Early Phase Human Drug Trial to Investigate Dynamin 101 (DYN101) in Patients ≥ 16 Years With Centronuclear Myopathies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Early Phase Human Drug Trial to Investigate Dynamin 101 (DYN101) in Patients ≥ 16 Years With Centronuclear Myopathies (NCT04033159), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Drug-related Treatment Emergent Adverse Events (TEAEs).

2. Clinical Question

The trial concerns DYN101 in people aged at least 16 years with centronuclear myopathy caused by mutations in DNM2 or MTM1. Its stated aims include assessing safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy. The registry describes the medicine as investigational and states that the study is intended to examine how the drug is distributed and removed from the body, as well as whether there are signs of an effect.

The clinical question is therefore primarily about safety and drug behavior in a small, sequentially treated population, with exploratory attention to preliminary efficacy. Because participants were not randomized to a control arm, comparisons between dose cohorts cannot isolate a treatment effect in the way a randomized controlled comparison can. Differences between cohorts may also reflect their sequence, characteristics or time in the trial. The registry record does not report a control-based estimate of efficacy.

3. Trial Design

This is a Phase 1/2, non-randomized, unmasked, sequential trial of DYN101. The registry lists 14 participants and centronuclear myopathy as the condition. It records the study as terminated. The listed start date is 2020-01-09, and the primary completion date is 2022-06-22. The reason for termination is not reported in the registry record.

The registry summary describes a consent and screening period, a run-in period if applicable, a single-dose treatment part with 4 weeks of follow-up after administration, and a washout period of at least 12 weeks followed by phone calls. It then describes a multiple-dose treatment part involving 12 weeks of weekly dosing and a multiple-dose extension part lasting 12 weeks. The summary states that participants were expected to take part in the single-dose, multiple-dose and extension parts unless they withdrew.

Three dose levels are listed: 1.5 mg/kg, 4.5 mg/kg and 9 mg/kg. Cohort descriptions specify DNM2 and MTM1 subcohorts, with planned cohort composition described separately for each mutation group. The registry notes that the independent data monitoring committee could advise a different dose. The posted serious adverse event information includes single-dose low-dose and middle-dose cohorts, and a multiple-dose low-dose cohort. It does not include corresponding posted counts for every listed cohort and phase.

Non-randomized, unmasked treatment means that there is no randomized allocation to balance prognostic characteristics between groups, and participants and study personnel are not masked to treatment assignment. Sequential dose escalation can support learning about safety and drug exposure across dose levels, but it does not create a concurrent control comparison. The registry record does not report the detailed dose-escalation rules, the timing or contents of committee reviews, or how decisions to move between cohorts were made. It also does not report a protocol-level account of any deviations from the planned sequence.

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: No participant was enrolled in the "Cohort 3 - High Dose" Arm/Group

Single Ascending Dose (Day 1)

Washout Period

Reasons for not completing this period:

Multiple Ascending Dose Period

Reasons for not completing this period:

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Drug-related Treatment Emergent Adverse Events (TEAEs), measured over Baseline until Study termination, up to 28 months.

The primary outcome is the number of participants with drug-related treatment-emergent adverse events (TEAEs), described as being assessed from baseline until study termination, up to 28 months. A TEAE is an adverse event that arises or is recorded after treatment begins; the endpoint further restricts the count to events judged drug-related. The measure is a count of participants with at least one event, not a count of all event episodes or a severity score.

Participant counts are commonly used in safety monitoring because they indicate how many people in the observed group experienced an event meeting the endpoint definition. They can be useful for describing safety in an early-phase trial, where characterizing potential harms and tolerability is a central aim. Such a count does not, by itself, describe when an event occurred, how long it lasted, whether it recurred, or how severe it was. Those details require separate outcome definitions and reporting.

The primary endpoint is not the same as the serious adverse event figures posted for selected cohorts. Seriousness is a separate classification, while the primary outcome is defined in terms of drug-related TEAEs. The record does not report a numerical result for the primary endpoint, its analysis population, or the method used to judge drug relatedness. Consequently, the posted serious-event counts cannot be treated as the primary endpoint result.

