Single-Dose Study of MT203: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Single-Dose Study of MT203 (NCT02354599), a randomized phase 1 study. The primary outcome is Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE).

2. Clinical Question

3. Trial Design

This was a randomized, single-center, double-blind, placebo-controlled Phase 1 study of single subcutaneous injections of MT203. The registry describes the masking as quadruple and the design model as parallel. The sponsor was Takeda. The study is listed as completed, with start in 2014-11 and primary completion in 2015-05.

The stated purpose was to evaluate safety, pharmacokinetics, and pharmacodynamics in healthy adult Japanese and Caucasian male participants. The intervention descriptions include MT203 doses of 80 mg, 150 mg, and 300 mg, each with matching placebo. Cohort labels distinguish dose groups, and the posted results list Cohort 1-3 placebo separately from Cohort 4 placebo. That distinction matters when reading the safety counts: a count in one placebo group is not automatically a count for the other.

The cohort descriptions identify Japanese and Caucasian participants, but their ethnicity assignments are not fully consistent across the descriptions. In particular, the description attached to Cohort 2's placebo refers to Caucasian participants, while the Cohort 2 active-dose description refers to Japanese participants; Cohort 4 also has Caucasian descriptions. The record therefore does not support reconstructing a complete, unambiguous ethnicity-by-cohort allocation from those descriptions alone.

Randomization can reduce systematic differences between assigned groups, while masking is intended to limit influences on care or outcome assessment. Those design features do not by themselves establish that groups were comparable on every characteristic, especially in a small early-phase study. The registry record does not report the randomization procedure, allocation concealment details, or the identities of the parties covered by the masking label. It also does not report a detailed protocol or a rationale for the enrollment target.

The posted results describe a safety analysis set defined as all participants who received study medication. The record does not report participant flow, withdrawals, or adherence details, so the relationship between randomized participants and the analyzed safety set cannot be further characterized. The available results are counts by listed group; no inferential analysis is posted.

4. Participant Flow and Accounting

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

Before assignment: Healthy Japanese and Caucasian participants were enrolled in the study as 1 of the 4 cohorts Japanese participants in Cohort 1(MT203 80 milligram \[mg\]), Cohort 2 (MT203 150 mg), Cohort 3 (MT203 300 mg) and Caucasian participants in Cohort 4 (MT203 150 mg) to receive MT203, or matching placebo.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety analysis set was defined as all participants who received the study medication.

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: Safety analysis set (SAS) included all participants who received the study medication.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE), measured over Baseline up to Day 85.

The primary endpoint is the number of participants reporting one or more treatment-emergent adverse events, abbreviated TEAEs, from baseline up to Day 85. A participant is counted for this endpoint if they report at least one such event during the stated period. It is a participant-level count, not a count of every event episode: a participant with multiple events still contributes to the endpoint as one participant with one or more TEAEs.

Safety endpoints of this kind are used in early-phase studies to describe adverse events observed after exposure and to identify patterns that may merit further evaluation. They help characterize what was reported during the study period, but a count alone does not describe event severity, duration, timing, or causal relation to study medication. Those details require separate outcome information.

The posted primary results give the number of participants with one or more TEAEs and the participant count in each listed group. For example, the Cohort 1-3 placebo group is reported as 3 participants with an event among 6 participants, while Cohort 1: MT203 80 mg is also reported as 3 among 6. These are counts, not rates or adjusted effect estimates. No confidence intervals or statistical tests for the primary endpoint are reported in the registry record.

The endpoint is limited to the specified observation period. It does not, by itself, capture events beyond Day 85 or establish whether an event was caused by MT203. The registry record does not report a more detailed operational definition of treatment-emergent or an event-collection method.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant-level outcome: whether a participant had one or more TEAEs during the stated period. The registry reports the number meeting that definition and the number of participants in each listed group. Such counts are straightforward to describe, but they do not by themselves provide an estimate of uncertainty or a test of a treatment contrast. No analyses are reported in the registry record.

