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 Phase 2a Study to Evaluate Suppression of Methotrexate-induced Mucositis by TK112690 (NCT04046250), a randomized phase 2 study. The primary outcome is Mucositis.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04046250 |
| Phase | Phase 2 |
| Condition | Mucositis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 22 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Tosk, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with SCCHN who had failed at least one prior treatment of chemotherapy and/or radiation. The brief summary describes patients receiving weekly methotrexate, and the official title refers to patients with recurrent or residual SCCHN.
Intervention
TK112690 was administered alongside methotrexate. The brief summary describes TK112690 at 45 mg/kg, with an infusion one hour before methotrexate and a second treatment five hours afterward. Methotrexate was administered as an intravenous infusion at 45 mg/m2 weekly for 4 consecutive weeks.
Comparator
Placebo was administered alongside the same methotrexate schedule. The registry describes a nutritional supplement given two hours before methotrexate in both treatment descriptions.
Primary question
The trial asked whether mucositis scores differed between the TK112690 and placebo groups at 4 weeks. Scores were to be assessed using the NCI/CTCAE and WHO scales, for which higher scores indicate greater mucositis. The registry record does not report the group scores or the comparison results.
3. Trial Design
This was a randomized, placebo-controlled, parallel-group phase 2a study. The official title describes the study as multi-center and partially blinded, while the registry’s masking field says triple masking. The record does not further describe who was masked or how masking was maintained. It reports an enrollment of 22 and a completed status.
The study began on 2019-05-15, and its primary completion date was 2019-10-10. Participants were assigned to TK112690 or placebo while receiving methotrexate. The brief summary specifies methotrexate at 45 mg/m2 by intravenous infusion weekly for 4 consecutive weeks. It also describes a nutritional supplement two hours before methotrexate, a first TK112690 or placebo infusion one hour before methotrexate, and a second treatment five hours after methotrexate. The stated TK112690 dose was 45 mg/kg.
The population was described as patients with SCCHN who had failed at least one prior treatment of chemotherapy and/or radiation. The official title refers to recurrent or residual SCCHN. The registry record does not give further eligibility details, the randomization procedure, the allocation ratio, or the number of participants assigned to each arm for the primary outcome. The safety record lists 11 participants at risk in each arm; those safety counts do not establish the analysis population for the primary endpoint.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | TK112690 | Placebo |
|---|---|---|
| STARTED | 11 | 11 |
| COMPLETED | 8 | 7 |
| NOT COMPLETED | 3 | 4 |
Reasons for not completing this period:
| Reason | TK112690 | Placebo |
|---|---|---|
| Death | 0 | 1 |
| Withdrawal by Subject | 3 | 3 |
Analysis population for the primary outcome, as defined in the registry: Patients with SCCHN who have failed at least one prior treatment of chemotherapy and/or radiation
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 | TK112690 | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 11 | 11 | 22 | |
| Age, Continuous | years | 54 (SD 11) | 49 (SD 13) | 52 (SD 12) |
| Sex: Female, Male: Female | Participants | 7 | 8 | 15 |
| Sex: Female, Male: Male | Participants | 4 | 3 | 7 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 11 | 11 | 22 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: India | participants | 11 | 11 | 22 |
6. Primary Endpoint
The registry lists the primary outcome as Mucositis, measured over up to 4 Weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary outcome is mucositis measured as a score on a scale, with the registry specifying a mean and standard deviation for each group. Assessment was described at 4 weeks using two grading systems: NCI/CTCAE and WHO. Both are ordinal grading scales, and a higher score on either scale indicates greater mucositis. The registry lists grades from 0 through 5 for NCI and from 0 through 4 for WHO, with descriptions ranging from no mucositis to severe or life-threatening effects. The NCI/CTCAE scale includes a grade for death.