For a binary participant-level outcome, the observed count is most informative when its denominator and event definition are clear. The registry supplies cohort denominators for the posted serious adverse event summaries, but it does not report a corresponding denominator and result for the primary TEAE outcome in the information described. The primary endpoint’s numerical result is therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on matching each number to its outcome definition, denominator and study design. The registry describes a participant-level binary endpoint: whether a participant had a drug-related TEAE during the stated observation period. It also posts serious adverse event counts for selected cohorts. These are different summaries, and keeping them separate is essential to avoid treating one as a result for the other.

What does a participant count describe?

A participant count records how many people met an event definition at least once during a specified period. It differs from an event count, which may count repeated episodes in the same person. A count also differs from a rate, which requires an exposure-time denominator, and from a time-to-event analysis, which uses information about when events occur. The primary outcome is explicitly described as a number of participants, so the intended measure is a count rather than an event rate.

Counts need denominators to be interpretable. The serious adverse event summaries give numbers at risk and numbers affected for the listed cohorts. For example, the single-dose low-dose summary reports 3 affected among 6 at risk. This is a descriptive cohort summary, not a causal effect estimate. The primary TEAE outcome’s numerical result and analysis denominator are not reported in the registry record described, so that endpoint cannot be reconstructed from the serious-event summaries.

Why does the study design matter?

Randomization is a method for assigning participants to groups by chance. In a randomized comparison, it can make groups more comparable, on average, with respect to measured and unmeasured factors at the time of assignment. This trial is classified as non-randomized, unmasked and sequential, so it does not have that design-based protection for comparisons among dose cohorts. A difference between groups could reflect dose, participant characteristics, time, treatment sequence or other factors. The registry record does not report an adjustment strategy intended to address such differences.

Sequential cohorts are often useful in early-phase research because safety and drug behavior can be assessed as experience accumulates across dose levels. In general, however, a sequential design is not equivalent to concurrent randomization. Later groups can differ from earlier groups for reasons other than dose, and the absence of masking may influence reporting or assessment. The registry does not report the detailed procedures used to mitigate these risks or the criteria for progression between cohorts.

What would an effect estimate and confidence interval add?

In general, an effect estimate summarizes the size and direction of a comparison, while a confidence interval communicates the range of values compatible with the data under the analysis assumptions. An interval that is wide indicates limited precision; a narrow interval indicates greater precision under those assumptions. These concepts are useful when a study presents a comparison, but the registry information described does not report an inferential comparison, effect estimate or confidence interval for the primary endpoint. The cohort counts alone cannot supply those missing analyses.

Even when a confidence interval is reported, it does not correct for a weak comparison design, unmeasured confounding, incomplete follow-up or an outcome definition that is applied inconsistently. Precision and validity are distinct: a result may be estimated precisely but still fail to answer a causal question if the groups are not comparable. For this trial, the non-randomized sequential design is a central constraint on comparisons across cohorts.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability in count data is greater than a statistical model assumes. If a model assumes less variability than the data contain, standard errors may be too small and confidence intervals too narrow. This matters for outcomes such as repeated event counts, where participants may have different underlying event rates. The posted primary outcome is a count of participants with an event, rather than a repeated event count, and the registry information described does not report a model-based analysis or an over-dispersion assessment. It is therefore not possible to say whether this issue was assessed in the trial analysis.

For a simple binary outcome, the main descriptive information is the number affected and the number assessed. More elaborate analysis may account for design, follow-up or participant characteristics, but the statistical plan and any such methods are not reported in the registry record. The record also does not report a protocol-based sample-size justification. The enrollment figure should not be interpreted as evidence that the study had a particular power to detect an effect.

What can be concluded from the available summaries?

The serious adverse event figures can be read as observed counts among participants at risk in the named cohorts. They do not establish the probability of an event in a broader population, and they do not demonstrate that DYN101 caused or prevented any listed event. A causal interpretation would require a design and analysis that address alternative explanations, as well as complete and clearly defined outcome reporting.

The registry lists no analyses. It does not report the analysis population, missing-data handling, confidence intervals, hypothesis tests, adjusted models or a prespecified statistical analysis plan. Those details cannot be inferred from the endpoint label or from the cohort counts. General statistical concepts explain what such methods could contribute, but they do not establish that the trial used them.

