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 Study to Assess Safety and Immune Response of Stage IIB-IV Resected Melanoma After Treatment With MAGE-A3 ASCI (NCT01425749), a randomized early/phase 1 study. The primary outcome is Number of Participants With Treatment-related Adverse Events as a Measure of Safety and Tolerability.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01425749 |
| Phase | EARLY/Phase 1 |
| Condition | Melanoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 25 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Craig L Slingluff, Jr |
| Results posted | Yes |
2. Clinical Question
The study asks whether the administration site for recMAGE-A3 + AS15 is associated with differences in safety and immune response among eligible patients with resected stage IIB–IV melanoma. It compares intramuscular injections with intradermal/subcutaneous injections. The stated aims include assessing treatment-related adverse events and examining immune responses in the injection-site microenvironment, the node draining the vaccine site, and blood.
Population
Eligible patients with resected stage IIB–IV melanoma. The primary outcome population is described as all eligible patients.
Intervention
recMAGE-A3 + AS15 ASCI administered by intramuscular injection in Arm A.
Comparator
The same recMAGE-A3 + AS15 ASCI administered by intradermal/subcutaneous injection in Arm B. This arm required injection-site biopsies at Day 8 and Day 50.
Primary question
How many participants experienced treatment-related adverse events, described as grade 2 events graded by CTCAE v4, over 6 months? The registry record does not provide a single comparative estimate answering this question.
The immune-response questions are broader than a single endpoint. The listed secondary outcomes include MAGE-A3-reactive CD4+ and CD8+ T cells in peripheral blood, antibody responses, dendritic-cell maturation and activation in the sentinel immunized node, and cellular components of the injection-site microenvironment. The record describes these as study objectives, but does not report numerical results for these outcomes. Accordingly, the question addressed by the posted safety counts is not interchangeable with the full set of immunological questions.
3. Trial Design
This is a randomized, parallel-group, early-phase study. The registry lists 25 participants enrolled and identifies two administration-site arms: intramuscular recMAGE-A3 + AS15 in Arm A and intradermal/subcutaneous recMAGE-A3 + AS15 in Arm B. The posted adverse-event figures list 13 participants at risk in Arm A and 12 in Arm B. The record does not describe how the randomization sequence was generated or concealed.
Masking is listed as none. Thus the registry does not report blinding of participants or study personnel. The intervention is a biological product, and the study is described as evaluating safety and preliminary immunological responses. In Arm B, the intervention description specifies injection-site biopsies at Day 8 and Day 50; no equivalent biopsy requirement is listed for Arm A. That difference is relevant when interpreting the procedures and the immune-response objectives, but the record does not state how it was handled in an analysis.
The study condition is melanoma. The recorded start is 2011-06, the primary completion is 2013-07, and the overall status is completed. The phase is EARLY PHASE1. These registry descriptors place the study in an early research setting; they do not, by themselves, establish the precision or completeness of any outcome estimate.
The primary outcome is a participant count for treatment-related adverse events over 6 months, with grade 2 events described using CTCAE v4. The record lists six outcome measures, but reports zero analyses. It does not report a detailed statistical analysis plan, a sample-size justification, or the methods used to compare the arms. The registry record also does not report whether the study used an intention-to-treat, per-protocol, or other analysis population for outcomes beyond the stated primary population of all eligible patients.
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 | Arm A: Intramuscular Injections | Arm B: Intradermal/Subcutaneous Injections |
|---|---|---|
| STARTED | 13 | 12 |
| COMPLETED | 13 | 11 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Arm A: Intramuscular Injections | Arm B: Intradermal/Subcutaneous Injections |
|---|---|---|
| progression of melanoma | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: All eligible patients.
