Extension Study of IMO-8400 in Patients With Waldenström's Macroglobulinemia Who Completed Study 8400-401: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extension Study of IMO-8400 in Patients With Waldenström's Macroglobulinemia Who Completed Study 8400-401 (NCT02363439), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

3. Trial Design

This was an extension study of IMO-8400 for patients with Waldenström's Macroglobulinemia who completed Study 8400-401. The registry describes eligibility in terms of completing 24 weeks of IMO-8400 in the preceding study. Its official title further describes the intended population as patients with relapsed or refractory disease. This design therefore concerns continuation into an extension, rather than a newly recruited comparison of treatment groups.

The study is classified as Phase 1 and Phase 2, single-group, and unmasked. Allocation is recorded as NA. The registry lists one IMO-8400 group, with subcutaneous dosing of 0.6 mg/kg/wk or 1.2 mg/kg twice weekly per Protocol 8400-401. It does not describe a separate control group or provide a randomized comparison. The two dosing schedules should not be read as two independently compared arms based on this record.

Enrollment was 5. The study status is completed. The recorded start is 2014-11, and primary completion is 2016-12. These dates establish the registry timeline but do not, by themselves, describe how long each participant received treatment. The primary outcome timeframe is during receipt of study treatment on the trial.

The registry identifies a safety population for the primary outcome. A detailed statistical analysis plan, the process used to select between the listed dosing schedules, and a sample-size justification are not reported in the registry record. The planning assumptions associated with sample-size illustrations are not the trial's own design assumptions; they describe hypothetical equal allocation between two arms, unlike this single-group study.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population

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 population

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over During receipt of study treatment on the trial..

The primary endpoint is the number of participants with adverse events, measured as a count of participants. Its stated purpose is to assess the long-term safety and tolerability of IMO-8400 in patients with Waldenström's Macroglobulinemia. The timeframe is during receipt of study treatment on the trial, and the outcome population is identified as the safety population.

A participant count answers how many people in the defined group experienced an event; it is not a count of all event episodes. A person with multiple events can still contribute as one participant to a count of participants with any adverse event. The registry record does not provide additional detail on event definitions, grading, attribution to treatment, or rules for counting recurrent events.

In general, safety endpoints are used to describe events observed during treatment and to characterize the kinds of harms recorded in a study. Their interpretation depends on the population followed, the time under observation, and how events are defined and collected. Here, the posted safety counts are based on a group of 5 participants, and the record gives no comparator against which to estimate a relative difference. The reported counts therefore describe this group; they do not establish how event frequency would compare with another treatment or with no treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a participant count for its primary outcome, not a continuous measurement or a time-to-event estimate. It identifies the outcome as the number of participants with adverse events and names the safety population as the analysis population. The posted adverse-event data give the number at risk and the number affected in serious and other categories. These are descriptive counts, and no inferential analysis is reported.

What does a participant count represent?

In general, a count of participants with an event records whether each person met the event definition during the relevant observation period. It is distinct from a count of event episodes: repeated episodes in one person do not necessarily represent multiple affected participants. The registry's endpoint description does not state how repeat events were handled or give a detailed operational definition of an adverse event. Those details are not reported in the registry record.

The denominator is important when reading a count. The adverse-event group lists 5 participants at risk. The reported affected counts are 0 for serious adverse events and 4 for the other adverse-event category. These results should remain tied to that recorded group and its safety population. The registry does not provide participant-level data, exposure-adjusted rates, or a breakdown by duration of treatment.

Why is the study design important?

In general, a randomized control group can help distinguish treatment-associated patterns from changes that might occur for other reasons. This study is classified as single-group, with allocation recorded as NA and masking as none. It therefore does not supply a like-for-like control comparison. The adverse-event counts cannot estimate a treatment-versus-control difference, and they should not be interpreted as evidence of comparative effectiveness or safety.

The listed IMO-8400 schedules are part of the single study group in the registry description. The record does not present separate outcome counts for each schedule. It therefore does not support a comparison between the dosing schedules. Any differences between participants receiving different schedules cannot be assessed from the group-level figures reported.

