Phase II Study to Assess the Safety and Immunogenicity of recMAGE-A3+AS15 ASCI With or Without Poly IC:LC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study to Assess the Safety and Immunogenicity of recMAGE-A3+AS15 ASCI With or Without Poly IC:LC (NCT01437605), a randomized phase 2 study. The primary outcome is Number of Participants With Adverse Events Related to Study Treatment.

2. Clinical Question

The study also set out to assess tolerability and immune response, and to measure tumor return. The brief summary describes an additional interest in tumor return by gene-signature status. The listed secondary outcomes include immunogenicity per treatment arm, relapse-free survival, and median overall survival.

The primary endpoint is a count of participants with adverse events related to study treatment. It is not a direct measure of tumor control or immune response. The registry lists 9 participants in the arm without Poly IC:LC and 5 in the arm with Poly IC:LC, with the recorded primary-endpoint values matching those arm counts.

This page therefore addresses a narrow question about the safety result as recorded. It does not establish a comparative treatment effect: the registry record does not include an estimable two-arm analysis for the binary outcome, and no comparative estimate or uncertainty interval is available. The record also does not report results for the other stated objectives in the registry record.

3. Trial Design

This was a randomized, parallel-group Phase II study. One arm received recMAGE-A3 + AS15 ASCI injections without Poly IC:LC; the other received the same ASCI injections with Poly IC:LC. The trial was unmasked, meaning the registry describes no masking. The registry does not report further details about how randomization was implemented or whether any stratification was used.

The official title describes the intended population as patients with resected MAGE-A3-positive stage IV melanoma. Melanoma is the listed condition. The record reports enrollment of 14 participants. The arm results list 9 participants in the arm without Poly IC:LC and 5 in the arm with Poly IC:LC. These are the recorded arm sizes; the registry information does not explain the allocation process or the reason for the difference in those sizes.

The study began on 2011-10-11, had a primary completion date of 2018-07-18, and is listed as terminated. The reason for termination is not reported in the registry record. The primary endpoint’s timeframe is described as beginning of treatment to end of follow-up, up to 5 years per participant. This does not mean that every participant was observed for the full stated period; individual follow-up durations are not reported in the registry record.

The study’s stated aims went beyond adverse events. They included immune response and tumor return, with relapse-free survival and overall survival among the listed secondary outcomes. The registry information does not provide detailed protocol procedures, follow-up schedules, or an account of which participants contributed data to each outcome. Those design details are not reported in the registry record.

Randomization establishes the intended comparison between the two treatment strategies, but the posted information does not support a full assessment of how that comparison was carried out or analyzed. In particular, the registry record does not report an analysis population definition, a statistical analysis plan, or a reason for the study’s terminated status. The accompanying tables and plots should be read as descriptions of the posted data, not as substitutes for these missing design and analysis details.

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

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.

Population: All participants enrolled on study. All participants who received study treatment. Outcome Measures: All participants evaluable at time of analysis.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events Related to Study Treatment, measured over Beginning of Treatment to End of Follow Up - up to 5 years per participant.

The primary endpoint counts participants with adverse events related to study treatment. Its stated timeframe runs from the beginning of treatment to the end of follow-up, up to 5 years per participant. The endpoint description refers to adverse events after receiving a dose of recMAGE-A3 + AS15 ASCI, either alone or in combination with Poly IC:LC.

A participant count is a way to summarize how many people in an arm experienced the specified outcome. It can make a safety result easy to read, but it does not describe the type, severity, duration, or timing of every event. Those details are not part of the primary endpoint’s reported count. Nor does the count, by itself, show whether an event was caused by treatment; the endpoint is defined as treatment-related, while the event-assessment procedures are not reported in the registry record.

Safety endpoints are used to describe the adverse events recorded during a study and to support comparisons between treatment groups when the data and analysis permit. Here, the recorded values are 9 in the arm without Poly IC:LC and 5 in the arm with Poly IC:LC, alongside arm sizes of 9 and 5. These counts are the posted primary-endpoint values. They do not provide a comparative estimate with an uncertainty interval, and they should not be treated as an adjusted analysis.

