Effect of MD1003 in Progressive Multiple Sclerosis (SPI2): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of MD1003 in Progressive Multiple Sclerosis (SPI2) (NCT02936037), a randomized phase 3 study. The primary outcome is Proportion of Patients Improved on Either Expanded Disability Status Scale (EDSS) or Time to Walk 25 Feet (TW25).

2. Clinical Question

3. Trial Design

SPI2 is described as a phase 3, randomized, parallel-group study comparing MD1003 with placebo in progressive multiple sclerosis. The official title identifies it as double blind and placebo controlled; the registry’s masking classification is quadruple. The roles covered by that classification are not reported in the registry record.

The recorded enrollment is 642. The registry lists 316 participants for the placebo arm and 326 for the MD1003 arm. These are the arm sizes recorded alongside the primary outcome; the analysis populations for each outcome are not reported. The sponsor is MedDay Pharmaceuticals SA. The study started in 2016-12, had a primary completion date of 2019-11-15 and is listed as terminated. The reason for termination is not reported in the registry record.

Both arms used capsules on the same schedule: one capsule in the morning, at noon and in the evening. The arm descriptions state a treatment period of 15 months and up to 27 months. The primary endpoint’s timeframe is 15 months, with improvement assessed using measurements at Month 12 and Month 15. The registry also lists secondary outcomes concerning 12-weeks confirmed EDSS progression, patient- and physician-evaluated improvement, and mean change in TW25 between M0 and M15.

Random allocation and a parallel-group structure support a comparison between assigned groups, but details of sequence generation, allocation concealment, adherence, treatment discontinuation and follow-up procedures are not reported in the registry record. The record does not state the protocol’s statistical plan or explain why the study was terminated.

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.

Double-Blind Treatment Period

Reasons for not completing this period:

Open Label Extension

Reasons for not completing this period:

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 Proportion of Patients Improved on Either Expanded Disability Status Scale (EDSS) or Time to Walk 25 Feet (TW25), measured over 15 months.

The primary endpoint is the proportion of patients who improved on either EDSS or TW25 by the 15-month assessment. EDSS is a disability scale; TW25 measures the time needed to walk 25 feet. Using either measure can capture improvement expressed through disability status or walking performance, rather than requiring improvement on both. This is a composite, “either/or” definition, so meeting either qualifying condition counts as improvement.

For EDSS, the registry defines improvement as a decrease of at least 1 point for an initial EDSS from 3.5 to 5.5, or at least 0.5 point for an initial EDSS from 6 to 6.5. The decrease had to be present at Month 12 and confirmed at Month 15. For TW25, improvement was at least 20% at Month 12 and Month 15 compared with the baseline value. The baseline TW25 was the lowest of four values from the inclusion and randomization visits; the baseline EDSS and TW25 values were selected as the lowest among the inclusion and randomization visits.

These rules aim to identify improvement that persists to the later assessment rather than a change at only one visit. The registry reports 9.2% for placebo and 12.0% for MD1003. It does not provide confidence limits or an estimable two-arm comparison for the primary endpoint, so the precision and statistical evidence for the contrast cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry presents a primary endpoint as a percentage, but identifies the outcome type as count other and marks a two-arm comparison as not estimable. The result should therefore be read as two reported arm-level proportions, not as a complete inferential comparison. No new contrast, uncertainty interval or significance test can be recovered from the posted record without making assumptions or calculations beyond what it reports.

What does a proportion describe?

General: A proportion expresses how many members of a defined group meet an outcome criterion relative to the group being analyzed. Its interpretation depends on a clear numerator, denominator, outcome definition and analysis population. Here the endpoint definition is described, and the registry reports 9.2% for placebo and 12.0% for MD1003. The record does not give the corresponding event counts or specify the analysis population for these percentages.

A percentage is descriptive. Comparative inference ordinarily also communicates uncertainty, often through a confidence interval and a test or model-based estimate. A confidence interval describes the range of values reasonably compatible with the data under the method’s assumptions; it is not a guarantee that the true effect lies within that range. No confidence interval or p-value is reported for this primary comparison.

Why is the endpoint a composite?

General: A composite endpoint combines multiple event or measurement criteria into one outcome. An “either/or” rule can count a participant as meeting the endpoint through any qualifying component. This can represent more than one clinically relevant way of changing, but the combined result does not show how often each component contributed unless component-specific results are reported.

In SPI2, qualifying improvement could be based on EDSS or TW25. The registry specifies different criteria for the two components: an EDSS decrease appropriate to the initial EDSS range, confirmed between Month 12 and Month 15, or a TW25 improvement of at least 20% at both assessments. The record does not report component-specific counts, so the relative contribution of EDSS and TW25 to the overall percentages is not available.