What does the absence of statistical analyses mean?

The registry lists 0 analyses. No p-values, confidence intervals, adjusted estimates, or formal comparisons are reported. In general, a p-value evaluates how compatible data are with a specified null model; it does not measure the size or importance of an effect. A confidence interval describes uncertainty around an estimate under stated assumptions. Neither type of result is available for these counts, so the statistical precision of an underlying event frequency cannot be quantified from the record.

The primary outcome is a count, which is a natural descriptive summary for a small safety population. More elaborate modeling would require decisions about the analysis question, event definitions, observation time, and assumptions. The registry record does not report such a model or analysis plan. No model-based interpretation should be inferred from the counts alone.

How should planning illustrations be interpreted?

In general, power calculations describe the ability of a planned design to detect a specified effect under stated assumptions. They are not a measure of what a completed study actually demonstrated. The assumptions associated with the planning illustrations specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; they also define the target effect as a stated fraction of an observed effect. Those assumptions describe a planning illustration, not the single-group design recorded for this study.

Any sample-size values based on those assumptions are planning illustrations, not observed power and not a reconstruction of the trial's original design. The registry does not report its own sample-size justification. A planning calculation cannot remedy the lack of a comparator, make the observed cohort larger, or show that an effect was detected. The reported counts remain descriptive results from the participants at risk in the extension study.

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("IMO-8400 0.6 mg/kg/wk or 1.2 mg/kg 2xwk")
n      <- c(5)
events <- c(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  IMO-8400 0.6 mg/kg/wk or 1.2 mg/kg 2xwk  5  4  80.0  28.4  99.5  37.6  96.4  35.9  95.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 1 outcome measure and 0 analyses. It does not report a multiplicity adjustment, a hierarchy of hypotheses, or a prespecified plan for selecting among multiple analyses. Multiplicity procedures are generally used when multiple statistical tests create a risk of chance findings; however, no formal statistical tests are reported for this outcome in the registry record. A particular multiplicity approach should not be inferred.

The primary outcome population is the safety population. The registry does not describe the criteria used to define that population beyond naming it, nor does it report a separate efficacy population. The adverse-event group lists 5 participants at risk. The record does not explain whether any enrolled participants were excluded from safety summaries or how membership in the safety population was determined.

Missing-data handling is not reported in the registry record. In general, a count of participants with an event depends on whether participants were observed for the relevant period and how incomplete follow-up is handled. The record does not state whether there were missing event assessments, withdrawals, incomplete exposure, or imputation. No assumption about the absence or treatment of missing data can be made from the posted counts.

The registry also does not describe interim analyses, monitoring rules, or a detailed statistical analysis plan. These details are not reported in the registry record. The available information supports a descriptive reading of the safety counts, but not an assessment of analysis choices beyond the population and outcome description that are recorded.

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 non-serious adverse event terms

The registry reports 0 participants affected by serious adverse events among 5 at risk and 0 deaths. It reports 4 participants affected in the other adverse-event category among 5 at risk. These counts describe the recorded safety group; they are not comparisons with a control group. The serious-event count and the other-event count are separate categories in the posted safety information and should not be combined into a new total.

The registry lists no top serious adverse-event terms. This means no serious-event terms are listed in that summary; it does not provide detail about the broader event profile. The record does not report individual event descriptions, severity grades for the other category, or whether events were considered related to treatment. Those details are not reported in the registry record.

In general, a serious adverse event is a defined safety category, and it is not interchangeable with an event that is merely described as severe. The registry's figures should be read according to its serious-versus-other categories rather than as a complete clinical narrative. The small number of participants also means the counts provide limited precision about event frequency beyond this cohort.

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

The posted results describe adverse events in an extension cohort of 5 participants who received IMO-8400. The registry reports 0 participants affected by serious adverse events, 4 affected in the other adverse-event category, and 0 deaths. These observations apply to the safety population and treatment period described in the record. They provide a descriptive account of recorded events in this cohort.

They do not establish that serious adverse events cannot occur, nor do they quantify a stable event rate for a broader population. A zero count in a small cohort is an observation in that cohort, not proof that the underlying risk is zero. Likewise, the count of 4 in the other category does not, by itself, show how often events would occur under a different treatment or in a different population.