The study also names immune response and tumor-return outcomes, but those measure different aspects of the study than the primary safety count. The endpoint should therefore be interpreted on its own terms: it records the number of participants with related adverse events, rather than measuring immune response, relapse-free survival, overall survival, or treatment benefit.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is described as randomized, unmasked, and parallel group. These terms describe different parts of the design. Randomized means participants were assigned to treatment groups by a random process, according to the registry description. Parallel group means participants were assigned to one treatment arm rather than crossing between the two arms. Unmasked means the record describes no masking. Details of the randomization procedure, allocation concealment, and who knew each participant’s assigned treatment are not reported in the registry record.

What does a participant count show?

The primary outcome is a count of participants with adverse events related to study treatment. A count is the number of people who meet the endpoint definition. It is not the same as a count of all adverse-event episodes: a participant with more than one event may still contribute once to a participant-based outcome. The endpoint is explicitly defined in terms of participants, but the registry record does not provide event-level data or additional rules for combining events.

The recorded primary values are 9 and 5, with arm sizes of 9 and 5. These values are descriptive summaries. A comparison between arms would ordinarily need to specify an effect measure and quantify its uncertainty. For a binary outcome, an analysis might compare the probability of an event between arms; however, the registry does not report an estimable two-arm comparison. No comparative estimate, confidence interval, or p-value is reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval describes the uncertainty around an estimated quantity under the assumptions of the analysis. It shows a range of values compatible with the observed data and method; it is not a guarantee that the true value lies within that range. No confidence interval is available for the primary comparison in the registry information. Without an interval, readers cannot assess the precision of a between-arm estimate from the posted results.

In general, a p-value evaluates how compatible the data are with a specified null hypothesis under a statistical model. It does not measure the size or importance of an effect, and it does not establish causation by itself. The registry record does not report a p-value for the primary two-arm comparison. The absence of an analysis result should not be interpreted as evidence of no difference.

What do the safety categories represent?

The safety summary distinguishes serious adverse events, other adverse events, and deaths. These categories should be read as separate reported summaries. The serious-adverse-event figures are 3 affected among 9 at risk in the arm without Poly IC:LC, and 1 affected among 5 at risk in the arm with Poly IC:LC. For other adverse events, the record lists 9 affected among 9 at risk and 5 affected among 5 at risk, respectively. Deaths are listed as 4 and 2. The registry information does not clarify how the death entries relate to adverse-event attribution or whether they occurred during the same observation period as the other safety summaries.

The listed serious adverse-event terms include percentages, but the denominator and calculation method are not described in the information. General statistical guidance is to avoid interpreting a percentage as an incidence proportion unless its denominator and unit are clear. The percentages should therefore be read as the posted term-level figures, not converted into arm-specific risks or counts.

What does the missing comparison mean?

The registry’s analysis information indicates that a two-arm comparison was not estimable for the binary outcome. This is different from a reported comparison that found no evidence of a difference. It means the registry information does not supply the requested comparative analysis. No unadjusted recalculation is presented because there is no reported comparative estimate to describe, and no sponsor analysis is available in the summarized details to take precedence over a recalculation.

In general, randomization can help make treatment groups comparable on average, but it does not guarantee that all measured or unmeasured characteristics are balanced in a particular trial. A careful interpretation also depends on knowing the analysis population, handling of missing outcomes, and analysis plan. These details are not reported in the registry record. The total enrollment and the arm counts are available, but the record does not explain whether all enrolled participants were included in every outcome analysis.

The registry states that the primary endpoint timeframe extends from beginning of treatment to the end of follow-up, up to 5 years per participant. In general, differences in follow-up duration can affect the opportunity to observe events. The record does not provide individual follow-up times or explain how varying follow-up was handled in the primary count. This matters when interpreting a cumulative count over a follow-up period, especially alongside outcomes such as relapse-free survival or overall survival, for which timing is central.

Finally, the registry lists three secondary outcomes, but their quantitative results and analysis methods are not included in the information. The study’s objectives also mention gene-signature subgroups, but subgroup definitions and results are not reported in the registry record. These limits mean the available data support a description of recorded counts, not a complete evaluation of the planned clinical and immunologic questions.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("A: recMAGE-A3 + AS15", "B: recMAGE-A3 + AS15 + Poly IC:LC")
n      <- c(9, 5)
events <- c(9, 5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  A: recMAGE-A3 + AS15  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7
ARM  B: recMAGE-A3 + AS15 + Poly IC:LC  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6

11. Multiplicity, Missing Data and Analysis Populations

The study lists several objectives and outcomes: treatment-related adverse events as the primary endpoint, as well as immunogenicity, relapse-free survival, and overall survival among the secondary outcomes. The brief summary also describes tumor-return assessment by gene-signature status. When a study examines multiple outcomes or subgroups, multiplicity becomes relevant: in general, testing many questions can increase the chance of at least one apparently notable result by chance. Whether and how to address that issue depends on the prespecified analysis plan. The multiplicity strategy is not reported in the registry record.