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 | Arm A | Arm B | Total |
|---|---|---|---|---|
| Participants analysed | 13 | 12 | 25 | |
| Age, Continuous | years | 56 (39 to 82) | 54 (40 to 69) | 55 (39 to 82) |
| Sex: Female, Male: Female | Participants | 8 | 5 | 13 |
| Sex: Female, Male: Male | Participants | 5 | 7 | 12 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 13 | 12 | 25 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| 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 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 13 | 11 | 24 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 13 | 12 | 25 |
| Stage of Melanoma: Stage IIIB | participants | 3 | 5 | 8 |
| Stage of Melanoma: Stage IIIC | participants | 5 | 3 | 8 |
| Stage of Melanoma: Stage IV | participants | 5 | 4 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-related Adverse Events as a Measure of Safety and Tolerability, measured over Over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with treatment-related adverse events as a measure of safety and tolerability. The specified timeframe is over 6 months, and the description identifies grade 2 treatment-related events graded by CTCAE v4. The stated population is all eligible patients. This is a participant-count endpoint: it focuses on whether a participant experienced an event, rather than describing the total number of events or the time until an event.
General explanation: in an early-phase study, a safety endpoint helps characterize adverse events observed during treatment and follow-up. A participant count can make the proportion of people affected relevant to the safety question, but a count alone does not describe event severity beyond the endpoint’s stated grading criterion, the number of recurrent events, or when events occurred. Those details require separate reporting.
The registry record does not provide a single primary-outcome comparison between the arms or state which grade categories and time points were combined for a comparative analysis. Its adverse-event summary separately lists serious and other adverse events. Those summary counts should not automatically be treated as the primary endpoint: the primary endpoint specifically concerns treatment-related grade 2 events over 6 months, while the adverse-event summary does not establish that the categories match that definition. The registry record does not report a direct link between those summary figures and the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record establishes the study’s design and aims, and it includes arm-level adverse-event counts. It does not report a primary-outcome estimate comparing the administration sites, a confidence interval, or a statistical test for that endpoint. The record lists zero analyses. Therefore, the posted information does not support a quantified conclusion about the size or precision of a difference between arms on the primary endpoint.
For serious adverse events, the registry summary lists zero affected participants among 13 at risk in Arm A and zero among 12 at risk in Arm B. For other adverse events, it lists 13 affected participants among 13 at risk in Arm A and 12 among 12 at risk in Arm B. These are descriptive counts. The record does not give event terms for serious events, and the list of top serious terms is empty. It also does not specify in this summary whether the other-event counts are restricted to treatment-related events or to grade 2 events. They should therefore not be read as a direct report of the primary endpoint without that qualification.
The trial’s stated scientific aims also include several immune-response outcomes. These concern reactive T cells in blood, antibody responses, dendritic-cell features in the sentinel immunized node, and cell populations at the injection site. The registry record lists these outcomes but does not report their numerical results or arm comparisons. Consequently, the record cannot establish the magnitude, persistence, or type of immune response in either arm from the information available.
General explanation: an estimate is more informative when it is accompanied by an uncertainty interval and a clearly described analysis population. A confidence interval describes a range of values compatible with the data and the statistical model; it does not remove uncertainty or replace clinical and biological interpretation. No such interval is reported for the primary outcome in this record. The arm counts are also small, so the raw counts alone do not establish that the arms differ, or that they are equivalent. No equivalence or non-inferiority objective is reported.
The appropriate reading is limited to what is posted: the registry records no serious events in either arm in its summary and records other adverse events for every participant listed at risk. It does not provide the details needed to connect those figures fully to the primary endpoint or to estimate a comparative treatment effect. No treatment-effect claim should be inferred from these descriptive counts.
9. Statistical Methods Explained
The registry identifies a randomized parallel-group design, a participant-count safety endpoint, and several immunological outcome measures. It does not report the statistical methods used to analyze those endpoints. The explanations below describe general statistical concepts relevant to this design; they are not claims about methods actually used in this study.
What does randomization contribute?
General explanation: random assignment is intended to make the groups comparable, on average, with respect to both measured and unmeasured characteristics at the time of assignment. It supports a causal comparison when allocation is implemented as planned and outcomes are analyzed appropriately. The registry record does not describe sequence generation, allocation concealment, or the analysis population. Randomization alone does not guarantee that the realized groups will be balanced, particularly in a small study, and it does not ensure that follow-up or outcome measurement is free of bias.