What does a participant count represent?

A participant with at least one event contributes to the endpoint count, regardless of whether they experienced one event or several. That makes this measure different from an event count, where every episode could contribute. It is also different from an event rate over person-time. The posted data give participant counts; no person-time analysis is reported. Comparing counts without their group denominators would be misleading, which is why both the count and participant number are relevant when reading the results.

General: for binary outcomes, common analyses estimate the probability of the outcome in each group and then compare those probabilities using a risk difference, risk ratio, odds ratio, or another prespecified measure. These measures answer different questions and can behave differently when data are sparse. None of these comparative estimates is reported for the primary outcome in this registry record. No estimate should be reconstructed from the posted counts for this explanation.

Why does small group size matter?

General: with few participants, each observed outcome has a larger influence on a group summary than it would in a much larger study. Estimates can consequently be imprecise, and conventional large-sample approximations may be unreliable when outcomes are sparse. Exact or other small-sample methods may sometimes be considered, but the registry record does not identify a method for comparing these groups. It would not be appropriate to infer which method the sponsor used.

A confidence interval, in general, expresses the uncertainty around an estimate under a specified statistical model. It is not a guarantee that the true value lies within the interval, and its interpretation depends on the design and method. No confidence intervals are reported for the posted TEAE counts. The reader therefore cannot use the registry results to judge the statistical precision of a between-group effect estimate.

What can be said about the planned sample size?

The record lists enrollment of 32, but does not report a sample-size justification or a statistical power calculation for the trial's design. A separate planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a stated fraction of the observed effect. Any such sample-size quantities are planning illustrations, not observed power and not a description of the trial's original design. The registry record does not report the rationale behind the original enrollment target.

General: a sample-size calculation depends on the outcome scale, the effect considered important, variability or event frequency, the statistical test, the significance level, and the desired power. Changing an assumption changes the resulting planning estimate. Retrospective calculations based on an observed effect can be especially unstable because the observed effect itself may be imprecise. They should not be treated as proof that a study was adequately powered or that a result is reliable.

For binary endpoints, a planning calculation also needs an assumed event probability in the comparator group and a defined effect to detect. The record does not report those design assumptions or a formal calculation. A small exploratory safety study may be useful for describing observed events, but its counts are not a substitute for a larger, specifically designed comparison when the goal is to estimate uncommon harms precisely.

Why do group labels and cohorts matter?

The primary results include Cohort 1-3 placebo and Cohort 4 placebo as separate groups. They have separate participant counts and should remain distinct unless a justified analysis specifies otherwise. Combining groups changes the comparison and may obscure differences in cohort composition or study conduct. The registry does not report an analysis that pools the placebo groups. The cohort descriptions also do not align ethnicity assignments consistently, which limits interpretation of any apparent subgroup pattern.

General: a randomized design supports comparison when outcomes are analyzed according to a prespecified strategy that respects random assignment and the trial structure. The registry record does not report the statistical analysis plan, the intended handling of cohort effects, or the adjustment strategy, if any. Therefore, no adjusted treatment effect or dose-response conclusion can be attributed to the posted results.

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("Cohort 1-3: Placebo", "Cohort 1: MT203 80 mg", "Cohort 2: MT203 150 mg", "Cohort 3: MT203 300 mg", "Cohort 4: Placebo", "Cohort 4: MT203 150 mg")
n      <- c(6, 6, 6, 6, 2, 6)
events <- c(3, 3, 1, 1, 1, 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  Cohort 1-3: Placebo  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6
ARM  Cohort 1: MT203 80 mg  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6
ARM  Cohort 2: MT203 150 mg  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Cohort 3: MT203 300 mg  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Cohort 4: Placebo  2  1  50.0  1.3  98.7  9.5  90.5  9.4  90.6
ARM  Cohort 4: MT203 150 mg  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six secondary outcomes spanning pharmacokinetics, pharmacodynamics, and antibody response. These include AUC from time 0 to infinity, AUC from time 0 to time 84 days, maximum observed serum concentration, terminal elimination half-life, plasma total GM-CSF concentration, and the number of participants with a positive anti-MT203 antibody response. Numerical results for these outcomes are not reported in the registry record in the registry record.

