Exploratory Study of Danicamtiv in Patients With Primary Dilated Cardiomyopathy (DCM) Due to Genetic Variants or Other Causalities: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Exploratory Study of Danicamtiv in Patients With Primary Dilated Cardiomyopathy (DCM) Due to Genetic Variants or Other Causalities (NCT04572893), a na phase 2 study. The primary outcome is Number of Participants With Adverse Events (AEs) in Part A.

2. Clinical Question

The central question is primarily descriptive: what safety experience was recorded during treatment in this exploratory study? The primary outcome is the number of participants with adverse events in Part A. The registry defines an adverse event as a new untoward medical occurrence or worsening of a pre-existing medical condition during a clinical investigation, whether or not it has a causal relationship with study drug. That definition matters because an event recorded during treatment is not, by itself, evidence that the drug caused it.

The population was not restricted to one genetic cause of DCM. The registry describes participants with MYH7 or TTN variants and participants with other causalities, with safety groups also distinguishing genetic and non-genetic DCM. The posted adverse-event results separate groups by study part, dose, and DCM category. Those groups can describe what was recorded in the participating cohorts, but they do not provide a randomized comparison between danicamtiv and a control treatment.

The study also set out to examine preliminary efficacy. Its listed secondary outcomes include changes from baseline in echocardiographic measures such as left ventricular ejection time, stroke volume, ejection fraction, strain, tissue Doppler measures, and end-systolic diameter. The registry record does not report statistical analyses or efficacy estimates for those outcomes. Consequently, the clinical question that can be addressed from the posted results is narrower than the study’s stated aims: the results describe recorded adverse events, while comparative or efficacy conclusions are not available from the registry record.

3. Trial Design

This was a Phase 2a, open-label, exploratory study of danicamtiv in stable ambulatory participants with primary DCM associated with MYH7 or TTN variants or other causes. The registry lists a sequential model, allocation as not applicable, and no masking. Enrollment is listed as 41. These design details describe a study organized around treatment exposure and observation, rather than a randomized, blinded comparison with a control group.

The registry lists danicamtiv as the intervention and uses MYK-491 in the adverse-event group titles. Those titles include doses of 10 mg, 25 mg, 50 mg, and 75 mg twice daily, across Part A and Part B and across MYH7, TTN, genetic DCM, and non-genetic DCM categories. The record does not report enough detail to infer the dose-allocation procedure, rules for moving between doses, or whether participants could contribute to more than one listed group. Those details are not reported in the registry record.

The study started on 2020-08-04, and the registry lists primary completion on 2024-02-22. Its status is terminated. The reason for termination and the timing or circumstances of that decision are not reported in the registry record. The listed enrollment is not the same as a confirmed number treated in every dose and subgroup; the record presents the outcome populations by group, and these should be read as their own reported denominators rather than combined into a newly calculated total.

The study’s stated purpose was to establish safety and preliminary efficacy. Its primary outcome concerns adverse events in treated participants in Part A, while the listed secondary outcomes include echocardiographic changes from baseline. This is an exploratory setting, with no control arm identified for a like-for-like comparison. As a result, observed changes or event counts can describe the enrolled groups but cannot, on their own, separate treatment effects from other explanations such as the course of DCM, background care, or differences between participants.

Several operational details needed to reconstruct the protocol are not reported in the registry record, including the full visit schedule, the exact dose sequence, the planned number of participants in each group, and the reason for termination. The registry record also does not report a statistical analysis plan or inferential analyses. These omissions limit how fully the trial’s conduct and intended comparisons can be evaluated from the record alone.

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: Part B will commence after a participant completes Part A and opts to continue onto Part B. Individual participant doses for Part B will be based on systolic ejection time increase in Part A.

Only the first 6 of 7 groups are shown.

Part A

Reasons for not completing this period:

Part B

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All treated participants in Part A as pre-specified in protocol.

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 Adverse Events (AEs) in Part A, measured over From first dose to 30 days post last dose (Up to approximately 15 weeks).

The primary endpoint is the number of participants with adverse events in Part A. The outcome population is described as all treated participants in Part A as specified in the protocol. The assessment period begins with the first dose and continues to 30 days after the last dose, for up to approximately 15 weeks.

The registry defines an adverse event as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant administered study drug. The definition explicitly says an event does not necessarily have a causal relationship with treatment. Thus, this endpoint captures events occurring in the treatment context; it does not itself determine whether danicamtiv caused them. The endpoint is a participant count, rather than a measure of event severity, duration, or change in cardiac function.