What does an unmasked design mean?
The masking field is listed as none. General explanation: when treatment assignment is known, expectations or knowledge of the assigned administration site can influence care, reporting, or assessment. The extent of any such influence depends on the outcome and how it is measured. Some laboratory measurements may be more objective than participant-reported outcomes, but the record does not explain whether outcome assessors or laboratory personnel were masked. The different procedures listed for Arm B, including injection-site biopsies, are also relevant to the context in which outcomes were collected; the record does not report how procedural differences were incorporated into statistical analyses.
How should a participant count be interpreted?
General explanation: for a binary outcome, each participant is classified according to whether the defined event occurred. The resulting count describes the number affected in the population analyzed. Interpreting it requires a clear event definition, observation period, denominator, and analysis population. A participant count is distinct from a count of all event episodes: a person with repeated events may still contribute only once to a participant-level endpoint. The registry describes the primary endpoint as participants with treatment-related adverse events, but does not report a single arm-specific primary-outcome result using that definition.
For comparative inference, investigators may estimate a difference or another contrast between groups and report uncertainty around it. General explanation: a confidence interval conveys the statistical uncertainty around an estimate under the chosen method and assumptions. A wide interval indicates limited precision; an interval that includes values on either side of a null contrast does not establish that the groups are the same. The registry record does not report an effect estimate, confidence interval, or primary-outcome test, so no such interpretation can be made from the posted record.
What is over-dispersion, and is it relevant?
General explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. It can matter for outcomes modeled as counts, especially when participants can experience multiple events or when event counts vary substantially across people. The primary endpoint is described as a number of participants with an event, not a count of repeated episodes. The record does not report event-level distributions or a model, so it is not possible to determine whether over-dispersion was assessed or relevant to an analysis. This general issue should not be confused with the posted participant counts.
What do the planning illustrations represent?
The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These are planning assumptions, not a report of the trial’s original design justification. The registry record does not report the trial’s own sample-size justification or the reasoning behind its enrollment target.
General explanation: planning calculations estimate the sample size needed under selected assumptions about the effect, variability, significance level, and desired power. Changing those assumptions changes the resulting planning requirement. A calculation based on an effect observed in the same study is especially dependent on that observed estimate and should be read as an illustration, not as independent confirmation. Any sample-size figures in this context are planning illustrations, not observed power and not evidence that the trial was adequately powered for its outcomes.
The registry record does not report whether there were interim analyses, adjustments for multiple outcomes, missing-data procedures, or a prespecified model for the immune-response measures. Nor does it state how any repeated measurements or biopsies were analyzed. These omissions limit the ability to reproduce or evaluate the statistical analysis from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The study lists six outcome measures and has several stated immune-response aims, in addition to the safety question. When multiple outcomes are examined, general statistical practice considers the possibility that some apparent findings may arise by chance simply because many questions are tested. Approaches can include prespecifying a primary outcome, controlling a family-wise error rate, or treating secondary findings as exploratory. The registry record does not report a multiplicity strategy or identify how any adjustment would apply across the listed outcomes.
The record identifies a primary safety endpoint, but it does not provide a single primary-outcome comparison or a statistical analysis plan. It lists zero analyses. Details on interim analyses are not reported in the registry record. The record also does not state whether the immune outcomes were analyzed separately, combined into families of hypotheses, or interpreted as descriptive measures. Without those details, the status of any outcome as confirmatory or exploratory cannot be established beyond the labels in the registry.
Missing-data methods are not reported in the registry record. There is no account of missing outcome measurements, losses to follow-up, exclusions after randomization, or how unavailable biopsy, blood, or immune-response measurements were handled. The primary population is described as all eligible patients, but that phrase does not by itself establish whether all randomized participants were included in every analysis or how eligibility and post-randomization events were treated.