The record does not report a statistical analysis plan, a hierarchy among secondary outcomes, or whether any adjustment for multiple comparisons was planned. It also does not provide the quantitative results or analysis methods for the listed secondary outcomes in the information. Consequently, this page cannot determine whether the study’s multiple questions were handled as confirmatory or exploratory analyses.

Missing-data handling and analysis populations are also not reported in the registry record. The arm sizes and primary endpoint counts are listed, but the record does not explain how missing outcome information, withdrawals, or participants with incomplete follow-up were handled. It does not state whether analyses used all randomized participants, only participants who received treatment, or another defined group. These distinctions can affect interpretation, particularly when safety or time-to-event outcomes are involved.

The registry lists the study as terminated, but the reason is not reported in the registry record. The record does not say whether termination affected follow-up, outcome collection, or the planned analyses. These gaps prevent assessment of potential attrition, deviations from the intended analysis, or selective outcome reporting. They should be treated as unanswered questions, rather than filled in with assumptions about the protocol or conduct.

12. 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: atrial fibrillation (20.0%), infections and infestations - other, specify (11.1%), respiratory, thoracic and mediastinal disorders (11.1%), thromboembolic event (11.1%), central nervous system necrosis (11.1%).

The safety summary reports serious adverse events separately from other adverse events and deaths. In the arm without Poly IC:LC, it lists 3 participants affected by serious adverse events among 9 at risk, 9 affected by other adverse events among 9 at risk, and 4 deaths. In the arm with Poly IC:LC, it lists 1 participant affected by serious adverse events among 5 at risk, 5 affected by other adverse events among 5 at risk, and 2 deaths. These are the posted entries, not a formal comparison between arms.

The terms marked as the top serious adverse events include Atrial Fibrillation at 20.0%, Infections and Infestations - Other, Specify at 11.1%, Respiratory, Thoracic and Mediastinal Disorders at 11.1%, Thromboembolic Event at 11.1%, and Central Nervous System Necrosis at 11.1%. The registry information does not give the denominators or clarify whether these percentages refer to participants or events. They should not be treated as arm-specific percentages or converted into counts.

Serious adverse events, other adverse events, and deaths are different categories; one should not assume they are mutually exclusive or add them together. The record does not provide the event-level details, attribution rules, timing, or exposure-adjusted analyses needed for a fuller safety interpretation. These figures describe what the registry lists, without establishing a causal relationship or a comparative safety effect.

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

The posted data document treatment-related adverse-event counts in a randomized Phase II study of recMAGE-A3 + AS15 ASCI with or without Poly IC:LC. The primary endpoint values are 9 in the arm without Poly IC:LC and 5 in the arm with Poly IC:LC; the arm sizes are 9 and 5. The safety summary also records serious adverse events, other adverse events, deaths, and several serious-event terms. These results give readers a description of the entries recorded for the study.

They do not establish that one treatment strategy has a higher or lower adverse-event risk than the other. The registry record does not include an estimable two-arm analysis for the primary binary outcome, and no comparative estimate or confidence interval is reported. Counts alone do not quantify the precision of a difference. Nor do the posted summaries establish that any particular event was caused by treatment.

The results also do not answer whether the treatment combinations produced an immune response or changed tumor return, relapse-free survival, or overall survival. These were among the study’s stated objectives or listed secondary outcomes, but quantitative results for them are not included in the information. The gene-signature question in the brief summary cannot be evaluated from the registry entries on this page.

In general, a randomized design is intended to support comparisons between assigned groups, but interpreting a result still requires the relevant outcome data, a clearly defined analysis, and an assessment of uncertainty. Here, the registry describes a small study with 14 participants and reports a terminated status. The reason for termination and the details of outcome follow-up are not reported in the registry record. Those limitations should temper any broader conclusion drawn from the counts.