When a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently unusual result can increase. General approaches to multiplicity include identifying one primary outcome in advance, adjusting significance thresholds, or treating additional outcomes as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or a family of planned comparisons. No inference about adjustment should be made from the fact that outcomes are listed.

Missing-data methods are also not reported in the registry record. The safety analysis set includes participants who received study medication, but that definition alone does not explain how missing outcome information, withdrawal, or incomplete follow-up was handled. The record does not report the number of participants with missing primary outcome data, reasons for missingness, imputation, or sensitivity analyses. A missing-data plan is relevant because conclusions can depend on whether participants with incomplete follow-up differ from those fully observed.

The registry does not report an analysis population for the secondary outcomes or specify how participants were handled for each assessment. Participant flow, protocol deviations, and analysis rules are not available in the record. These omissions limit assessment of whether results reflect all randomized participants, only those who received study medication, or a different outcome-specific group.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: retinal detachment (16.7%).

The serious adverse-event information reports zero serious events among participants at risk in Cohort 1-3 placebo, Cohort 1: MT203 80 mg, Cohort 2: MT203 150 mg, Cohort 3: MT203 300 mg, and Cohort 4 placebo. Cohort 4: MT203 150 mg reports 1 serious event among 6 participants at risk. These are descriptive registry counts; the record does not report a formal comparison or establish that an event was caused by study medication.

Retinal detachment is listed as a serious adverse-event term with 16.7%. The registry information does not identify the term's participant-level denominator in the registry record, so that percentage should not be converted into a participant count or compared across groups. The record also does not report deaths; the death fields are not populated.

General: a serious adverse event is a classification of seriousness, not a statement that the event was caused by the intervention. Serious events may be rare, and sparse counts provide limited precision. The absence of a reported serious event in a group does not establish that the risk is zero. These figures should be read as the events recorded during the trial, with the available follow-up and reporting, rather than as a complete estimate of longer-term risk.

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

The posted results describe the number of participants with one or more TEAEs in each listed group during baseline up to Day 85. They also give separate serious adverse-event counts. These observations provide a record of events reported in this Phase 1 study, in healthy adult Japanese and Caucasian male participants who received study medication. The results are descriptive and apply to the stated population, interventions, and observation period.

They do not establish whether MT203 caused any particular event. A treatment-emergent event occurs during the defined period after exposure, but timing alone does not establish causation. The primary outcome does not report event severity or relatedness, and the serious-event listing does not replace a causal assessment. The registry record does not report an inferential comparison for the primary outcome, so it does not establish a difference between MT203 and placebo or among dose groups.

The counts also do not establish safety beyond the follow-up described. The outcome window ends at Day 85, and the record does not report longer-term safety follow-up. Rare outcomes are particularly difficult to characterize from small groups; not observing an event in a group is not proof that the event cannot occur. Likewise, a higher count in one listed group does not by itself demonstrate a higher underlying event probability.

This study was designed to evaluate safety, pharmacokinetics, and pharmacodynamics following single subcutaneous injections. The posted primary outcome is about TEAEs, while the listed secondary outcomes include measures of concentration, elimination, GM-CSF, and antibody response. The primary safety counts cannot answer those secondary questions. Their numerical results are not reported in the registry record as.

General: a randomized, masked design can support a fair comparison when the analysis follows the design and uncertainty is quantified. It does not remove the need for sufficient information, transparent outcome definitions, and suitable analyses. Here, no primary-outcome confidence intervals, p-values, or treatment-effect estimates are reported. The findings therefore support a descriptive reading of observed events, not a conclusion that MT203 is beneficial, ineffective, safe, or unsafe.