Mucositis is the condition the study aimed to evaluate in the context of methotrexate treatment. A score gives a structured way to record severity, while group means provide a summary for comparing the assigned treatments. The registry states that scale-specific means were to be calculated and compared using Student's t-test. Because the outcome description names two scales at the same time point, the registry record does not reduce the primary outcome to one comparison. It does not report the group means, standard deviations, or test results, so the magnitude and precision of any group difference cannot be assessed from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes a randomized comparison of TK112690 and placebo, each administered alongside methotrexate. It identifies mucositis scores at 4 weeks on the NCI/CTCAE and WHO scales as the primary outcome. However, the registry record does not report the observed mucositis scores, group means, standard deviations, or a statistical comparison. It therefore does not support a quantitative conclusion about how the groups differed on either scale.
The stated outcome analysis would compare group means using Student's t-test. That identifies a planned analytic approach, not an observed result. The record lists no analysis records, and there is no reported p-value, confidence interval, or effect estimate for the mucositis outcome. Without an estimate and its uncertainty, readers cannot assess either the direction or the precision of a possible difference. The completed status and enrollment of 22 describe trial conduct, but do not substitute for the missing outcome results.
The adverse-event information is separate from the primary efficacy outcome. Among 11 participants at risk in each arm, the record lists serious adverse events affecting 0 participants in the TK112690 arm and 2 in the placebo arm. It also lists other adverse events affecting 1 participant in the TK112690 arm and 7 in the placebo arm, and deaths of 0 and 1, respectively. These counts describe the posted safety record; they do not provide the missing mucositis scores or establish a treatment effect on mucositis. The record does not supply enough detail to characterize the events beyond the categories and terms it lists.
Confidence intervals, when reported, describe the range of values reasonably compatible with an estimated effect under the model used. A narrow interval generally indicates greater precision, while a wide interval indicates less precision. No interval for the primary comparison is reported in the registry record, so the precision of any mucositis difference cannot be judged. Likewise, the absence of reported statistical tests means that statistical significance cannot be assessed from this record.
The registry’s description of the primary outcome names both scales as primary at 4 weeks. It does not explain whether both were intended to be confirmatory, how they were prioritized, or how multiplicity was handled. That uncertainty matters when interpreting any comparison, but there are no reported comparisons to interpret. Conclusions should therefore remain limited to the design, outcome definitions, and safety counts recorded, rather than inferring efficacy from the trial’s completion or its small enrollment.
9. Statistical Methods Explained
What does a mean score summarize?
The primary outcome is described as a continuous measure summarized by a mean and standard deviation, even though the underlying NCI/CTCAE and WHO grades are ordinal categories. A group mean provides a compact summary of scores, and the standard deviation describes how dispersed individual scores are around that mean. These summaries can make a group comparison straightforward, but they do not show the full distribution of scores or how many participants were in each grade. The registry record does not report the actual means, standard deviations, or grade distributions.
Both grading systems assign higher scores to more severe mucositis. The scales have different grade ranges and descriptions, so their numerical values should be interpreted within their own definitions rather than treated as interchangeable measurements. The record says scale-specific means were to be calculated and compared. It does not describe any conversion between scales, nor does it report whether the two scale results agreed.
What does the stated t-test do?
The registry states that group means would be compared using Student's t-test. In general, a two-sample t-test evaluates whether the observed difference between two group means is large relative to the variability and sample size. Its assumptions concern the sampling behavior of the mean and the way observations vary within groups. The method does not, by itself, account for multiple outcome scales, repeated observations, missing scores, or other sources of bias. The record does not describe any additional adjustment or modeling strategy.
The record does not post a t-test statistic, p-value, estimate of the mean difference, or confidence interval. Consequently, the stated method cannot be used to reconstruct a result from the registry entry. Recalculation would require the relevant group-level outcome summaries, which are not reported. The registry’s safety counts do not supply those summaries.
How should uncertainty be understood?
Statistical uncertainty concerns how much an estimated effect might vary across samples under the analysis assumptions. A confidence interval is one way to communicate that uncertainty around an estimate. It does not describe every possible source of error, and it does not guarantee that a result is clinically important. No interval or primary-outcome effect estimate is reported in the registry record, leaving both the direction and precision of the comparison unknown.
