Bomedemstat (IMG-7289/MK-3543) in Participants With Myelofibrosis (IMG-7289-CTP-102/MK-3543-002): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bomedemstat (IMG-7289/MK-3543) in Participants With Myelofibrosis (IMG-7289-CTP-102/MK-3543-002) (NCT03136185), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLTs).

2. Clinical Question

The study addressed safety and tolerability alongside steady-state pharmacokinetics and pharmacodynamics. The registry describes a biological rationale in which inhibiting lysine-specific demethylase 1 could affect spleen size, haematopoiesis, and constitutional symptoms. Those aims are not equivalent to the primary endpoint: the named primary outcome is a count of participants with dose-limiting toxicities (DLTs), not a measure of spleen response or symptom improvement.

Because the design had no randomized comparator, it can describe observations during bomedemstat treatment but cannot by itself establish how those observations compare with an alternative treatment or with no treatment. The separate disease and dose groups also should not be read as if they were randomized against one another. Differences between groups could reflect characteristics other than dose, and the registry record does not report an adjusted comparison that would account for such differences.

The primary question is narrowly time-bounded: the DLT definition covers adverse events through Day 7 of the Initial Treatment Period. Other outcomes and safety reporting may concern different periods or event definitions. The endpoint description gives the criteria and who was included in its analysis, but the number of participants with a DLT is not reported in the registry record. Therefore the primary safety question cannot be answered from the endpoint result in this record.

3. Trial Design

This was a Phase 1/2, multicenter, open-label study of bomedemstat in participants with myelofibrosis. The registry lists non-randomized allocation, no masking, and a single-group model. Enrollment was 90. The study began on 2017-07-18, had primary completion on 2022-03-08, and is marked completed.

The study included PMF, PPV-MF, and PET-MF participants. The Phase 1/2a groups received bomedemstat at 0.25 mg/kg/d orally once daily for 85 days during the Initial Treatment Period. Qualifying participants could continue for an additional 85 days during an Additional Treatment Period, as determined by the investigator. The Phase 2b groups received 0.5 mg/kg/d or 0.6 mg/kg/d orally once daily for 169 days during the Initial Treatment Period. The record describes an additional 169-day treatment period for qualifying participants in these groups, with continuation as determined by the investigator. The additional treatment periods could repeat, according to the arm descriptions.

These groups reflect successive study portions, dose levels, and disease subtypes; they are not randomized arms in a controlled comparison. The registry explicitly cautions that the arms are not a like-for-like control comparison. Open-label conduct means masking was absent, so participants and investigators were not blinded to the study treatment. The record does not report a separate control intervention.

The official title identifies safety, steady-state pharmacokinetics, and pharmacodynamics as study aims. The primary outcome listed in the record is the number of participants with DLTs through Day 7 of the Initial Treatment Period. The record lists 10 outcome measures and 0 analyses. A detailed statistical analysis plan, including the methods used for the other outcomes, is not reported in the registry record.

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: Eighteen participants were enrolled in the Phase 1/2a portion of this study and 72 participants were enrolled in the Phase 2b portion of this study.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants receiving at least one dose of bomedemstat were included in the DLT analysis.

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.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose Limiting Toxicities (DLTs), measured over Up to Day 7 of the ITP.

The primary endpoint is the number of participants with dose-limiting toxicities through Day 7 of the Initial Treatment Period. The analysis population is all participants who received at least one dose of bomedemstat. A DLT was an adverse event during the specified period that the investigator considered possibly, probably, or definitely related to bomedemstat and that met one of the listed clinical criteria.

Those criteria include thrombocytopenia leading to clinically significant sequelae, such as a clinically significant bleeding event or the need for prophylactic transfusions; a clinically significant bleeding event with a platelet count >50 x 10^9/L (50 k/μL); any Grade 4 or 5 non-haematologic adverse event; and specified Grade 3 non-haematologic events that did not recover to Grade 2 within 7 days of drug cessation. The definition also lists exceptions for nausea, vomiting, diarrhea, aesthenia, and electrolyte abnormalities.