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("Single Dose Cohort 1 - Low Dose", "Single Dose Cohort 2 - Middle Dose", "Multiple Dose Cohort 1 - Low Dose")
n      <- c(6, 8, 6)
events <- c(1, 5, 6)
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  Single Dose Cohort 1 - Low Dose  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Single Dose Cohort 2 - Middle Dose  8  5  62.5  24.5  91.5  30.6  86.3  29.9  86.3
ARM  Multiple Dose Cohort 1 - Low Dose  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, doses, time points or statistical comparisons. In general, testing many questions can increase the chance that at least one result appears noteworthy by chance. Researchers may address this through a prespecified hierarchy, adjustment method or clear separation of confirmatory and exploratory analyses. The registry lists safety, tolerability, pharmacokinetics, pharmacodynamics and exploratory efficacy among the study aims, but it does not report a multiplicity strategy or detailed statistical analysis plan.

The registry identifies one primary outcome measure and lists no analyses. The available information does not establish how many planned comparisons were made, whether any interim analyses occurred, or whether outcome definitions or analyses changed. These details are not reported in the registry record. They should not be inferred from the fact that the trial was sequential or that an independent data monitoring committee is mentioned in the cohort descriptions.

Missing-data handling is also not reported in the registry record. The summary says participants could withdraw and describes follow-up across several treatment parts, but it does not state how missing assessments, withdrawals or incomplete follow-up were handled in the primary analysis. Nor does it report whether the analysis used all enrolled participants, only treated participants, or another population. Without these details, the completeness and potential bias of the endpoint analysis cannot be assessed.

The number enrolled is reported as 14, but enrollment alone does not identify the number contributing data to each outcome. A participant may have contributed to one treatment part without completing every planned part. The registry information described does not report the analysis population for the serious adverse event counts or for the primary endpoint. Therefore, no claim about complete follow-up or an intention-to-treat analysis is warranted.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: covid-19 (16.7%), cholesteatoma (16.7%), breast mass (16.7%), tibia fracture (12.5%), respiratory muscle weakness (12.5%).

The serious adverse event summaries report counts of participants affected and at risk for three named groups: single-dose low dose, single-dose middle dose and multiple-dose low dose. The counts are 3 of 6, 2 of 8 and 0 of 6, respectively. They describe what was recorded in those cohorts; they are not results from a randomized dose comparison.

The registry also lists serious adverse event terms with percentages: COVID-19, Cholesteatoma and Breast mass at 16.7% each, and Tibia fracture and Respiratory muscle weakness at 12.5% each. The information described does not specify the denominator behind these percentages or whether multiple terms could be associated with the same participant. The percentages should therefore be read as listed, not reinterpreted as risks among all 14 enrolled participants.

A serious adverse event is not interchangeable with every TEAE. Seriousness and drug relatedness are separate classifications, and the primary endpoint specifically concerns drug-related TEAEs. The serious-event summaries do not provide the primary endpoint result. The registry reports 0 deaths in each of the three listed groups; these cohort entries do not establish the complete death count across all treatment parts unless that broader accounting is reported.

These small, cohort-specific summaries are descriptive. They do not by themselves establish causation, compare dose safety, or quantify risk in a broader population. The registry record does not report confidence intervals or an inferential analysis for these figures.

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

The posted information gives a limited account of serious adverse events in selected DYN101 cohorts and describes the intended primary safety endpoint. It does not report the numerical result for the primary endpoint, which is the number of participants with drug-related TEAEs. This distinction matters: the available serious adverse event counts cannot stand in for the primary outcome.

The cohort summaries show that serious adverse events were recorded among participants in two single-dose cohorts and that none were recorded among participants in the listed multiple-dose low-dose cohort. These observations describe the specific groups and follow-up represented in the registry entries. They do not establish that dose explains the observed pattern. The trial is non-randomized, unmasked and sequential, with no like-for-like control comparison.

The listed event terms and percentages add descriptive detail, but their denominator is not reported in the registry information described. Without that denominator and clarity about repeated terms within participants, the percentages cannot be interpreted as participant-level risks for the full study population. The registry also does not report confidence intervals for the cohort counts, so their statistical precision is not quantified.

The trial’s stated aims include pharmacokinetics, pharmacodynamics and exploratory efficacy as well as safety and tolerability. The registry information described does not provide numerical results for those aims. It therefore supports no conclusion about a clinical benefit, and no conclusion that DYN101 does or does not work. It also does not establish whether the full planned schedule was completed by each participant or why the study was terminated.

