Open Label Extension of Prior TERMS Study to Treat Relapsing Forms of Multiple Sclerosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open Label Extension of Prior TERMS Study to Treat Relapsing Forms of Multiple Sclerosis (NCT00595920), a na phase 2 study. The primary outcome is Evaluate Changes in Number of Combined Unique Active Lesions on Brain Magnetic Resonance Imaging (MRI).

2. Clinical Question

3. Trial Design

This was a Phase 2, single-group, open-label extension study of Tovaxin. The registry describes it as an extension for subjects previously treated in the TERMS study. No random allocation or masking is recorded, and the allocation field is marked NA. The study is listed as terminated. Its recorded start is 2007-11 and its primary completion is 2008-12.

The registry enrollment is 116, but the primary-outcome description reports that 38 patients were dosed. These figures refer to different aspects of the record and should not be treated as interchangeable. The description says the study was discontinued because of company financial constraints. Of the 38 patients dosed, 32 did not complete all 5 doses. Of the 6 who completed the 5 doses, 5 did not have a Wk 52 MRI. The record therefore says no efficacy results were summarized because there was no comparison data.

The intervention is described as Tovaxin, 30-45 million autologous myelin reactive T cells. The registry lists three outcome measures, including the primary MRI outcome and secondary outcomes concerning MS progression and annualized relapse rate. It lists no analyses. Details such as a planned statistical analysis, target sample-size justification, analysis populations, and the planned handling of missing outcomes are not reported in the registry record.

With a single open-label group, there is no concurrent control group for separating changes during the study from changes that might have occurred over time for other reasons. The extension can describe treatment exposure and recorded safety information, but the registry does not provide an analyzed efficacy comparison. The registry record does not report further protocol details that would clarify how outcome visits, treatment adherence, or MRI assessment were scheduled beyond the annual timeframe attached to the primary outcome.

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: This extension study was discontinued due to financial constraints. No efficacy results are summarized due to the small number of patients who received full treatment and follow-up.

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: Randomized and received at least one dose.

6. Primary Endpoint

The registry lists the primary outcome as Evaluate Changes in Number of Combined Unique Active Lesions on Brain Magnetic Resonance Imaging (MRI), measured over Annually.

The primary endpoint is described as changes in the number of combined unique active lesions on brain magnetic resonance imaging (MRI), with an annual timeframe. MRI lesion activity is an imaging measure intended to capture disease activity in the brain. Combining lesion categories into a single measure can provide a way to track several forms of active lesions together, rather than treating each type as a separate endpoint. That is a general rationale for a combined imaging endpoint; the registry does not define which lesion types were combined or specify the operational criteria used in this study.

To estimate change, observations at relevant time points must be available and comparable. The registry description says that of the 6 patients who completed the 5 doses, 5 did not have a Wk 52 MRI, and that no efficacy results were summarized because there was no comparison data. It does not report a unit, summary parameter, dispersion measure, or detailed MRI measurement procedure for the primary outcome. The exact timing and method for comparing scans are also not reported in the registry record.

Thus, the endpoint expresses the study’s intended efficacy question, not an observed treatment effect. Without the needed follow-up comparison, the number of lesions cannot be interpreted as having increased, decreased, or remained stable during the extension based on this registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on the design, the outcomes actually observed, and the analysis used. In this study, the registry records a single group, no masking, no allocation, and no summarized efficacy analysis. Those features sharply limit what statistical conclusions can be drawn. General statistical concepts can explain the limits, but they cannot fill in unreported trial results.

What does a single-group design estimate?

In general, a single-group study can describe outcomes among participants who receive an intervention. If it measures an outcome at baseline and again later, it may also describe within-person or group-level change, provided both measurements are available and the comparison is defined. A concurrent control group adds a reference for changes that would have occurred without the intervention. Without such a group, time trends, changes in other care, measurement variability, and other influences cannot be separated from the intervention effect just by observing change.

Here, the registry identifies no comparator and says that no efficacy results were summarized because comparison data were unavailable. As a result, there is no reported change estimate for the primary MRI outcome to interpret, even as a descriptive before-and-after result. The listed design does not support a controlled treatment contrast.

Why does missing follow-up matter?

For an outcome measured at follow-up, missing observations reduce the information available for estimating change. Missingness can also affect interpretation if the people with observed follow-up differ from those without it. That possibility is a general concern, not a finding about why MRI scans were missing in this study. The registry says that 5 of the 6 patients who completed the 5 doses did not have a Wk 52 MRI. It does not report why those scans were absent, whether any other MRI observations were available, or how missing outcome data were handled.

Common approaches to missing data rely on assumptions about why measurements are absent and how observed information relates to unobserved outcomes. Such assumptions should be stated and examined; they cannot be inferred from a count of missing scans. The registry record does not report an imputation method, a sensitivity analysis, or another missing-data procedure. Given the absence of a summarized efficacy comparison, no missing-data adjustment can be assessed from this record.

What would an estimate and its uncertainty mean?