The study was single-group and unmasked, with no randomized control group. It cannot estimate a comparative treatment effect from the reported safety figures. The record also does not provide formal statistical analyses, confidence intervals, or detailed event descriptions. As a result, it cannot support a precise comparison or explain the clinical character of each recorded event.

The extension setting further defines the scope of the evidence: participants were described as having completed Study 8400-401 before entering this study. The findings therefore concern this selected group of prior study participants, not all people with Waldenström's Macroglobulinemia. The reported counts are useful as a record of what was observed in the extension, but they should not be read as a definitive estimate of safety or as a treatment recommendation.

14. Why This Trial Matters Statistically

This study is statistically notable for the narrow, descriptive nature of the evidence it records. It follows patients who completed a preceding study and reports safety counts in a safety population of 5 participants. Such an extension can document events during continued treatment in that group, while its single-group design limits what can be learned about comparative differences.

Counts are direct and interpretable summaries: the registry reports 0 participants with serious adverse events, 4 with other adverse events, and 0 deaths. At the same time, small cohorts offer limited precision. In general, each observed participant has substantial influence on a count when the group is small, and the results may be sensitive to the experience of any individual participant. The registry does not report intervals that would quantify this uncertainty.

The record also illustrates why design and analysis should be read together. A safety count can describe what occurred, but without a comparison group it cannot establish how the count differs from another treatment or from an untreated course. The registry lists no formal analyses, so the evidence presented is descriptive rather than a reported hypothesis test.

Finally, planning assumptions should not be confused with a study's actual design or its observed evidence. The stated illustration assumptions describe a hypothetical two-arm calculation, whereas the trial is recorded as single-group. Recognizing that distinction prevents a planning exercise from being mistaken for observed power or for a result of the extension study. The record's statistical value lies in its defined cohort and safety observations, with the limits of that evidence kept explicit.

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 cohort is small: enrollment was 5, and the adverse-event group lists 5 participants at risk. Counts from this group offer limited precision and cannot characterize uncommon events reliably. No confidence intervals or formal statistical analyses are reported, so uncertainty around an underlying event frequency is not quantified in the registry record.

The study has no randomized control group and is classified as single-group. The record therefore cannot support a like-for-like estimate of differences between IMO-8400 and a comparator. It also does not report separate adverse-event results for the two listed dosing schedules, so those schedules cannot be compared from the posted group-level counts.

The extension population consists of patients who completed Study 8400-401; the record describes completion of 24 weeks of IMO-8400 as the basis for the extension. This limits the scope of the findings to that extension cohort. The registry does not report how many preceding-study participants were eligible, how many did not enter the extension, or how the enrolled participants differed from those who did not continue.

Additional details about event definitions, individual event types, attribution, follow-up duration, exposure, missing data, and handling of repeat events are not reported in the registry record. A detailed statistical analysis plan, interim analyses, and the trial's own sample-size justification are also not reported. These omissions limit interpretation of how safety information was collected and analyzed, and how representative the recorded observation period was for each participant.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Extension Study of IMO-8400 in Patients With Waldenström's Macroglobulinemia Who Completed Study 8400-401 — NCT02363439.
• Registry record last updated 2018-01-09; status last verified 2017-12.
• Results first posted 2017-11-13.
• 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

NCT02363439 is a completed Phase 1 and Phase 2, single-group extension study of IMO-8400 in patients with Waldenström's Macroglobulinemia who completed Study 8400-401. The registry records enrollment of 5, no masking, and no randomized allocation. The listed subcutaneous dosing schedules were 0.6 mg/kg/wk or 1.2 mg/kg twice weekly.

The primary outcome was the number of participants with adverse events during receipt of study treatment, in the safety population. The adverse-event record reports 0 participants with serious adverse events, 4 with other adverse events, and 0 deaths among 5 at risk. The registry lists 1 outcome measure and 0 analyses. No comparator or formal statistical analysis is reported, so these counts are descriptive of the extension cohort.