants and participants at risk in each posted group: Placebo, 7 of 23; ALD518 (160 mg), 15 of 32; and ALD518 (320 mg), 8 of 21. The other adverse-event counts are Placebo, 22 of 23; ALD518 (160 mg), 32 of 32; and ALD518 (320 mg), 21 of 21. These quantities describe events reported in the safety population, which the record defines as any subject who received at least 1 dose of ALD518 or placebo.

Serious adverse events are a subset or classification of events that should not be treated as equivalent to all other adverse events. The registry record does not provide the criteria used to classify seriousness, the timing or duration of each event, or whether events were judged related to treatment. It lists deaths as 0 for Placebo, 4 for ALD518 (160 mg), and 2 for ALD518 (320 mg), but does not report cause, timing, or attribution. The count alone cannot establish a relationship to treatment.

These are descriptive group figures, not a comparative test. The registry record does not report an uncertainty interval or inferential comparison for these counts. Differences in the counts should not be read as evidence of a treatment effect without those analyses and fuller clinical context.

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

The registry record documents a phase 2 randomized, placebo-controlled study of ALD518 in people with head and neck cancer receiving concomitant chemotherapy and radiotherapy. It reports adverse-event counts for the safety population and identifies a primary outcome focused on adverse events, serious adverse events, and clinically significant laboratory abnormalities. These figures are useful for describing what was recorded in the study groups, but do not by themselves establish a comparative safety effect.

The record also lists oral-mucositis outcomes, including ulcerative and severe mucositis, duration and time to onset, plasma concentration, and questionnaire scores. Numeric results for those outcomes are not reported in the registry record. Consequently, the posted information does not establish whether ALD518 changed the course of oral mucositis. It also does not provide a single reported primary-outcome estimate, confidence interval, or statistical test that would quantify comparative uncertainty.

The posted counts do not establish causation. A randomized design can support causal comparisons when treatment assignment, follow-up, outcome definitions, and analysis are adequately implemented and reported, but the record does not provide enough detail to evaluate all of those elements. In particular, it does not report treatment attribution for adverse events or deaths, missing-data handling, or a detailed statistical analysis plan.

The trial is listed as terminated. The reason for termination is not reported in the registry record, so termination cannot be interpreted as evidence of benefit, harm, futility, or an operational decision. The results should be understood as the descriptive safety information and limited outcome reporting recorded in the registry, rather than as a complete account of the trial’s clinical or statistical findings.

13. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between a trial’s clinical objective and its registered primary outcome. The brief summary frames the study around modifying oral mucositis during cancer treatment, while the primary outcome is a safety measure covering adverse events, serious adverse events, and clinically significant laboratory abnormalities. The listed secondary outcomes address mucositis more directly, but their numeric results are not reported in the registry record.

The record also shows why event counts need context. Counts of participants with serious or other adverse events describe what was recorded within the safety population. They are not, on their own, estimates of a treatment difference with quantified uncertainty. Without a reported contrast, confidence interval, or test, the counts cannot answer whether group differences are statistically precise or attributable to the intervention.

The trial’s reporting further highlights the importance of endpoint definitions and analysis populations. The two 160 mg treatment groups were combined as prespecified, and the safety population includes people who received at least 1 dose. These details shape how the posted results should be read. Information about missing data, event attribution, and the handling of the several primary-outcome categories is not reported in the registry record, limiting assessment of the analysis.

Finally, a terminated status is not an explanation of what happened or why. Without a reported reason, it cannot stand in for an outcome or a statistical conclusion. Careful interpretation separates the design information, descriptive safety data, and unreported efficacy results, rather than treating them as interchangeable evidence.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary outcome combines several safety categories, but the registry record does not report a single combined estimate or explain how overlap between categories was handled. It also does not define clinically significant laboratory abnormalities or give detailed event-classification rules. These omissions limit interpretation of the endpoint’s scope and of any group comparison.

The posted adverse-event counts are descriptive. No confidence intervals or inferential tests for a primary comparison are reported, and the record lists 0 analyses. The record does not report event timing, duration, severity beyond serious-event classification, or treatment attribution. For deaths, cause, timing, and relationship to treatment are not reported in the registry record.

The safety population is defined by treatment receipt, and the record says participants were analyzed based on treatments received. The record does not provide missing-data amounts or methods, explain how incomplete follow-up was handled, or report whether analyses followed initial random assignment. These gaps limit evaluation of possible selection effects and the comparability of the groups in the analyses.

Numeric results for the secondary oral-mucositis outcomes are not reported in the registry record. The record also does not report the reason the trial was terminated, the statistical analysis plan, multiplicity handling, interim analyses, or sample-size justification. These missing details prevent a fuller assessment of the trial’s efficacy findings, analysis choices, and the implications of termination.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy of ALD518 for Reducing Oral Mucositis in Head and Neck Cancer Subjects — NCT01403064.
• Registry record last updated 2021-05-11; status last verified 2021-04.
• Results first posted 2021-05-11.
• 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.

18. Record Summary

NCT01403064 is a phase 2 randomized, double-blind, placebo-controlled, parallel-group trial of ALD518 in people with head and neck cancer receiving concomitant chemotherapy and radiotherapy. The registry lists quadruple masking, enrollment of 76, and a status of terminated. The reason for termination is not reported in the registry record.

The primary outcome is the percentage of participants with adverse events, serious adverse events, and clinically significant laboratory abnormalities, assessed up to 15 months. The posted safety results report serious and other adverse-event counts for Placebo, ALD518 (160 mg), and ALD518 (320 mg), with the two 160 mg treatment groups combined as prespecified.

The record lists oral-mucositis secondary outcomes, but their numeric results are not reported in the registry record. No single comparative primary-outcome estimate, confidence interval, or inferential test is reported. The available figures therefore describe observed safety events without establishing a comparative treatment effect.