These omissions matter because outcomes may have different denominators and different opportunities for missingness. General explanation: a complete-case analysis uses participants with observed data for the outcome in question, while imputation or other methods attempt to account for missing values under stated assumptions. The registry record does not report which, if any, approach was used. No assumptions about missing outcomes, multiplicity, or interim monitoring should be inferred from the posted counts alone.
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 |
|---|---|---|---|
| Arm A | 0 | 13 | 0.0% |
| Arm B | 0 | 12 | 0.0% |
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 |
|---|---|
| Arm A | 13 of 13 |
| Arm B | 12 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A | Arm B |
|---|---|---|---|
| injection site reaction | General disorders | 13 of 13 | 12 of 12 |
| Fatigue | General disorders | 12 of 13 | 12 of 12 |
| Chills | General disorders | 9 of 13 | 4 of 12 |
| Flu-like symptoms | General disorders | 6 of 13 | 7 of 12 |
| arthralgia | Musculoskeletal and connective tissue disorders | 7 of 13 | 4 of 12 |
| myalgia | Musculoskeletal and connective tissue disorders | 5 of 13 | 5 of 12 |
| Fever | General disorders | 4 of 13 | 5 of 12 |
| headache | Nervous system disorders | 5 of 13 | 3 of 12 |
| Nausea | Gastrointestinal disorders | 4 of 13 | 3 of 12 |
| hot flashes | Vascular disorders | 4 of 13 | 2 of 12 |
The posted serious-event summary lists 0 affected participants among 13 at risk in Arm A and 0 among 12 at risk in Arm B. The summary lists no top serious-event terms. For other adverse events, it lists 13 affected participants among 13 at risk in Arm A and 12 among 12 at risk in Arm B. These figures describe participants, not necessarily the total number of event episodes.
The serious-event counts are not the same definition as the primary endpoint, which is described as treatment-related grade 2 adverse events over 6 months. The summary does not state that its other-event counts are limited to treatment-related or grade 2 events. Therefore, the all-participant counts for other events should not be interpreted as the primary endpoint result. The registry record does not report a direct comparison, uncertainty interval, or detail about event timing for these summary categories.
General explanation: zero observed serious events in a study does not establish that the underlying risk is zero. Descriptive counts reflect the participants observed in the study and should be interpreted with the size of the study and the completeness of follow-up in mind. The registry record does not provide enough detail to assess the precision of the serious-event estimates or to determine whether every event was captured in the same way across arms.
12. What the Result Does, and Does Not, Mean
The record describes a randomized comparison of two administration sites for recMAGE-A3 + AS15 and sets out safety and immune-response objectives. Its posted safety summary reports zero serious adverse events among participants at risk in either arm, and reports other adverse events among all participants listed at risk in each arm. These counts are descriptive, and the record does not supply a primary-outcome comparison or uncertainty estimate.
The results do not establish that the two administration sites have the same safety profile. A lack of reported serious events in this summary is not proof that serious events cannot occur, and the other-event counts cannot be assumed to represent the primary endpoint’s treatment-related grade 2 events. The registry record does not report event-level details, comparative estimates, or confidence intervals that would clarify the magnitude and precision of any difference.
The immunological aims include cellular and antibody responses in blood, the sentinel immunized node, and the injection-site microenvironment. However, the record lists outcomes rather than numerical immune-response results. It therefore does not show whether the arms differed in the magnitude, persistence, or type of immune response. The record also does not provide a statistical analysis of those outcomes.
General explanation: a randomized design is intended to support a fair comparison, but the strength of the conclusions depends on outcome reporting, follow-up, analysis methods, and precision. In an early-phase study, descriptive observations may inform later research questions, but they are not by themselves a definitive estimate of comparative effects. The registry record does not state a sample-size justification or report analyses that would establish the precision of the study’s estimates.