In general, a safety endpoint of this kind is used to describe the types and frequency of medical events observed during exposure and follow-up. Participant counts can help make the safety experience legible, while the accompanying clinical context is needed to understand the nature of events. The registry’s adverse-event results separately list serious and other affected-participant counts by group. Those categories should be read as recorded classifications, not as proof of causation or as a substitute for a detailed clinical review.

The endpoint is not a direct efficacy measure. The registry lists echocardiographic secondary outcomes, including changes from baseline in left ventricular ejection fraction and stroke volume, but statistical results for these outcomes are not reported in the registry record. Therefore, the primary endpoint supports a descriptive account of safety events, not a conclusion about preliminary efficacy.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on what the design can identify and what the registry actually reports. This study is described as open-label, with no masking, allocation listed as not applicable, and a sequential model. The registry also indicates that its arms are not a like-for-like control comparison. These features make the posted event counts useful for describing the observed treatment experience, but they do not provide the randomized contrast normally used to estimate a treatment effect against a concurrent control.

What does a participant count tell us?

The primary endpoint is a count of participants with adverse events in Part A. A participant count answers whether an event was recorded for participants in the specified population and timeframe. It is not necessarily a count of all event episodes: one participant may have more than one event, while the participant endpoint counts people affected. The registry describes the endpoint as a participant count and separately gives affected-participant counts for serious and other adverse events in the safety groups. The record does not provide event-level detail in the information available for this analysis.

The denominator matters. Each adverse-event group lists the number at risk and the number affected, and groups differ in size. Raw counts from groups of different sizes are not directly comparable as measures of risk. Even a rate calculated from those counts would not solve the central design limitation: the groups are not randomized control arms, and the registry does not report an adjusted comparison. No new rates or contrasts are calculated in this explanation.

Why is the comparison structure important?

In general, randomization helps balance both measured and unmeasured participant characteristics across treatment groups. Without a randomized control comparison, observed differences may reflect dose, underlying DCM category, participant characteristics, calendar time, background care, or chance. An open-label design also means treatment assignment is not masked, although the registry does not report how that affected event assessment. These are general statistical considerations, not claims that any particular bias occurred in this study.

The sequential model is recorded, but the registry record does not report the detailed sequence, its decision rules, or the statistical plan for comparing doses. Therefore, it is not possible to assume a particular dose-escalation procedure or infer how decisions were made. Nor can the listed groups be treated as successive steps in a formal dose-response analysis without those details.

How should uncertainty be understood?

In general, an estimate based on a small group is imprecise: the observed count may change substantially in another group of similar size. A confidence interval expresses uncertainty around an estimate under specified assumptions. The registry record does not report confidence intervals or other inferential analyses for the outcomes. The small group denominators and absence of a reported inferential analysis mean that the descriptive counts should not be mistaken for precise estimates of population event risk.

For counts or proportions, statistical methods need to account for the outcome definition, the number of participants, and the study design. If observations are more variable than a model expects, over-dispersion can make conventional uncertainty estimates too narrow; in general, methods that account for over-dispersion can better represent that extra variability. The registry record does not report a model, an over-dispersion assessment, or a method for estimating uncertainty, so there is no basis to say that any particular method was used.

What can the planning illustrations establish?

Any sample-size calculations associated with these results are planning illustrations, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the stated convention is a total number of events; for other outcomes, it is participants per arm. These are generic planning assumptions and do not establish that the trial used them.

In general, sample-size planning asks how much information a future study might need to detect a prespecified effect under chosen assumptions. It does not show the probability that this completed study detected an effect, and it does not change the uncertainty in the observed data. The registry record does not report the trial’s own sample-size justification. It also does not report efficacy estimates or statistical analyses from which a treatment effect can be interpreted. Accordingly, such planning illustrations should not be read as evidence that the trial had adequate power or that an effect was observed.

What is missing from the analysis record?

The registry record lists 28 outcome measures but no statistical analyses. It does not report model specifications, covariate adjustment, handling of repeated measurements, treatment of missing observations, analysis populations beyond the primary endpoint population description, or methods for multiplicity. These details are necessary to assess whether an analysis was prespecified, how robust it might be, and whether outcome findings were selected after results were known. The absence of those details in the registry record is not proof that no analysis was performed elsewhere; it means the record does not document one.

For safety outcomes, descriptive reporting is often central because uncommon serious events can matter even when formal hypothesis testing is not appropriate. However, a descriptive count still depends on definitions, observation time, completeness of follow-up, and consistent recording. The registry provides the primary endpoint definition and timeframe, and posts affected-participant counts for its safety groups. It does not report a detailed account of event adjudication, missing safety follow-up, or exposure-adjusted methods. Interpretation should remain within those stated limits.

