Arimoclomol in Sporadic Inclusion Body Myositis - Open Label Extension Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Arimoclomol in Sporadic Inclusion Body Myositis - Open Label Extension Trial (NCT04049097), a na phase 3 study. The primary outcome is Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score.

2. Clinical Question

3. Trial Design

This was a Phase 3, open-label, nonrandomized extension trial of arimoclomol in people with sporadic inclusion body myositis who had completed IBM4809. The record lists a single-group model and no masking. Although the stated objective refers to early versus delayed start, the registry does not describe a randomized or like-for-like control comparison. The details needed to understand how any start-time groups were constituted and analyzed are not reported in the registry record.

The recorded enrollment was 121. The listed arimoclomol regimen was 248 mg arimoclomol base, equivalent to 400 mg arimoclomol citrate, 3 times daily. The study began on 2019-05-20, and primary completion was recorded as 2021-11-15. Its status is terminated. The registry says the sponsor terminated the study early and simplified efficacy-endpoint analyses from what had been planned in the protocol; the original statistical plan is not reported in the registry record.

The primary outcome was change in IBMFRS total score from extension-trial baseline to the early termination visit. That visit could occur at a variable time, described as an average of approximately 28 weeks. The primary outcome population was the modified intention-to-treat population with IBMFRS data at that visit. The record says efficacy data were summarized descriptively after early termination. It does not report numerical primary outcome results or an inferential comparison.

Secondary outcomes listed in the record include walking distance, timed mobility, quadriceps muscle strength, hand grip strength, health-related quality of life, and falls or near falls. The registry also lists adverse-event information. These details describe the outcomes selected for assessment, but do not by themselves establish what the results were or whether changes were attributable to arimoclomol.

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: Patients in the modified intention-to-treat population with data for IBMFRS at the early termination visit

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: All patients who received at least 1 dose or partial dose of arimoclomol in IBM-OLE.

6. Primary Endpoint

The registry lists the primary outcome as Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score, measured over Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks)..

The primary endpoint was change in total score on the Inclusion Body Myositis Functional Rating Scale (IBMFRS). It combines 10 areas of function: swallowing, handwriting, cutting food and handling utensils, fine motor tasks, dressing, hygiene, turning in bed and adjusting covers, moving from sitting to standing, walking, and climbing stairs. Each item is graded on a Likert scale from 0, meaning unable to perform, to 4, meaning normal. The summed score ranges from 0 to 40; a higher score represents less functional limitation.

A scale covering several functional tasks can describe how a participant's reported abilities change over the course of an extension trial. The recorded endpoint compares the baseline score in the extension trial with the score at the early termination visit. Because the visit was variable and averaged approximately 28 weeks, the timing of the measurement was not identical for every participant. The record identifies the mean and standard deviation as the summary measures, but does not report the numerical change, its standard deviation, or a confidence interval.

In general, a change score expresses the difference between a participant's follow-up and baseline measurements; its direction must be interpreted using the scale's scoring convention. Here, a higher IBMFRS score means less limitation, but the registry record does not provide the observed change needed to describe the direction or size of the trial's result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

The primary outcome is continuous: IBMFRS is a numerical score, and the registry specifies the mean and standard deviation as summary measures. The mean describes the arithmetic average of the observed scores or changes in the analyzed population. The standard deviation describes how spread out individual observations are around that average. These measures answer different questions: an average change describes the center of the data, while a standard deviation describes participant-to-participant variability. Neither measure is reported numerically for the primary endpoint in the registry record.

In general, a mean can conceal a range of individual experiences. A similar average can arise when participants have broadly similar changes or when individual changes vary considerably. The standard deviation helps describe that spread, but it is not the same as the uncertainty in the mean. A confidence interval is a general way to express uncertainty around an estimated quantity; it gives a range of values compatible with the data and the method's assumptions. A confidence interval for the primary outcome is not reported in the registry record.

What does a change score represent?

The endpoint is change from baseline in the extension trial to the early termination visit. In general, a change score compares a follow-up measurement with that participant's baseline measurement. Its interpretation depends on which direction represents improvement on the scale. For IBMFRS, a higher score indicates less functional limitation. The record does not give the observed change, so it is not possible to state whether the mean moved toward a higher or lower score or how large any movement was.

Change scores also depend on the time between measurements. The registry describes the termination visit as variable, with an average of approximately 28 weeks. In general, when measurement intervals vary, a single mean change can combine observations made over different follow-up durations. The registry does not report whether an analysis adjusted for visit timing or otherwise accounted for differing intervals.

What can descriptive analysis establish?