The evidence is also specific to the enrolled population and dosing context. The registry record describes healthy adult male participants and single-dose administration; it does not establish how findings would apply to other populations, repeated dosing, or different clinical settings. Generalization beyond the study population requires evidence not reported in this record.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the role and limits of early-phase safety data. Its primary outcome uses a clear participant-level count: whether one or more TEAEs were reported during the stated follow-up. Such counts are easy to interpret descriptively and can help characterize what was observed after single-dose exposure. They are not, on their own, precise comparative estimates.

The registry distinguishes placebo groups by cohort. Preserving this structure is important: a control group from one cohort should not automatically be combined with a control group from another, and a contrast across cohorts may reflect more than the intervention alone. The cohort descriptions also have inconsistent ethnicity assignments. Both details illustrate why understanding the study structure is necessary before making statistical comparisons.

The posted results show why event counts need context. A count is meaningful alongside the number of participants in that group, but even counts with denominators do not quantify uncertainty or establish a difference. With small groups, each participant's outcome has substantial influence. Confidence intervals and an analysis suited to the design would help characterize precision; these are not reported for the primary endpoint.

The study also includes several secondary outcomes from different scientific domains. Their presence does not mean that each was analyzed or that a multiplicity strategy was used. The registry lists the outcomes but does not provide their numerical results or report how multiple comparisons were handled. This distinction between outcome registration and result reporting is important when evaluating the scope of the evidence.

Overall, the record illustrates how a randomized, masked design can produce structured safety observations while still leaving key questions about comparative uncertainty unanswered. The counts can inform a descriptive account of events during the trial, but they do not substitute for a prespecified statistical analysis or establish a treatment effect.

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 primary limitation is the sparse information available for assessing comparative safety. The registry reports counts by group but no confidence intervals, p-values, or treatment-effect estimates. Enrollment is listed as 32, while individual result groups are small. These data are therefore limited for estimating uncommon events or differences with precision.

The groups are structured by cohort, with separate placebo labels for Cohort 1-3 and Cohort 4. The registry does not report a pooled comparison or explain whether cross-cohort comparisons were planned. Treating the placebo groups as one control would require assumptions not established by the record. The cohort descriptions also assign ethnicity inconsistently, limiting interpretation of subgroup composition.

The primary endpoint captures participants with one or more TEAEs, not the number of events, their duration, severity, or causal relationship to treatment. Follow-up is stated as baseline up to Day 85. The record does not report information about events beyond that period, detailed event-collection procedures, or the operational definition of treatment-emergent.

The safety analysis set is defined as participants who received study medication, but participant flow and missing-data handling are not reported. The registry does not describe withdrawals, missing primary outcome data, adherence, or sensitivity analyses. It also does not report the statistical analysis plan, sample-size justification, or multiplicity methods.

Six secondary outcomes are listed, but their numerical results are not reported in the registry record in the information available for this account. Consequently, the pharmacokinetic, pharmacodynamic, and antibody findings cannot be evaluated alongside the safety counts. These limitations mean the registry supports a narrow descriptive interpretation rather than a comprehensive assessment of treatment effects or longer-term safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Single-Dose Study of MT203 — NCT02354599.
• Registry record last updated 2016-06-20; status last verified 2016-05.
• Results first posted 2016-06-20.
• 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

NCT02354599 is a completed, randomized, single-center, double-blind, placebo-controlled Phase 1 study of single subcutaneous injections of MT203. The registry lists enrollment of 32 and a study population of healthy adult Japanese and Caucasian male participants. The interventions included MT203 80 mg, 150 mg, and 300 mg, with matching placebo.

The primary outcome was the number of participants reporting one or more TEAEs from baseline up to Day 85, among participants who received study medication. Results are reported as counts by listed group. The registry does not report inferential analyses for this outcome. Six secondary outcomes are listed, but their numerical results are not reported in the registry record as.

The available information supports a descriptive account of observed adverse events. It does not provide a formal comparison, quantify uncertainty around treatment effects, or establish causation.