What can randomization contribute?

General: Random assignment is intended to make treatment groups comparable, on average, with respect to factors measured and unmeasured at baseline. This supports a causal comparison when the trial is conducted and analyzed as planned, but randomization does not itself supply an effect estimate or resolve missing-outcome concerns. The registry identifies the study as randomized, but sequence generation, allocation concealment, adherence and the analysis population are not reported.

The parallel design means the registry describes separate groups assigned to MD1003 or placebo. The matching capsule schedule is recorded for both arms. The official title calls the study double blind, while registry masking is classified as quadruple; the specific people masked are not described in the record.

What does “not estimable” mean in this record?

General: An estimate is not estimable when the available information or the selected analysis does not support calculating the requested comparison. This does not mean that the groups are identical, nor does it establish that a difference exists. The registry’s notation indicates that a two-arm comparison for this count-other endpoint is not available in the posted results. The arm percentages remain reportable descriptions, but they do not substitute for an interval estimate or a test.

Sample-size calculations are planning illustrations, not observed power. General planning calculations depend on assumptions about the target effect, allocation and statistical method. The registry record does not report the trial’s own sample-size justification or statistical plan, and the planning assumptions described for any illustration should not be mistaken for the protocol’s design rationale.

What additional methods would clarify the result?

General: A complete statistical account would identify the analysis population, explain how missing assessments and withdrawals were handled, state the planned comparison and adjustment strategy, and report an effect estimate with its uncertainty. For a composite outcome, component-specific results can help readers understand what generated the overall endpoint. These are standard interpretive considerations; their use in SPI2 is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures and identifies 3 secondary outcomes: time to 12-weeks confirmed EDSS progression, CGI-I improvement assessed by the patient and evaluating physician, and mean change in TW25 between M0 and M15. Numerical findings for those secondary outcomes are not reported in the registry record. The number of posted analyses is 0.

Multiplicity arises when a study tests or estimates several outcomes, time points, groups or analyses. General: With multiple statistical tests, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the testing structure. A statistical plan may designate a primary outcome, specify testing order or adjust inference, but the trial’s planned multiplicity strategy is not reported in the registry record. The endpoint listing alone cannot establish how multiplicity was handled.

The record does not describe missing-data methods, the number of participants with observed primary endpoint data, or the analysis population. It also does not say whether analyses followed assignment regardless of treatment received, or whether another population was used. The reported arm sizes are listed alongside the primary result, but should not be assumed to be the denominator for every outcome.

General: Missing outcome data can affect estimates when the likelihood of missingness is related to prognosis or treatment, and different assumptions can lead to different conclusions. The registry’s silence does not establish that data were missing or that a particular method was used. The primary percentages should therefore be interpreted without assuming a missing-data procedure or a specific analysis population.

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 (10.0%), multiple sclerosis (1.9%), urinary tract infection (1.9%), trigeminal neuralgia (1.3%), muscular weakness (1.2%).

The registry reports serious adverse events for GROUP 1, the placebo arm, and GROUP 2, the MD1003 arm. For serious adverse events, 82 participants were affected among 311 at risk in GROUP 1, and 87 were affected among 331 at risk in GROUP 2. The record reports 0 deaths in GROUP 1 and 1 in GROUP 2. These are descriptive safety counts; the registry does not report a comparative statistical analysis for them.

For other adverse events, the registry lists 264 affected among 311 at risk in GROUP 1 and 277 among 331 at risk in GROUP 2. “At risk” is the registry’s denominator label. The record does not provide event-specific exposure time or details about severity, duration, recurrence, attribution or handling of participants with multiple events. The counts therefore should not be interpreted as rates adjusted for time on treatment, nor as evidence that an event was caused by the assigned capsule.

The most commonly listed serious adverse-event terms include multiple sclerosis relapse (10.0%), multiple sclerosis (1.9%), urinary tract infection (1.9%), trigeminal neuralgia (1.3%), muscular weakness (1.2%) and urosepsis (1.0%). The registry does not clarify in this summary how these terms map to treatment arms or whether the percentages use a common denominator. They are best read as listed terms, not as a comparison between arms.

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

The primary results show the registry-reported proportions meeting the composite improvement definition: 9.2% in the placebo arm and 12.0% in the MD1003 arm. They do not include the uncertainty estimate or inferential comparison needed to judge the precision of a between-arm effect. The record explicitly marks the two-arm comparison as not estimable for this count-other endpoint.