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("Part A - MYH7 - MYK-491", "Part A - TTN - MYK-491", "Part A - DCM-Genetic - MYK-491", "Part A - DCM-Non Genetic - MYK-491")
n      <- c(12, 14, 5, 10)
events <- c(9, 9, 4, 4)
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  Part A - MYH7 - MYK-491  12  9  75.0  42.8  94.5  46.8  91.1  46.2  90.9
ARM  Part A - TTN - MYK-491  14  9  64.3  35.1  87.2  38.8  83.7  38.4  83.7
ARM  Part A - DCM-Genetic - MYK-491  5  4  80.0  28.4  99.5  37.6  96.4  35.9  95.7
ARM  Part A - DCM-Non Genetic - MYK-491  10  4  40.0  12.2  73.8  16.8  68.7  16.7  69.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 28 outcome measures, including the primary adverse-event endpoint and secondary echocardiographic outcomes. When a study examines many outcomes, the chance of at least one apparently notable result can increase if each is tested separately. In general, multiplicity procedures can control the overall false-positive risk or clarify which outcomes are confirmatory and which are exploratory. The registry record does not report a multiplicity plan, a hierarchy among secondary outcomes, or adjustments for multiple testing.

The stated study purpose includes preliminary efficacy, and the secondary outcomes include several left ventricular measures. However, no statistical analyses are listed, and efficacy estimates, confidence intervals, and hypothesis-test results are not reported in the registry record. It is therefore not possible to evaluate how the several outcomes were analyzed or whether any efficacy finding was prespecified. The exploratory label is important context, but it does not substitute for a documented analysis plan.

Missing-data methods are also not reported in the registry record. It does not describe the extent or reasons for missing outcome observations, whether participants with incomplete follow-up were included in particular analyses, or how missing echocardiographic assessments were handled. The primary safety endpoint population is described as all treated participants in Part A, but the record does not specify any missing-data procedure for that endpoint.

The analysis populations for outcomes other than the stated primary population are not reported in the registry record. No intention-to-treat or per-protocol definition is listed in the available details, and the record does not explain how participants moving among study parts or dose groups would be handled. These omissions limit assessment of analysis selection and potential bias. They do not establish that data were missing or that analyses were not conducted outside the registry; they mean these procedures cannot be verified from the registry record.

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: cardiac failure congestive (33.3%), arrhythmic storm (25.0%), ventricular fibrillation (25.0%), liver injury (25.0%), urinary tract infection (25.0%).

The serious adverse-event counts are reported by study part, dose, and DCM category. In the listed Part A groups, the serious-event count is 0. In Part B, the record lists 1 affected participant among 4 at risk in the MYH7 50 mg twice-daily group, 1 among 4 in the TTN 50 mg twice-daily group, and 2 among 4 in the TTN 75 mg twice-daily group; it also lists 1 among 3 in the non-genetic DCM 75 mg twice-daily group. The other listed Part B groups have zero serious events recorded. These descriptions retain the group-specific denominators rather than combining them.

The registry lists no deaths in any of the adverse-event groups. It also lists serious-event terms with percentages: cardiac failure congestive at 33.3%, arrhythmic storm at 25.0%, ventricular fibrillation at 25.0%, liver injury at 25.0%, urinary tract infection at 25.0%, and transient ischaemic attack at 25.0%. The registry record does not report the denominator or calculation details behind these term percentages, so they should not be used to infer an event rate for the full enrolled population.

In general, serious adverse events are a subset of safety observations classified by seriousness, while an event’s occurrence during treatment does not by itself establish causality. The reported counts are descriptive, and the small groups do not support reliable comparisons among doses or DCM categories. The registry record does not report adjudication details or a causal assessment for these events.

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

The results mean that the registry documents adverse events among participants in the listed treatment groups, including serious events in some Part B groups and none recorded in the listed Part A groups. The primary outcome concerns participants with adverse events in Part A over the stated period from first dose through 30 days after the last dose, up to approximately 15 weeks. These observations contribute a descriptive account of safety in the study population.

They do not establish that danicamtiv caused any particular event. The registry’s own adverse-event definition says that an event does not necessarily have a causal relationship with treatment. Nor do the counts establish that an event would be more or less common with danicamtiv than without it, because the record identifies no like-for-like control comparison. Group differences may arise for several reasons, and the registry does not report analyses designed to distinguish among them.

The record also does not establish efficacy. The study’s stated aim included preliminary efficacy, and its secondary outcomes include changes in echocardiographic measurements, but no statistical analyses or efficacy estimates are reported in the registry record. Without those results, no conclusion about a change in cardiac function can be drawn from the posted information.

In general, a small exploratory study can identify observations that merit further evaluation, but its descriptive findings do not automatically generalize to a broader population. The group sizes, open-label design, absence of a control comparison, and unavailable analysis details all constrain interpretation. The terminated status adds context, but the reason for termination is not reported in the registry record and should not be inferred from the outcome counts.