In general, an estimate is a numerical summary of an outcome or contrast in a defined population. A confidence interval describes the range of values reasonably compatible with the estimate and the statistical model, and helps communicate precision. A p-value evaluates how compatible data are with a specified null hypothesis under a model; it is not the probability that a treatment works or that the null hypothesis is true. These concepts require data and an analysis that are not reported for the primary endpoint. No efficacy estimate, confidence interval, or p-value is summarized in the registry record.

Different outcome types can call for different models. A count outcome, for example, may have a distribution with variability greater than a basic count model allows. In general, over-dispersion means the observed variability exceeds the model’s expected variability; if ignored, uncertainty estimates and tests may be unreliable. This is a general methodological point, not a claim about the distribution of this study’s MRI outcome. The registry does not report the endpoint’s unit, dispersion, statistical model, or model diagnostics, so no model choice can be evaluated.

How should planning calculations be read?

Sample-size planning asks how much information a future design might need to detect a specified effect under stated assumptions. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target is described as a stated fraction of the observed effect. Such a calculation is conditional on its assumptions and is not a report of the extension’s own design. In particular, it does not change the fact that this extension is recorded as single-group, with allocation marked NA.

Planning calculations are not observed power. Observed power is not a substitute for reporting the estimated effect and its uncertainty. A planning illustration based on an effect also cannot establish that the effect was reliably observed in a study whose registry record summarizes no efficacy results. Any planning figures should therefore be understood as hypothetical design illustrations, not as evidence about treatment efficacy or a property of the completed extension.

What analyses are reported?

The registry lists three outcome measures and zero analyses. It does not report a statistical analysis plan, prespecified model, covariate adjustment, interim analysis, or multiplicity procedure. Those details should not be assumed. The absence of a reported analysis means there is no registry-based efficacy test to interpret, rather than a test that found no difference. A non-significant result would require a reported analysis; no such result is given.

In general, an analysis population defines which participants contribute to a particular estimate, such as all enrolled participants, those who received treatment, or those with outcome measurements. Different choices answer different questions and can produce different estimates. The registry does not report a named analysis population for efficacy. It is therefore important not to treat the enrollment figure, the dosed group, the dose completers, and those with MRI follow-up as if they were one interchangeable analysis set.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures: the primary MRI outcome, changes in MS progression, and annualized relapse rate. It does not report an analysis for any of them; the record lists zero analyses. A multiplicity plan specifying how to interpret several outcomes or tests is not reported in the registry record. In general, when multiple hypotheses are tested, the chance of at least one apparently positive result can increase unless the analysis plan accounts for the testing strategy. That general issue does not imply that any particular test was performed.

Missing follow-up is especially relevant to the primary MRI outcome. The description says that 5 of the 6 patients who completed the 5 doses did not have a Wk 52 MRI, and that no efficacy results were summarized because there was no comparison data. The record does not report reasons for the missing scans, whether other follow-up scans were available, or a procedure for handling missing data. It also does not report sensitivity analyses that would show how conclusions might change under different assumptions about those missing observations.

The analysis population for efficacy is not reported in the registry record. The recorded enrollment of 116, the 38 patients dosed, those who completed all 5 doses, and those with follow-up MRI should not be conflated. The record does not specify whether an intention-to-treat, treated-participant, completer, or other population was planned for analysis. Because no efficacy estimate is summarized, there is no basis for evaluating how the choice of analysis population or missing-data assumptions affected an estimate.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 (2.6%).

The registry reports one serious-adverse-event affected count in the Open Label Extension group, with 38 at risk. For other adverse events, it reports an affected count of 25, also with 38 at risk. These are separate registry categories and should be read as recorded counts, not as efficacy outcomes. The registry also lists Multiple Sclerosis Relapse at 2.6% among the top serious terms.

The serious-adverse-event affected count does not by itself describe the event’s severity beyond its registry classification, its timing, its duration, or whether it was judged related to Tovaxin. Those details are not reported in the registry record. The listed term should not be interpreted as establishing causation. The deaths field is null, so the registry does not report a death count in the record.

Safety counts from a single-group extension do not provide a controlled comparison of event risk. Without a concurrent comparator and fuller event details, these figures describe what the registry records for the extension group but cannot establish how event rates compare with another treatment or with no treatment. They also do not resolve whether all participants had the same duration of observation.

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

The registry record establishes the study’s purpose and intended primary outcome: to further evaluate Tovaxin in relapsing forms of multiple sclerosis, with changes in combined unique active brain MRI lesions as the primary measure. It also records that the extension was discontinued because of company financial constraints, that 38 patients were dosed, and that many did not complete the planned treatment and MRI follow-up described in the outcome text.

It does not establish whether Tovaxin reduced, increased, or had no effect on MRI lesion activity. No efficacy results are summarized, and the record explains that comparison data were not available. A lack of summarized results is not the same as a finding of no effect. Nor does it mean that a statistical test found no difference: no efficacy analysis is listed.

