A Study of Diroximel Fumarate (DRF) in Adult Participants From the Asia-Pacific Region With Relapsing Forms of Multiple Sclerosis (RMS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Diroximel Fumarate (DRF) in Adult Participants From the Asia-Pacific Region With Relapsing Forms of Multiple Sclerosis (RMS) (NCT05083923), a na phase 3 study. The primary outcome is Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs).

2. Clinical Question

The study asks about safety and tolerability during treatment with diroximel fumarate (DRF) in adults with relapsing forms of multiple sclerosis (RMS) from the Asia-Pacific region. Its stated objectives focus on adult East Asian participants: safety and tolerability through 24 weeks in Part 1 and through 48 weeks in Part 2. Part 1 also evaluates the pharmacokinetics of DRF metabolites in a subset of participants.

Because all participants receive DRF and there is no control group, the results describe events observed during treatment in the study cohorts. They do not estimate a treatment effect relative to another therapy or to no treatment.

3. Trial Design

The registry identifies this as a Phase 3, open-label, single-arm, multicenter study. It lists an enrollment of 136 and a completed status. The recorded start date is 2021-11-18, and the primary completion date is 2024-09-11. The registry describes the intervention as DRF and identifies cohorts of Japanese and Chinese participants.

The dosing description starts with DRF 231 mg oral capsules twice daily from Day 1 through Day 7. From Day 8, participants are scheduled to receive DRF 462 mg oral capsules twice daily up to Week 48. No randomized allocation or masking is listed. The study therefore does not include a like-for-like control group, and the country cohorts should not be interpreted as randomized treatment arms.

The primary outcome concerns treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs), with the Part 1 timeframe stated as Baseline (Day 1) up to Week 24. For participants who prematurely discontinue, adverse events were reported up to 2 weeks post discontinuation. The registry also describes a Part 2 safety objective through 48 weeks and a Part 1 pharmacokinetic objective in a subset of participants.

The record lists secondary pharmacokinetic outcomes for plasma concentrations of monomethyl fumarate (MMF) and 2-hydroxyethyl succinimide (HES), as well as maximum observed concentrations and areas under the concentration-time curve. The registry does not report a randomized comparison, and the study design does not support a direct comparative estimate between DRF and another treatment.

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: Total of 136 participants diagnosed with relapsing forms of multiple sclerosis (RMS) were enrolled in this study. Of these, 102 participants received study treatment. Study consists of 2 parts: Part 1 (Day 1 to Week 24) and Part 2 (Week 24 to Week 48).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analysis set included all participants who had received at least 1 dose of study treatment.

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 analysis set included all participants who had received at least 1 dose of study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs), measured over Baseline (Day 1) up to Week 24 (for prematurely discontinued participants, AEs were reported up to 2 weeks post discontinuation).

The primary outcome counts participants with TEAEs and TESAEs during the stated Part 1 observation period. The registry defines an adverse event as an unfavorable and unintended sign, symptom, or disease temporally associated with use of the study product, whether or not related to it. An event is treatment-emergent if it starts or worsens on or after the first dose through 1 day after the last dose, or through completion of the safety follow-up visit where applicable. TEAEs include both serious and non-serious events.

An SAE is defined by its consequences or clinical importance: it results in death, is life-threatening, requires inpatient hospitalization or prolongs an existing hospitalization, causes significant disability or incapacity or a congenital anomaly, or is otherwise medically important. These definitions distinguish seriousness from whether an event is considered related to treatment.

Counting participants with events is a direct way to describe the frequency of observed safety events in a treated group. It gives a reader the number of participants affected, but does not by itself describe event duration, severity beyond the serious classification, recurrence, or causal attribution. The registry does not report an adjusted safety estimate or a comparator-based effect for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a count of participants with TEAEs and TESAEs. The registry identifies the analysis population as the safety analysis set: all participants who received at least 1 dose of study treatment. It describes the observation window as Baseline (Day 1) up to Week 24 for the primary outcome, with adverse-event reporting up to 2 weeks post discontinuation for participants who prematurely discontinued.

What does a participant count describe?

A participant count describes the number of people in a defined analysis population who meet an event definition during an observation period. It is a useful descriptive measure for safety because it makes clear how many participants were affected. The count depends on the population included, the event definition, and the period in which events are collected. Those details matter when interpreting the count: an event outside the specified period or an event not meeting the recorded definition may not be represented in the endpoint.

General statistical explanation: counts are not the same as event rates over time. A count does not account for differences in how long participants were observed, unless the analysis explicitly incorporates time at risk. The registry reports a defined follow-up period and an adjustment to adverse-event reporting after premature discontinuation, but it does not report a time-to-event analysis for the primary endpoint.

Why distinguish TEAEs from TESAEs?