Accordingly, the narrow conclusion is that the registry records the stated study design and the listed arm-level safety counts. It does not provide enough reported analysis to determine whether one administration site differs from the other on the primary safety endpoint or the immunological outcomes.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the gap between a clearly described research question and a fully reported comparative result. The registry identifies randomized allocation, parallel arms, an early-phase setting, a safety endpoint, and several immune-response objectives. Those details help readers understand what the investigators intended to study. Yet the record lists zero analyses and does not report a single primary-outcome comparison or the numerical immune-response findings.
The distinction between outcome definition and outcome summary is especially important. The primary endpoint concerns participants with treatment-related grade 2 events over 6 months. The adverse-event summary separately reports serious and other event counts. Without a statement linking these categories to the primary endpoint, the summary cannot stand in for the endpoint merely because both concern safety. Clear definitions, denominators, and follow-up periods are needed to make such an interpretation defensible.
The study also illustrates why arm-level counts and precision belong together. A count can be useful as a description of what was observed, but it does not reveal the uncertainty around a comparison. General explanation: estimates from limited samples can be imprecise, and confidence intervals help readers assess that uncertainty. No comparative estimate or interval is reported for the primary endpoint in the registry record.
Finally, multiple immune outcomes raise questions about analysis priorities and interpretation. The record names several biological measures but does not report a multiplicity strategy or detailed statistical plan. This makes it difficult to distinguish exploratory observations from confirmatory evidence. The statistical lesson is not that the design or measurements are uninformative; it is that transparent reporting of definitions, denominators, analyses, and uncertainty is necessary to translate a study’s aims into interpretable 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 record contains limited information for evaluating the primary endpoint. Although it defines treatment-related grade 2 adverse events graded by CTCAE v4 over 6 months, it does not report a single arm-level result for that endpoint, a comparative estimate, or an uncertainty interval. The separate serious and other adverse-event counts do not specify that they match the primary endpoint’s treatment-related and grade criteria.
The enrollment is 25, with 13 participants listed at risk in Arm A and 12 in Arm B. The registry does not report the trial’s sample-size justification, so the intended precision or ability to detect a difference cannot be assessed from the record. The planning assumptions describe illustrations based on the observed effect; they are not the trial’s own design rationale.
The study is unmasked according to the registry. The record does not say whether outcome assessors or laboratory personnel were masked, or how the different procedures between arms were handled in analyses. Arm B required injection-site biopsies at Day 8 and Day 50, but the record does not report how biopsy availability or any missing immune measurements were addressed.
Further limitations include the absence of a detailed statistical analysis plan, missing-data procedures, multiplicity methods, and information on interim analyses. The record lists multiple immune-response outcomes but does not report their numerical results or analysis methods. It also does not describe randomization sequence generation or allocation concealment. These gaps restrict assessment of bias, reproducibility, and the precision of the safety and immunological findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Assess Safety and Immune Response of Stage IIB-IV Resected Melanoma After Treatment With MAGE-A3 ASCI — NCT01425749.
- Registry record last updated 2016-04-04; status last verified 2016-03.
- Results first posted 2016-04-04.
- 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
NCT01425749 is a completed EARLY PHASE1 randomized, unmasked, parallel-group study in melanoma. It enrolled 25 participants and compared intramuscular with intradermal/subcutaneous administration of recMAGE-A3 + AS15 ASCI. The recorded study start is 2011-06, and primary completion is 2013-07.
The primary outcome is the number of participants with treatment-related adverse events over 6 months, described as grade 2 events graded by CTCAE v4. The registry also lists immune-response outcomes involving MAGE-A3-reactive T cells, antibodies, dendritic cells in the sentinel immunized node, and injection-site cellular components. The posted adverse-event summary lists no serious events among the participants at risk in either arm and lists other adverse events for all participants at risk.
The registry record lists zero analyses and does not report a primary-outcome comparison, numerical immune-response results, a detailed statistical plan, or a sample-size justification. The adverse-event summary counts should not be assumed to equal the primary endpoint because the record does not establish that their definitions match.