The most defensible reading is therefore descriptive and bounded: the registry records the stated adverse-event counts and safety summaries, but the information cannot establish comparative effects or resolve the study’s other clinical and immunologic questions. It is not a basis for medical advice or an individual treatment decision.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction between reporting arm-level counts and reporting a comparative statistical result. The registry gives a primary endpoint count for each treatment arm, but it does not provide an estimable two-arm analysis. A table can make the counts easy to inspect; it cannot, on its own, tell readers how precise a treatment contrast would be or how compatible the data are with different possible effects.

The study also shows why endpoint definitions and denominators matter. The primary endpoint counts participants with treatment-related adverse events, while the safety summary separately lists serious adverse events, other adverse events, deaths, and serious-event terms. These summaries answer different descriptive questions. The term-level percentages lack a stated denominator in the information, so interpreting them as participant-level risks would go beyond the record.

Randomization is a valuable design feature, but it does not replace transparent reporting of the analysis population, missing-data approach, follow-up, and statistical plan. Those details are not reported in the registry record. Their absence limits assessment of how the recorded data relate to the original study objectives and how robust any intended comparison might be.

The study’s aims also span safety, immunogenicity, and tumor outcomes. Looking across multiple questions raises general issues of multiplicity and interpretation, especially when results are not accompanied by a stated analysis hierarchy. The registry record does not report how multiplicity was addressed. This is a useful reminder that a list of outcomes is not itself evidence that each outcome has a reported, interpretable result.

Statistically, the trial matters as an example of how to read registry results cautiously: distinguish descriptive summaries from inferential comparisons, keep each endpoint’s definition in view, and identify where the record leaves uncertainty unresolved. The posted results support a limited account of safety counts, not a complete analysis of the study’s broader questions.

15. 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 posted enrollment is 14, with 9 participants in the arm without Poly IC:LC and 5 in the arm with Poly IC:LC. These limited arm sizes mean that the counts should not be mistaken for precise estimates of comparative risk. The registry does not provide a confidence interval or an estimable two-arm analysis for the primary binary outcome, so the precision of any between-arm difference cannot be assessed from the information.

The trial is listed as terminated, but the reason is not reported in the registry record. The record does not explain whether termination affected recruitment, follow-up, outcome collection, or the planned analysis. The primary timeframe is up to 5 years per participant, but individual follow-up duration and the handling of different follow-up times are not reported.

Although the trial is described as randomized, details of randomization and allocation are not reported in the registry record. The study is unmasked; the consequences of that design for event assessment cannot be assessed without further information about how adverse events were collected and attributed. The registry also does not report an analysis population, missing-data procedures, or protocol deviations.

The primary endpoint counts participants with treatment-related adverse events, but the available summary does not describe event severity, timing, duration, or event-level frequency. The serious adverse-event terms have percentages without a denominator explained in the information. The death entries do not include details about timing or relationship to treatment.

Finally, the registry lists immunogenicity, relapse-free survival, and overall survival among the secondary outcomes, but their quantitative results and analysis methods are not included. The gene-signature subgroup objective also lacks reported subgroup definitions and results. These limitations prevent a complete assessment of safety, immune response, and tumor outcomes from the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Study to Assess the Safety and Immunogenicity of recMAGE-A3+AS15 ASCI With or Without Poly IC:LC — NCT01437605.
• Registry record last updated 2019-12-20; status last verified 2019-12.
• Results first posted 2019-12-20.
• 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.

19. Record Summary

The registry record describes a randomized, unmasked, parallel-group Phase II study in patients with resected MAGE-A3-positive stage IV melanoma. It compares recMAGE-A3 + AS15 ASCI injections without Poly IC:LC against the same ASCI injections with Poly IC:LC. Enrollment is listed as 14, and the study status is terminated.

The primary endpoint is the number of participants with adverse events related to study treatment, from the beginning of treatment to the end of follow-up, up to 5 years per participant. The recorded values are 9 in the arm without Poly IC:LC and 5 in the arm with Poly IC:LC, with arm sizes of 9 and 5. The record does not include an estimable two-arm analysis for this binary outcome.

The study also lists immunogenicity, relapse-free survival, and overall survival outcomes. The registry record does not include quantitative results for those outcomes. The reason for termination, detailed statistical methods, missing-data handling, and analysis populations are not reported in the registry record.