General statistical considerations include the distribution of scores, the amount of variation within each group, whether observations are independent, and the handling of incomplete measurements. With ordinal scores, the group mean may not convey whether a difference reflects a shift across many participants or a small number of more severe scores. The record gives scale definitions but no score-level data that would allow those patterns to be examined. It also does not report a diagnostic assessment of the assumptions behind the t-test.
What can the planning assumptions establish?
The registry includes assumptions for a planning illustration: two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such assumptions describe a hypothetical planning calculation, not the trial’s own design rationale or its observed findings. Any participant counts from a planning illustration would be prospective planning quantities, not observed power. The registry record does not report a sample-size justification, and it does not provide a primary-outcome effect estimate from which a reader could judge that illustration.
Sample-size calculations depend on the target effect, outcome variability, chosen error rate, allocation, and model assumptions. If any of these inputs differ from the eventual study, the resulting planning quantity may not describe the trial as conducted. Here, the record does not state that its assumptions were used to set enrollment. It also does not report a protocol rationale, interim-analysis plan, or statistical analysis plan. These details should not be inferred from the planning assumptions.
Finally, the registry reports a completed study and enrollment of 22, but those details alone do not establish the number included in the primary analysis, the completeness of outcome collection, or the adequacy of precision. The primary endpoint analysis population and missing-data handling are not reported in the registry record. Without those details and without outcome summaries, the statistical methods can be described, but the primary comparison cannot be evaluated.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome description names two assessments at 4 weeks: NCI/CTCAE and WHO mucositis grades. The registry record does not say whether these were treated as co-primary outcomes, whether one was intended to take precedence, or whether a multiplicity adjustment was planned. When multiple outcomes or comparisons are assessed, the chance of a false positive across the set can differ from the chance associated with a single test. General methods for addressing multiplicity include defining a hierarchy or adjusting the testing procedure, but no approach is reported for this study. Since the primary scores and tests are not posted, the practical effect of any multiplicity approach cannot be examined.
The record also does not describe missing-data rules, imputation, or sensitivity analyses. It does not report how many participants had usable scores at 4 weeks on either scale, or whether all randomized participants were included in the primary analysis. The analysis populations, including any intention-to-treat or per-protocol population, are not reported in the registry record. Enrollment and safety counts do not establish endpoint completeness or analysis membership.
The registry’s stated t-test describes a comparison of means, but does not resolve these reporting gaps. Without an analysis population, missing-data accounting, and a stated approach to the two named scales, readers cannot determine how the outcome analysis was implemented or how robust it may be to incomplete data and multiple testing.
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 |
|---|---|---|---|
| TK112690 | 0 | 11 | 0.0% |
| Placebo | 2 | 11 | 18.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| TK112690 | 0 of 11 |
| Placebo | 1 of 11 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| TK112690 | 1 of 11 |
| Placebo | 7 of 11 |
Most frequent serious adverse event terms
| Event term | Organ system | TK112690 | Placebo |
|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 0 of 11 | 2 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | TK112690 | Placebo |
|---|---|---|---|
| GI Disorders | Gastrointestinal disorders | 1 of 11 | 7 of 11 |
Serious events with the highest arm-level rate: neutropenia (18.2%).
The safety record lists 11 participants at risk in each arm. Serious adverse events affected 0 participants in the TK112690 group and 2 in the placebo group. Other adverse events affected 1 participant in the TK112690 group and 7 in the placebo group. The record lists 0 deaths in the TK112690 group and 1 in the placebo group. These are counts, not estimates adjusted for exposure or follow-up duration.
Neutropenia is listed as the top serious adverse-event term, at 18.2%. The registry record does not give further details about the event, including its timing, severity distribution, or relationship to treatment. The listed group counts should be read as descriptive safety information for this study, not as a complete comparison of risk. The record does not provide event-level detail, exposure-adjusted rates, or uncertainty estimates. These safety entries also do not replace the unreported primary mucositis outcome.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized phase 2a study compared TK112690 with placebo alongside methotrexate in patients with SCCHN who had failed at least one prior treatment of chemotherapy and/or radiation. It also provides the intended mucositis scales, their scoring direction, and a stated comparison of group means using Student's t-test. Those details explain the question the study was designed to address.