The record says the sponsor terminated the trial early and simplified efficacy analyses from what the protocol had planned, and that efficacy endpoints were summarized descriptively. Descriptive summaries characterize the recorded data. They can report quantities such as averages and spread without testing a prespecified hypothesis. The registry does not report an inferential test for the primary endpoint, a p-value, or a confidence interval. It also does not report the planned analysis methods or the reason for each simplification.

In general, an inferential comparison asks how compatible the observed data are with a specified statistical model or hypothesis. A p-value is one measure associated with such a test, while a confidence interval conveys uncertainty about an estimate. Neither replaces the estimate itself, and neither establishes that an observed change was caused by a treatment. In this trial, the registry's descriptive-analysis statement and lack of numerical results prevent assessment of the magnitude and precision of the primary outcome.

Why does the design affect interpretation?

The trial is recorded as nonrandomized, open-label, and single-group. In general, random allocation can help make groups comparable on measured and unmeasured characteristics, while a concurrent control can help distinguish changes associated with an intervention from changes that might occur over time for other reasons. Those design features are not present as a randomized control comparison in this record. The stated early-versus-delayed-start objective does not, on its own, show that a controlled comparison was performed.

Open-label status means masking was listed as none. In general, knowledge of treatment assignment can influence participant reports, study conduct, and assessments, depending on the outcome and procedures. This is relevant context for a functional rating scale, but the registry does not describe procedures that might reduce or assess such influences. No claim about the direction or size of any resulting bias can be made from the record.

How should the planning illustrations be understood?

The registry describes sample-size planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These are planning assumptions, not observed trial outcomes. The record states that non-time-to-event illustrations give participants per arm; time-to-event illustrations give a total number of events. Such planning values should not be read as observed power or as proof that a future or completed study had adequate precision.

In general, a planning calculation estimates the information a hypothetical design might require under stated assumptions. Its relevance depends on assumptions such as the target effect, allocation, outcome variability, and analysis method. The registry does not report a numerical primary endpoint estimate here, and the planning assumptions are not a substitute for the actual outcome results. The registry record also does not report a sample-size justification from the study's own design or explain how the planning illustrations relate to the terminated study.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Arimoclomol (Open-label)")
n   <- c(106)
m   <- c(-1.7)
sp  <- c(2.6)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Arimoclomol (Open-label)  106  -1.700  2.600  -2.201  -1.199

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary IBMFRS change outcome and several secondary outcomes, including walking distance, timed mobility, muscle strength, health-related quality of life, and falls or near falls. When a study examines multiple outcomes or multiple comparisons, the chance of obtaining at least one apparently notable result can increase. In general, multiplicity methods may control or describe that issue, but the registry record does not report a multiplicity adjustment or a statistical testing hierarchy. It also states that efficacy analyses were simplified after early termination, without reporting the original analysis plan.

The primary outcome population is defined as patients in the modified intention-to-treat population with IBMFRS data at the early termination visit. That definition indicates that outcome data at the visit were required for inclusion in the primary summary. The registry does not report the number of participants meeting that criterion, the extent or pattern of missing outcome data, or whether any imputation or other missing-data method was used. It is not possible to determine from the registry record whether missingness differed by baseline status or follow-up duration.

In general, missing data can affect both the precision and interpretation of an estimate, especially if the availability of a measurement is related to participants' outcomes. Methods such as imputation or model-based analysis require assumptions that should be described; none are reported. The registry also does not report whether the listed secondary outcomes had separate analysis populations or how missing measurements for those outcomes were handled.

The registry records enrollment of 121, but that enrollment figure should not be treated as the number analyzed for IBMFRS. The analysis-population size and outcome-specific denominators are not reported in 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: corona virus infection (1.7%), transaminases increased (1.7%), pneumonia (0.8%), electrocardiogram abnormal (0.8%), b-cell lymphoma (0.8%).

The adverse-event record lists an open-label arimoclomol group with 121 at risk for serious adverse events and 13 affected. For other adverse events, 121 were at risk and 97 were affected. The record also lists 2 deaths. These are descriptive safety counts; the registry does not report a comparison with a control group or attribute the deaths to treatment. Whether the serious-event and other-event affected groups overlap is not reported in the registry record.

The listed serious adverse-event terms include Corona virus infection and Transaminases increased, each reported as 1.7%; Pneumonia, Electrocardiogram abnormal, B-cell lymphoma, and Intraductal proliferative breast lesion, each reported as 0.8%. These percentages describe the entries as recorded, not comparative risks. The record does not provide event-level details, timing, duration, recurrence, or an assessment of causal relationship. The term list and affected counts alone cannot establish whether an event was caused by arimoclomol or how the observed safety experience compares with what would have occurred without treatment.

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

The registry record documents an open-label extension study of arimoclomol in people with sporadic inclusion body myositis who had completed IBM4809. It identifies IBMFRS change as the primary outcome and describes the scale, the intended observation period, and the analysis population. It also records adverse-event counts and selected serious-event terms. These are useful details about what the study set out to measure and what safety information was entered.