In general, early-phase studies can contribute useful information about treatment exposure and safety patterns, while often being too small or lacking the comparison structure needed for reliable estimates of treatment effects. That general point is relevant to the design, but it does not fill gaps in the posted results. The appropriate reading is descriptive and limited to the specific information reported: enrollment, study design, endpoint definition and selected serious adverse event counts.

14. Why This Trial Matters Statistically

This trial is statistically notable because it combines sequential dose cohorts with a small total enrollment and a safety-focused primary endpoint. Early-phase studies often need to characterize tolerability and drug behavior before later research can address comparative effectiveness. The design and endpoint therefore shape what the observed numbers can answer.

The registry identifies the study as non-randomized and unmasked. That information is crucial when reading cohort counts: a difference across dose groups is not automatically a dose effect. Groups treated at different stages may differ in participant characteristics, follow-up or other conditions. Without random allocation and a concurrent control comparison, those explanations cannot be separated reliably using the counts alone.

The outcome definition also matters. The primary endpoint is a count of participants with drug-related TEAEs, whereas the posted safety figures describe serious adverse events in selected cohorts. Keeping these measures distinct prevents a common interpretive error: using a related but different safety summary as though it were the designated primary result. The primary endpoint result is not reported in the registry record described.

The registry’s listed total enrollment and cohort-specific denominators make clear that the available safety information is limited in scope. Counts from selected groups can identify events observed during the study, but they do not establish how frequently events would occur in a broader population. The term percentages also lack a reported denominator in the information described, limiting their interpretation.

More broadly, this case illustrates why a statistical reading begins with the design, outcome definition and denominator before turning to numerical patterns. A descriptive count can be informative while still being unable to support a causal or comparative claim. The registry’s missing analysis details—including analysis populations and missing-data handling—further constrain conclusions about precision and completeness.

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 registry record marks the study as terminated, but the reason for termination is not reported in the registry record. The information described also does not establish whether termination affected planned follow-up, outcome collection or the availability of results for all enrolled participants.

Although total enrollment is reported as 14, the posted serious adverse event data cover only three named cohort summaries. Corresponding counts for every dose level and treatment part are not included in the information described. The record does not report how many unique participants contributed to each summary, or how participants who entered multiple treatment parts were accounted for.

The primary endpoint is defined, but its numerical result is not reported in the registry information described. The serious adverse event counts are not a substitute because they refer to a different safety classification. The registry does not report the analysis population, the method for determining drug relatedness, or confidence intervals and tests for the endpoint.

There is no randomized control group, and masking is listed as none. These design features limit causal interpretation and can leave assessments vulnerable to differences between cohorts or expectations. Because treatment is sequential, dose groups also do not constitute a like-for-like comparison. The registry does not report adjustment methods that could address those limitations.

The term percentages are listed without a denominator in the information described, and it is not reported whether participants could contribute multiple terms. The registry record also does not report detailed missing-data procedures, sample-size justification, interim analyses or a full statistical analysis plan. These gaps limit assessment of precision, completeness, multiplicity and the robustness of any result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Early Phase Human Drug Trial to Investigate Dynamin 101 (DYN101) in Patients ≥ 16 Years With Centronuclear Myopathies — NCT04033159.
• Registry record last updated 2023-06-27; status last verified 2023-06.
• Results first posted 2023-06-27.
• 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 Phase 1/2, non-randomized, unmasked, sequential trial of DYN101 in participants aged at least 16 years with centronuclear myopathy caused by DNM2 or MTM1 mutations. Total enrollment is listed as 14, and study status is terminated. The described schedule includes a single-dose part, washout and follow-up, weekly multiple dosing for 12 weeks, and a 12-week extension, with participation subject to withdrawal.

The primary outcome is the number of participants with drug-related TEAEs from baseline until study termination, up to 28 months. Its numerical result is not reported in the registry information described. Serious adverse event counts are reported for three selected cohorts: 3 of 6, 2 of 8 and 0 of 6. These are descriptive, non-randomized summaries and do not provide a like-for-like dose comparison.

The record lists no analyses. It does not report the primary endpoint result, analysis populations, missing-data methods, multiplicity strategy, detailed statistical plan or reason for termination. The available information supports a limited description of the design and selected safety observations, not a conclusion about efficacy or comparative safety.