The endpoint allows improvement through either EDSS or TW25. It therefore summarizes two different forms of measured change under specified criteria and confirmation visits. Without component-specific findings, the overall percentage does not show which measure contributed to the result. Nor does the registry provide enough information to determine whether the reported percentages use all randomized participants or another analysis population.

These results do not, by themselves, establish the size or statistical certainty of a treatment effect. They also do not establish that there was no effect. A missing comparative estimate is not evidence of equivalence; equivalence would require an appropriate design and analysis, neither of which is described for this purpose in the registry record. The record does not report a confidence interval, p-value or adjusted analysis for the primary endpoint.

The study is marked terminated, but the reason and its relationship to the analysis are not reported. The registry does not provide the statistical plan, sample-size justification, missing-data approach or numerical findings for the listed secondary outcomes. Those omissions limit evaluation of how the primary finding fits into the full planned analysis.

Safety counts are also descriptive. They report affected participants and deaths by group, but do not give comparative estimates or enough detail to assess event timing, exposure-adjusted rates or attribution. They should be considered separately from the primary endpoint and should not be read as proof of cause.

13. Why This Trial Matters Statistically

SPI2 is statistically notable for combining two different clinical measurements in a single primary endpoint. EDSS and TW25 capture distinct aspects of disability and walking performance, and the registry’s “either/or” rule makes improvement on either sufficient. That approach can make an endpoint responsive to more than one type of change, but it also means an overall percentage can conceal whether one component chiefly accounts for the result. Component-level results would help interpret that composite; they are not reported in the registry record.

The endpoint also requires confirmation across Month 12 and Month 15, rather than counting a qualifying change at only one assessment. This makes the definition more specific than a single-visit measurement. However, interpreting such a rule depends on complete follow-up and transparent handling of missing assessments, neither of which is described in the registry record.

The reported primary proportions are available, but the two-arm comparison is marked not estimable and no confidence interval or p-value is posted. This distinction is important: descriptive data and comparative statistical evidence are not interchangeable. A statistical reader needs to know both the observed outcome summaries and the uncertainty around the contrast to evaluate its precision.

Finally, the record identifies multiple outcome measures and lists secondary endpoints, but does not report a statistical plan or numerical results for those secondary outcomes. Without that context, readers cannot determine the planned hierarchy of analyses or how multiple outcomes were intended to be interpreted. The trial thus illustrates why endpoint definitions, analysis details and uncertainty estimates are essential alongside arm-level percentages.

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.

Several trial-specific reporting gaps constrain interpretation. The registry does not report the primary-outcome population, component-specific EDSS and TW25 results, event counts corresponding to the reported percentages, confidence intervals or a p-value. It marks the two-arm comparison as not estimable. As a result, the primary outcome can be described by arm, but the magnitude and precision of the comparative effect cannot be evaluated from the record.

The record lists 9 outcome measures but gives only 3 secondary outcome titles, with no numerical findings for those outcomes. It does not report a statistical analysis plan, multiplicity strategy, sample-size justification, missing-data method or analysis population. These gaps prevent assessment of whether the posted primary result corresponds to the planned analysis and how incomplete assessments, if any, were handled.

The registry classifies masking as quadruple, while the official title describes the study as double blind. The roles covered by the masking classification are not reported. The record also does not describe allocation concealment, adherence, treatment exposure, or the reason for the terminated status. The termination status alone cannot establish early stopping or explain the availability of results.

Safety reporting includes affected participants and deaths, but does not provide comparative statistical analysis, exposure-adjusted rates, event timing or attribution. The listed serious-event terms are not accompanied by enough information in the summary to interpret their arm-specific distribution. These limitations are specific to the information in the registry record and do not establish that relevant methods or analyses were absent from other trial documents.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of MD1003 in Progressive Multiple Sclerosis (SPI2) — NCT02936037.
• Registry record last updated 2020-11-23; status last verified 2020-10.
• Results first posted 2020-11-23.
• 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

NCT02936037, titled “Effect of MD1003 in Progressive Multiple Sclerosis (SPI2),” is a phase 3 randomized parallel-group study sponsored by MedDay Pharmaceuticals SA. Its official title describes a double-blind, placebo-controlled study; registry masking is classified as quadruple. The study started in 2016-12, had a primary completion date of 2019-11-15 and is listed as terminated.

The primary endpoint is the proportion improved on EDSS or TW25 at the 15-month timeframe. The registry reports 9.2% for placebo and 12.0% for MD1003, but marks the two-arm comparison as not estimable. No confidence interval, p-value, analysis population or numerical secondary-outcome results are reported in the registry record. Serious adverse-event counts and deaths are listed by group, without a comparative analysis.