A participant count is useful in early safety evaluation because it reports how many treated participants met a prespecified toxicity definition during the stated observation window. It is not a complete summary of every adverse event: events outside the definition, outside the window, or not judged related by the investigator are not necessarily captured as DLTs. The registry does not report the observed DLT count, so the endpoint's result and its precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with identifying the kind of design and the outcome being measured. This study is listed as non-randomized, unmasked, and single-group. Its dose and disease-subtype groups are useful for organizing descriptive observations, but they do not form randomized treatment-versus-control comparisons. General statistical principle: random allocation helps balance measured and unmeasured characteristics on average; without it, observed group differences can reflect differences in participant mix, care, timing, or other factors as well as treatment.

What does a participant count convey?

The primary outcome is a count of participants meeting the DLT definition. A count is an absolute description of observed events in the analysis population. To understand how common the event was, a reader also needs the relevant denominator and a clearly defined observation period. The registry specifies the analysis population as participants receiving at least one dose and the DLT window as through Day 7 of the Initial Treatment Period. It does not report the primary count or the number analyzed for that endpoint. Consequently, neither the endpoint frequency nor its precision can be recovered from the endpoint record.

General statistical principle: uncertainty around an event frequency can be expressed with a confidence interval. The interval describes the range of values compatible with the data under the chosen method; it does not remove uncertainty or turn an observational result into a causal comparison. No confidence interval for the primary DLT result is reported in the registry record.

Why does the definition matter?

The DLT endpoint is not a count of all adverse events. It requires an event to occur within the specified period, to meet one of the clinical criteria, and to be considered possibly, probably, or definitely related to bomedemstat by the investigator. The definition also distinguishes event grades and includes stated exceptions. These choices affect which events qualify. Results from a broader adverse-event category therefore cannot be treated as though they were DLT results. Differences in event definitions or observation windows can also make direct comparisons across studies difficult; general interpretation requires alignment of those definitions before comparing frequencies.

The endpoint is reported as a count rather than a time-to-event outcome. General statistical principle: time-to-event methods are designed to use information about when events occur and can accommodate differing follow-up, subject to assumptions about censoring and the model. A simple count does not communicate event timing beyond the endpoint's stated window. The registry does not report a time-to-event analysis for DLTs.

How should the dose groups be read?

The trial includes a Phase 1/2a dose of 0.25 mg/kg/d and Phase 2b doses of 0.5 mg/kg/d and 0.6 mg/kg/d, each represented across disease-subtype groups. Since participants were not randomized between these groups, a raw contrast would be descriptive. General statistical principle: adjustment can sometimes address measured differences, but cannot guarantee removal of confounding, particularly when important factors were not measured or reported. An adjusted statistical plan and adjusted primary endpoint analyses are not reported in the registry record.

The registry notes that simple unadjusted recalculations may be displayed as such and states that the sponsor's own analysis takes precedence if there is a discrepancy. A recalculation from summary data is not the same as a prespecified trial analysis: it may use less detailed information and may not reproduce adjustments, participant-level handling, or the sponsor's analytic choices. In this record, the analysis count is listed as 0, and no primary endpoint analysis is reported. There is therefore no sponsor analysis or recalculated primary endpoint estimate to interpret in the record.

What do planning calculations mean?

General statistical principle: a sample-size calculation is a planning exercise that estimates the number of participants needed to detect a specified effect under stated assumptions. The registry's planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. These assumptions describe an illustration, not the design of this single-group non-randomized trial. The record's instructions distinguish participant counts per arm from total event counts for time-to-event calculations.

Such planning figures are not observed power. Observed power is not a substitute for examining the estimated effect and its uncertainty; after data collection, the estimate and confidence interval are more informative. The registry record does not provide numerical planning results in the study details, and the absence of a randomized comparator means an assumed two-arm comparison should not be read as an actual trial contrast.

Why does over-dispersion matter?

General statistical principle: over-dispersion occurs when variation in count data exceeds what a simple model assumes. If ignored, standard errors can be too small and confidence intervals too narrow. It is relevant to some count outcomes, especially when event rates vary across participants or groups. The primary endpoint is a participant count, but the registry does not report a model for it or a dispersion estimate. No claim about over-dispersion in this study can be made from the record.