The registry treats TEAEs as events that start or worsen after treatment begins within the defined treatment-emergent window. It includes both serious and non-serious TEAEs. TESAEs are the subset classified as serious using the registry's listed criteria. Seriousness refers to the event's consequences or medical importance; it is separate from whether investigators consider the event related to the study product. This distinction is important because an event can meet the timing definition for a TEAE without being attributed to treatment, and seriousness alone does not establish causality.

What can an open-label, single-arm study estimate?

General statistical explanation: a single-arm study can describe outcomes observed among participants who receive the intervention. Without a concurrent comparison group, the study cannot directly separate events associated with treatment from events that might also occur because of the underlying condition, other circumstances, or background risk. Open-label status also means masking is not listed; the registry does not report a blinded assessment for the primary safety outcome.

The Japanese and Chinese cohort counts provide a descriptive view of the recorded safety outcome in those cohorts. They are not randomized groups. General statistical explanation: comparisons across nonrandomized cohorts can be affected by differences in participant characteristics, follow-up, or other factors. The registry record does not report a model or adjustment that would address such factors, so cohort contrasts should not be treated as causal or as comparative treatment effects.

How should uncertainty be understood?

General statistical explanation: observed counts are estimates of what was seen in the study, not guarantees of what would be seen in another population or study. A confidence interval, when reported, expresses statistical uncertainty around an estimate under a specified method and assumptions. The registry record does not report confidence intervals or other uncertainty intervals for these safety counts. It also does not report a comparative effect estimate or an inferential test for the primary endpoint. The precision of the posted counts therefore cannot be assessed from a registry-reported interval.

The registry lists pharmacokinetic outcomes in Part 1 for MMF and HES, including plasma concentrations, maximum observed concentration, and area under the concentration-time curve. These outcomes concern drug-metabolite exposure rather than the primary participant-count endpoint. The record does not report pharmacokinetic result values in the material describing the primary safety outcome, so no numerical exposure interpretation can be made from these safety counts.

What do planning calculations mean?

General statistical explanation: sample-size calculations estimate the number of participants or events needed to target a specified statistical precision or power under stated assumptions. They are planning illustrations, not observed results or evidence that a study had a particular probability of detecting an effect. The registry's stated planning assumptions describe a two-arm, equal-allocation calculation based on a fraction of an observed effect, while this study is single-arm and has no like-for-like control comparison. Such a calculation should not be mistaken for a design feature of this trial or for evidence of observed power.

The registry record does not report the protocol's sample-size justification, any interim analyses, or a statistical analysis plan for the primary safety outcome. In the absence of those details, interpretation should remain tied to the descriptive endpoint, its stated population, and its stated follow-up period.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was handled across the primary and secondary outcomes. The listed objectives cover safety and tolerability in Part 1 and Part 2, along with several pharmacokinetic outcomes for MMF and HES in Part 1. When a study examines multiple outcomes, general statistical practice may address the increased chance of observing a seemingly notable result by specifying a testing hierarchy or adjustment. No such approach is reported in the registry record, so no claim about adjusted or unadjusted statistical significance can be made.

Missing-data handling for the primary endpoint is not reported in the registry record. The stated safety analysis set includes participants who received at least 1 dose of study treatment, and adverse events for participants who prematurely discontinued were reported up to 2 weeks post discontinuation. The record does not explain how incomplete follow-up, missing event details, or differences in exposure duration were handled in analyses. It also does not report imputation or sensitivity analyses for missing safety information.

The registry identifies a subset for the pharmacokinetic objective, but the selection rules and missing-data methods for that subset are not reported in the registry record. The recorded primary endpoint is descriptive, and no inferential analysis or adjustment for multiplicity is reported. These omissions limit interpretation of statistical uncertainty and of results across the set of outcomes.

11. 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: multiple sclerosis relapse (6.0%), iron deficiency anaemia (2.0%), demyelination (2.0%), relapsing-remitting multiple sclerosis (2.0%), staphylococcal bacteraemia (1.9%).

For serious adverse events, the registry lists 6 of 52 participants in Cohort 1: Japanese Participants and 6 of 50 participants in Cohort 2: Chinese Participants. Deaths are listed as 0 in each cohort. These counts are participant counts, not counts of all individual event occurrences; the registry outcome is framed as the number of participants with events.

Serious adverse events are defined by outcomes such as death, a life-threatening event, inpatient hospitalization or its prolongation, significant disability or incapacity, congenital anomaly, or medical importance. This definition does not establish that an event was caused by DRF. TEAEs include both serious and non-serious events, and the posted counts for other adverse events are 50 of 52 in the Japanese cohort and 42 of 50 in the Chinese cohort.