The record does not report the numerical primary outcome result. It therefore does not show the average IBMFRS change, the variability of that change, or its precision. It cannot support a statement about the direction or size of the functional outcome. The record's description of descriptive analyses does not fill this gap because no numerical efficacy summary is reported.

The trial's stated early-versus-delayed-start question also cannot be answered from the design description alone. The registry identifies the study as nonrandomized, open-label, and single-group, and does not report details of a like-for-like comparison or an estimate comparing start times. A stated objective is not evidence that a comparison was conducted or that a difference was found.

In general, changes observed during an extension study can reflect multiple influences, including the passage of time, differences in follow-up duration, and factors other than the intervention. A controlled comparison can help address some of those interpretive challenges, but this registry record does not describe a randomized control comparison. The information recorded cannot establish that a change, if any, was caused by arimoclomol.

The adverse-event information describes events recorded in the open-label group. Without a control comparison and additional details on event attribution and timing, these counts do not establish comparative safety or causality. The registry record supports a description of the study and its recorded safety data, but not a definitive conclusion about efficacy or comparative safety.

14. Why This Trial Matters Statistically

This trial matters statistically because its stated objective and recorded design do not align as a conventional randomized comparison. The study description refers to early versus delayed start, while the registry classifies it as nonrandomized, open-label, and single-group. That distinction matters: an objective to compare groups is not the same as a design that establishes a controlled comparison. The registry does not report the details needed to determine how any early- and delayed-start data were compared.

The primary endpoint is a multidomain functional score, and the registry specifies a change from extension-trial baseline to an early termination visit. The visit was variable and averaged approximately 28 weeks. This makes the analysis population and timing important to interpretation. The record identifies participants with IBMFRS data at the visit as the primary population, but does not report how many were included or how variable follow-up was handled.

The sponsor's early termination and simplification of efficacy analyses are also important. The record says efficacy outcomes were summarized descriptively, but does not provide the planned statistical methods or numerical primary result. Readers therefore cannot assess the magnitude, variability, or precision of the endpoint, nor determine how the simplified analysis differed in practical terms from the planned analysis.

Finally, the registry's planning assumptions should be distinguished from the trial's observed evidence. Planning illustrations based on an observed effect and hypothetical allocation assumptions do not supply a missing outcome estimate or establish observed power. This distinction is useful whenever design calculations appear alongside an early-terminated study with descriptive reporting.

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 most consequential limitation for statistical interpretation is that numerical IBMFRS results are not reported in the registry record. The average change, standard deviation, confidence interval, and any inferential test are therefore unavailable. The record says the efficacy analyses were descriptive, but does not show the resulting primary endpoint summary.

The registry's single-group, nonrandomized, open-label classification limits what can be inferred about the stated comparison of early versus delayed start. It does not identify a randomized control group or explain how start-time groups were defined. No comparative estimate is reported. The registry does not describe masking or other procedures that might address the possible influence of open-label assessment.

Follow-up was variable, with the early termination visit averaging approximately 28 weeks. The record does not provide the distribution of individual follow-up times or say whether timing was incorporated into analysis. It defines the primary population by the availability of IBMFRS data at that visit, but does not report the analysis denominator, missing-data amount, or missing-data method.

The sponsor terminated the study early and simplified efficacy analyses from what had been planned. The protocol's planned statistical methods, any sample-size justification, and the consequences of the change are not reported in the registry record. The registry also does not report a multiplicity strategy for the primary and secondary outcomes. Finally, adverse-event counts are not accompanied by a control comparison, causal assessments, or detailed event timing. These gaps limit conclusions about both efficacy and comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Arimoclomol in Sporadic Inclusion Body Myositis - Open Label Extension Trial — NCT04049097.
• Registry record last updated 2023-09-15; status last verified 2023-08.
• Results first posted 2023-09-15.
• 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 describes a Phase 3, open-label, nonrandomized, single-group extension trial of arimoclomol in people with sporadic inclusion body myositis who had completed IBM4809. The recorded regimen was 248 mg arimoclomol base, equivalent to 400 mg arimoclomol citrate, 3 times daily. Enrollment was 121. The study began on 2019-05-20, had primary completion recorded on 2021-11-15, and is listed as terminated.

The primary outcome was change in IBMFRS total score from extension-trial baseline to a variable early termination visit averaging approximately 28 weeks. The registry says the sponsor ended the study early and simplified efficacy analyses, with efficacy endpoints summarized descriptively. Numerical primary outcome results, analysis denominators, and missing-data methods are not reported in the registry record. The record includes adverse-event counts and selected serious-event terms, but no controlled safety comparison.