Finally, absence of a reported analysis is not evidence of a null result. It means the estimate, uncertainty, and analytic details cannot be evaluated from the registry record. Interpretation should remain limited to the information actually reported: study design, endpoint definition, group descriptions, and the available safety data.

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("Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d", "Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d", "Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d", "Ph 2b PMF: Bomedemstat 0.5 mg/kg/d", "Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d", "Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d")
n      <- c(9, 3, 6, 8, 5, 11)
events <- c(0, 0, 0, 0, 0, 0)
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  Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Ph 2b PMF: Bomedemstat 0.5 mg/kg/d  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6
ARM  Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d  11  0  0.0  0.0  28.5  -0.0  25.9  0.2  26.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and 0 analyses. The primary endpoint is identified, but its result is not reported in the registry record. Results for the other outcomes, the analysis methods used for them, and any hierarchy or gatekeeping procedure are not reported in the registry record either.

Multiplicity arises when several outcomes, groups, time points, or statistical comparisons are evaluated. General statistical principle: conducting many tests can increase the chance of at least one apparently notable result unless the analysis plan addresses that issue. Possible approaches include prespecifying a primary outcome, adjusting significance thresholds, or treating secondary analyses as exploratory. The registry record does not report whether any such strategy was used. It would be inappropriate to infer a multiplicity adjustment or a prespecified testing sequence from the list of outcomes alone.

The record does not report how missing endpoint data were handled, whether participants discontinued before assessment, or whether any imputation method was used. It also does not report the endpoint-specific analysis denominator. The DLT population is defined as participants who received at least one dose, but the number meeting that definition is not stated for the endpoint result. General statistical principle: missingness can affect interpretation when the likelihood of missing data is related to participant condition, treatment exposure, or outcome. Without counts and a missing-data approach, the direction or size of any effect cannot be assessed.

Enrollment is reported as 90, but that figure should not automatically be treated as the denominator for every outcome. Different measures can use different populations and observation periods. The registry record does not report a detailed analysis-population flow or sensitivity analyses for the primary endpoint.

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: abdominal pain (66.7%), nausea (66.7%), thrombocytopenia (63.6%), anaemia (50.0%), gout (50.0%).

The safety record lists serious adverse events by disease subtype and dose group. For each group, it reports the number at risk and the number affected by serious events; deaths are listed separately. These are descriptive group-level figures, not a randomized comparison. The record also lists Abdominal pain and Nausea at 66.7% each, Thrombocytopenia at 63.6%, and Anaemia, Gout, and Arthralgia at 50.0% each among the top serious adverse event terms. The percentage denominator is not reported in the registry record, so these figures should not be converted into a risk estimate for all enrolled participants.

Serious adverse events are distinct from the primary DLT endpoint. The DLT definition is restricted to events through Day 7 of the Initial Treatment Period, requires investigator assessment of possible, probable, or definite relation to bomedemstat, and applies specified clinical criteria. The serious-event counts do not indicate which events met those DLT conditions. The registry does not report a primary DLT count alongside these safety figures.

Deaths are reported in some groups and not others, but the listed counts alone do not identify cause or treatment relationship. The registry record does not report attribution for these deaths in the safety data. Small group-level counts can also be difficult to interpret as stable estimates, particularly without a control group and without consistent follow-up information for each participant.

These figures therefore describe reported safety observations, not proof of causation or a comparison of safety against another treatment. The record does not report a like-for-like control arm.

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

The trial record is informative about how bomedemstat was studied: it identifies the disease subtypes, study phases, dose groups, treatment schedules, and the primary DLT definition. It also reports serious adverse event counts by group and selected serious-event terms. Those details allow readers to understand the design and the scope of the safety reporting.

However, the primary endpoint result itself is not reported in the registry record. The number of participants with DLTs, and the uncertainty around that number, cannot therefore be evaluated. A defined endpoint is not the same as a reported result. Likewise, a completed status and a listed enrollment do not establish what the primary outcome showed.