The registry lists several serious-event terms with percentages, but their population basis is not reported in the registry record. Those percentages cannot be assigned to a particular cohort from the record. The cohort counts and listed terms are descriptive safety information, not a controlled comparison.

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

The results describe safety events recorded among participants treated with DRF in an open-label, single-arm study. The registry reports serious adverse events for 6 of 52 Japanese participants and 6 of 50 Chinese participants, with no deaths listed in either cohort. Other adverse events are listed for 50 of 52 Japanese participants and 42 of 50 Chinese participants. These counts are tied to the registry's safety analysis set and the recorded endpoint definitions.

The findings do not show whether event frequencies are higher or lower than they would have been without DRF or with another treatment. There is no comparator group, and the events include those whether or not related to the study product. The record therefore does not establish causation or a comparative safety effect. Nor do participant counts alone describe event duration, recurrence, or all aspects of severity.

The primary outcome covers Part 1 through Week 24, while the study objectives also include safety and tolerability through Week 48 in Part 2. The reported primary endpoint counts should not be extended to imply complete follow-up through Week 48. The record specifies additional adverse-event reporting after premature discontinuation, but does not report details of missing follow-up or an analysis of exposure time.

The registry record does not report confidence intervals, statistical tests, or comparative effect estimates for the primary safety endpoint. As a result, the posted counts give a descriptive account but do not quantify statistical uncertainty through an interval or test. They also do not establish the expected frequency of events in other populations or settings. The scope of interpretation is limited to the cohorts, endpoint definitions, and follow-up described in the record.

13. Why This Trial Matters Statistically

This study illustrates an important distinction in clinical biostatistics: describing events in a treated cohort is not the same as estimating a comparative treatment effect. Counts of participants with TEAEs and TESAEs can characterize what was recorded during the stated follow-up. Without a comparator, however, the results cannot separate treatment-associated effects from other reasons events may occur.

The record also makes the definition of the safety endpoint central to interpretation. TEAEs are determined by timing relative to treatment, whereas serious events are classified by consequences or medical importance. These concepts answer different questions. Neither the timing designation nor the serious classification alone establishes that DRF caused an event.

Finally, the safety population, observation period, and handling of premature discontinuation shape what the counts mean. The registry identifies a safety analysis set and states an adverse-event reporting window, but it does not report uncertainty intervals, a comparative analysis, or methods for missing data. Reading the counts alongside those design and reporting limits helps prevent descriptive safety findings from being treated as causal or more precise than the record supports.

14. 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 principal limitation for comparative interpretation is the single-arm design: no control group is listed, and the study is open-label with no masking. The Japanese and Chinese cohorts are descriptive cohorts, not randomized comparator groups. Differences between their counts cannot be assigned to treatment or to a specific participant characteristic on the basis of the registry record.

The primary endpoint is a participant count. The registry record does not report confidence intervals, inferential tests, adjusted estimates, or event rates over time for this endpoint. It does not report the protocol's sample-size justification, interim analyses, or a statistical analysis plan. Methods for missing data and incomplete follow-up are also not reported, although the record specifies post-discontinuation adverse-event reporting for prematurely discontinued participants.

The registry's listed serious-event term percentages do not have a reported population basis in the record. The result description therefore does not support assigning those values to a cohort or deriving additional event counts. The record also describes objectives through Week 48, while the primary outcome timeframe is through Week 24; these periods should not be conflated.

The study title refers to the Asia-Pacific region, while its objective description and cohorts identify East Asian, Japanese, and Chinese participants. The registry record does not describe additional participant groups in the outcome counts. The findings should therefore be interpreted in relation to the populations expressly identified in the record, rather than generalized beyond them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Diroximel Fumarate (DRF) in Adult Participants From the Asia-Pacific Region With Relapsing Forms of Multiple Sclerosis (RMS) — NCT05083923.
• Registry record last updated 2025-10-24; status last verified 2025-10.
• Results first posted 2025-10-24.
• 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.

18. Record Summary

The registry identifies NCT05083923 as a completed Phase 3, open-label, single-arm, multicenter study of DRF in adults with RMS. It lists enrollment of 136, a start date of 2021-11-18, and a primary completion date of 2024-09-11.

The primary outcome is the number of participants with TEAEs and TESAEs in Part 1, from Baseline (Day 1) up to Week 24. The safety analysis set includes participants who received at least 1 dose. Serious adverse events are listed for 6 of 52 Japanese participants and 6 of 50 Chinese participants; deaths are listed as 0 in each cohort.

The record describes DRF dosing through Week 48 and includes Part 2 safety objectives and Part 1 pharmacokinetic objectives. It reports no comparator group and does not report comparative estimates, confidence intervals, statistical tests, or missing-data methods for the primary endpoint.