The record does not establish what the primary outcome showed. No mucositis group means, standard deviations, effect estimates, confidence intervals, or p-values are reported. It is therefore not possible to state whether the scores were higher or lower in either group, whether a difference was statistically distinguishable from chance under the stated method, or how precisely any difference was estimated. No conclusion about treatment effect on mucositis follows from the completion status or enrollment alone.
The safety entries describe counts of participants affected by event categories and deaths. They do not establish comparative causation or provide a complete risk assessment. The registry record does not report enough context to determine how events were assessed or how the groups’ time at risk compares.
More generally, a statistical comparison is not the same as a clinical judgment. Even when an estimate and uncertainty are available, interpretation depends on the outcome’s meaning, study conduct, and the relevance of the population and treatment schedule. In this case, the primary estimate and its uncertainty are missing, so that broader interpretation cannot be made from the posted results. The findings should be described as unavailable in the registry record, rather than treated as evidence for either benefit or lack of benefit.
13. Why This Trial Matters Statistically
This trial illustrates the difference between a study’s design record and a report of its findings. The registry identifies a randomized, placebo-controlled comparison, a target population, treatment timing, and two defined mucositis scales. It also states how the scale-specific means were intended to be compared. These design details help readers understand the planned question, but they do not answer it without observed outcomes.
It is especially important that a completed status and enrollment count not be mistaken for evidence about the primary endpoint. Statistical interpretation requires an estimate and information about its uncertainty. Neither is reported for the mucositis comparison. The lack of analysis records in the registry further limits what can be learned about the implementation of the stated method.
The record also highlights why outcome definitions and multiplicity matter. Two scales are named as primary at the same assessment time, but the registry does not explain their relationship in the analysis or any strategy for interpreting multiple comparisons. These are relevant questions even when results are unavailable, because a complete account of analysis plans supports transparent interpretation.
Finally, the safety counts demonstrate that registry information can be informative while remaining incomplete. Counts of affected participants and deaths can be reported, but without event-level detail and uncertainty they cannot establish a full comparative safety profile. A careful statistical reading distinguishes what the record documents from what it leaves unresolved.
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 limitation for interpreting this trial is that the registry record does not report the primary mucositis outcome results. Group means, standard deviations, score distributions, effect estimates, and statistical tests are absent. This prevents assessment of both the direction and precision of the comparison on the NCI/CTCAE and WHO scales.
The outcome description includes two scales, but the record does not specify their relative status or how multiplicity was addressed. It does not report the primary analysis population, the number with observed scores, or how missing data were handled. The record also does not provide an analysis plan, a sample-size justification, or an explanation of the assumptions used to determine enrollment.
Additional design details are limited. The official title describes partial blinding, while the masking field indicates triple masking; the registry does not explain this difference or identify the masked roles. It does not provide the randomization procedure, allocation ratio, or endpoint follow-up details beyond the stated 4-week assessment. The population description is also limited to prior treatment failure and SCCHN, without further eligibility characteristics.
Safety reporting is restricted to the listed participant counts, deaths, and a serious-event term. Event timing, duration, severity detail, exposure, and uncertainty are not reported. These gaps mean that the registry can describe the trial structure and selected safety counts, but cannot support a full efficacy or safety interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase 2a Study to Evaluate Suppression of Methotrexate-induced Mucositis by TK112690 — NCT04046250.
- Registry record last updated 2023-08-25; status last verified 2023-08.
- Results first posted 2021-06-03.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a completed, randomized, placebo-controlled phase 2a parallel-group study of TK112690 alongside methotrexate in patients with SCCHN who had failed at least one prior treatment of chemotherapy and/or radiation. Enrollment was 22. The methotrexate schedule was weekly for 4 consecutive weeks, with TK112690 or placebo administered around each methotrexate treatment.
The primary outcome was mucositis at 4 weeks assessed using NCI/CTCAE and WHO scales. Higher scores indicate greater mucositis, and the stated method was to compare scale-specific group means using Student's t-test. The registry record does not report the primary outcome values or analysis results. Safety entries list serious and other adverse events and deaths by group, but do not provide detailed event-level or comparative analyses.