The design does not provide a randomized control comparison. The dose groups should not be interpreted as a direct test that one dose is safer or more effective than another. They may differ in disease subtype, study phase, participant characteristics, or other factors, and the registry does not report an adjusted comparison. The study's stated aims include pharmacokinetic, pharmacodynamic, and clinical questions, but the primary endpoint is a safety count and does not itself demonstrate changes in spleen size, haematopoiesis, or constitutional symptoms.

The safety counts and serious adverse event terms describe observations recorded in the registry. They do not establish that bomedemstat caused an event, and the listed deaths do not by themselves establish a treatment relationship. Nor do these data establish comparative safety against another therapy, because the record has no randomized control group.

In statistical terms, interpretation is limited by the missing primary result, absent analysis details, non-randomized design, and incomplete reporting of endpoint denominators and missing-data handling. The findings should be described as registry-reported observations, not as a causal estimate or a definitive assessment of benefit and harm.

14. Why This Trial Matters Statistically

This study illustrates why design features must be read alongside outcome definitions. A stated primary endpoint can sound straightforward, but its interpretation depends on the event criteria, attribution rule, observation window, and analysis population. Here, the DLT outcome is limited to a specific early period and a prespecified set of clinical circumstances. It should not be conflated with all adverse events or with the serious adverse event summaries.

The study also demonstrates the distinction between descriptive dose groups and randomized comparisons. Group labels may make a study look like a set of head-to-head dose tests, but this record lists non-randomized allocation and a single-group model. Statistical contrasts between groups would therefore require careful qualification, and the record does not report an adjusted comparative analysis. This matters when readers are tempted to interpret differing counts as a dose response.

Another statistical lesson is that a registry can contain extensive design and safety detail without reporting the result of the primary endpoint. The primary endpoint's definition and analysis population are stated, yet its outcome count is absent. Without that result and its denominator, neither the event frequency nor precision can be assessed. Completion status does not fill that gap.

Finally, safety categories answer different questions. A serious adverse event count, a death count, and a DLT count have distinct meanings and may use different assessment rules. Clear interpretation requires keeping those outcomes separate and avoiding causal claims unsupported by a control group or attribution data. These issues apply broadly to early-phase, non-randomized clinical studies.

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 central limitation for interpreting the primary safety question is that the DLT result is not reported in the registry record. The endpoint definition and analysis population are available, but no count or endpoint-specific denominator is given. This prevents assessment of the observed frequency and precision.

The design is non-randomized, unmasked, and single-group, with no concurrent control arm. The disease-subtype and dose groups are not like-for-like randomized groups, so they cannot support an unqualified causal comparison. The record does not report an adjusted comparison that addresses differences among groups.

The registry lists serious adverse event counts and selected event-term percentages, but does not report the denominator for those percentages. It also does not report attribution for the listed deaths in the safety data. These reporting gaps limit interpretation of the safety figures and prevent a clear assessment of how they relate to treatment exposure or the primary DLT definition.

Further details are not reported in the registry record, including the statistical analysis plan, the handling of missing outcome data, the endpoint analysis flow, and whether or how multiplicity was addressed. The number of outcome measures is listed, but analysis results are not. The available record therefore does not allow readers to check the primary result against a complete prespecified statistical plan or evaluate sensitivity to analytic choices.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bomedemstat (IMG-7289/MK-3543) in Participants With Myelofibrosis (IMG-7289-CTP-102/MK-3543-002) — NCT03136185.
• Registry record last updated 2024-01-10; status last verified 2023-12.
• Results first posted 2024-01-10.
• 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

NCT03136185 is a completed Phase 1/2 multicenter, open-label, non-randomized, single-group study of bomedemstat in myelofibrosis. It included PMF, PPV-MF, and PET-MF participants, with 0.25 mg/kg/d groups in Phase 1/2a and 0.5 mg/kg/d or 0.6 mg/kg/d groups in Phase 2b. Enrollment was 90.

The primary outcome was the number of participants with DLTs through Day 7 of the Initial Treatment Period among participants who received at least one dose. The endpoint definition is described, but the primary result is not reported in the registry record. Serious adverse event counts, selected serious-event terms, and deaths are listed by group; these observations are descriptive and do not create a randomized comparison or establish causation. The record lists 10 outcome measures and 0 analyses.