The appropriate scope is therefore narrow: the posted results describe adverse-event counts and listed serious-event terms for the study groups. They do not quantify a comparative treatment effect, settle causality, provide a precise population risk estimate, or answer the study’s efficacy question.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between observing events during treatment and estimating a treatment effect. An open-label exploratory study can record safety outcomes across clinically relevant DCM categories and doses. Those observations can describe what occurred in the enrolled groups, but without a like-for-like control group they cannot isolate what would have happened without treatment.

The study also separates participants by genetic and non-genetic DCM categories and reports several dose groups. Such detail may help frame questions for later research, but it creates small subgroups and makes casual cross-group comparisons especially uncertain. A larger count in one group does not automatically mean a higher underlying risk, and a zero count in a small group does not demonstrate that an event cannot occur.

The registry record’s lack of reported statistical analyses is consequential. It lists a broad set of outcomes, including multiple echocardiographic measures, but does not document inferential results, uncertainty estimates, multiplicity handling, or missing-data procedures. Readers therefore cannot determine from the registry record how the efficacy outcomes were analyzed or how much precision any estimated change might have had.

In general, transparent statistical reporting lets readers distinguish descriptive findings from confirmatory evidence. It makes clear which populations were analyzed, how uncertainty was handled, and whether multiple outcomes were considered in a prespecified way. This record provides some design and endpoint definitions but does not supply those analysis details. The distinction is particularly important in exploratory work, where findings are most appropriately treated as descriptive or hypothesis-generating unless supported by a documented comparative analysis.

The study’s status is terminated, but no reason is reported. Statistically, that fact is relevant context rather than an explanation of the results. It cannot be used to infer whether the study ended because of safety, efficacy, recruitment, or another reason. The value of the record lies in the boundaries it makes visible: what was observed in the listed groups and what remains unreported.

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 main trial-specific limitation is the absence of a like-for-like control comparison. The study is open-label, masking is listed as none, and allocation is not applicable. The event counts therefore describe participants receiving danicamtiv in the listed groups, but do not estimate how outcomes differ from a comparable untreated or alternative-treatment group.

The posted groups are small and vary in size. Some Part B groups include only one participant at risk, while other groups contain more; the registry record lists the exact denominators separately. Such variation limits the precision of subgroup descriptions and makes comparisons across doses or DCM categories unreliable. The counts should not be pooled or contrasted as if the groups were randomized.

The registry lists the study as terminated, but the reason for termination is not reported in the registry record. It also does not report the full dose sequence, decision rules for the sequential model, target enrollment by subgroup, detailed follow-up schedule, or whether participants could contribute to multiple groups. Those omissions make it difficult to reconstruct the conduct and intended comparisons.

The registry record lists 28 outcome measures and no statistical analyses. It does not report efficacy estimates, confidence intervals, p-values, multiplicity procedures, missing-data methods, or detailed analysis populations beyond the description of the primary safety population. Although the primary endpoint definition and timeframe are given, event adjudication and detailed safety follow-up completeness are not reported in the registry record.

The serious-event term percentages are posted without denominator or calculation details in the record. They should therefore not be treated as population rates. Finally, enrollment of 41 does not mean every listed subgroup contains the same number of treated participants. Each group’s own reported denominator is the appropriate context for its count.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Exploratory Study of Danicamtiv in Patients With Primary Dilated Cardiomyopathy (DCM) Due to Genetic Variants or Other Causalities — NCT04572893.
• Registry record last updated 2025-05-21; status last verified 2025-05.
• Results first posted 2025-05-21.
• 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

NCT04572893 is a Phase 2a, open-label, exploratory study of danicamtiv in stable ambulatory participants with primary DCM associated with MYH7 or TTN variants or other causes. The registry lists a sequential model, no masking, allocation as not applicable, and enrollment of 41. The study started on 2020-08-04, has a listed primary completion date of 2024-02-22, and is terminated.

The primary outcome is the number of participants with adverse events in Part A, assessed from first dose through 30 days after the last dose, for up to approximately 15 weeks. The posted safety groups list serious and other affected-participant counts across study parts, doses, and DCM categories. No deaths are recorded in the listed groups.

The study’s stated purpose includes preliminary efficacy, and its secondary outcomes include echocardiographic changes from baseline. The registry record lists 28 outcome measures and no statistical analyses. Efficacy estimates, analysis methods, missing-data procedures, multiplicity handling, and the reason for termination are not reported in the registry record. The safety counts are descriptive and do not provide a controlled estimate of treatment effect or establish causation.