The study’s single-group, open-label design also limits causal interpretation. In general, without a concurrent comparison group, observed changes cannot be attributed to treatment alone. Even if an outcome estimate had been reported, the design would not provide the same kind of controlled comparison as a randomized trial. In this registry record, the missing follow-up comparison means that even a within-group efficacy change is not available for interpretation.

The safety entries provide limited descriptive information: the registry records serious-adverse-event and other-adverse-event affected counts for the extension group and lists a serious term. They do not, on their own, prove that Tovaxin caused an event or establish a comparative safety profile. Further event descriptions and comparative data are not reported in the registry record.

Any sample-size planning illustrations are hypothetical calculations under stated assumptions, not observed power and not evidence that an effect was detected. The record therefore supports a cautious account of study design, exposure, incomplete follow-up, and the presence of recorded adverse-event counts. It does not support a conclusion about efficacy or a precise estimate of treatment benefit or harm.

13. Why This Trial Matters Statistically

This study illustrates why registry enrollment, treatment exposure, and outcome follow-up are distinct parts of a trial record. Enrollment is recorded as 116, while the primary-outcome description says that 38 patients were dosed. Among those dosed, 32 did not complete all 5 doses; among the 6 who completed the doses, 5 did not have a Wk 52 MRI. Each figure describes a different point in study participation and does not, by itself, define an efficacy analysis population.

It also shows that an endpoint can be clearly named while still lacking the observations needed for a meaningful estimate. The primary question concerned annual changes in combined unique active MRI lesions, but the registry says no efficacy results were summarized because there was no comparison data. A stated endpoint is not the same as a reported outcome estimate, and a plan to measure an outcome cannot replace observed follow-up.

The design matters as well. In a single-group open-label extension, there is no concurrent control group for estimating how outcomes might have changed in the absence of the intervention. In general, a controlled comparison can help distinguish treatment-associated differences from background change and other influences. Here, the registry’s missing efficacy summary adds a further limit: it does not offer even a numerical within-group MRI change.

Finally, the record distinguishes safety reporting from efficacy analysis. It contains adverse-event counts but lists no analyses and no efficacy results. Reading these entries separately avoids treating safety counts as evidence about the MRI endpoint, or treating missing efficacy results as a negative efficacy finding. The trial is statistically informative as an example of how incomplete exposure and follow-up, coupled with a single-group design, constrain interpretation.

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 limitations specific to this extension constrain interpretation. The primary outcome description states that the study was discontinued because of financial constraints and that no efficacy results were summarized. It reports that 32 of the 38 patients dosed did not complete all 5 doses. Among the 6 who did complete the doses, 5 did not have a Wk 52 MRI. The record therefore lacks the comparison data needed for the planned primary efficacy summary.

The design was single-group and open-label, with allocation marked NA and masking marked none. A concurrent comparator is not listed. This means the record does not support a controlled estimate of treatment effect. Even if outcome changes had been available, a single-group comparison would be limited for separating intervention effects from changes over time or other influences.

The registry enrollment of 116 differs from the 38 patients reported as dosed in the primary-outcome description. The record does not explain this difference or report further details on participant flow. It also does not provide the reasons individual patients did not complete doses or obtain the Wk 52 MRI. These omissions prevent a fuller assessment of follow-up and of how the observed participants might differ from those without complete treatment or imaging.

Further protocol and analysis details are not reported in the registry record. These include the primary outcome’s unit and measurement definition, an efficacy analysis population, a statistical model, a missing-data method, a multiplicity plan, and a sample-size justification for the extension. The registry also lists no analyses. Consequently, there is no reported estimate or uncertainty measure for the primary outcome, and no basis for evaluating statistical significance, precision, or robustness.

The safety information is also limited to registry counts and a listed serious-event term. Event-level details, attribution, and comparative safety data are not reported in the registry record. Taken together, the available information supports describing study conduct and the reported safety summaries, but not estimating efficacy or making a controlled safety comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open Label Extension of Prior TERMS Study to Treat Relapsing Forms of Multiple Sclerosis — NCT00595920.
• Registry record last updated 2016-03-15; status last verified 2014-02.
• Results first posted 2016-03-15.
• 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.

18. Record Summary

NCT00595920 is a Phase 2, single-group, open-label extension of prior TERMS study treatment, evaluating Tovaxin in relapsing forms of multiple sclerosis. The registry records enrollment of 116, a start date of 2007-11, primary completion of 2008-12, and a terminated status. The primary outcome was changes in the number of combined unique active lesions on brain MRI, with an annual timeframe.

The primary-outcome description reports 38 patients dosed, 32 who did not complete all 5 doses, and 6 who completed them. Of those 6, 5 did not have a Wk 52 MRI. The extension was discontinued because of company financial constraints, and no efficacy results were summarized because comparison data were unavailable. The registry lists three outcome measures and zero analyses.

Safety entries record serious-adverse-event and other-adverse-event affected counts of 1 and 25, respectively, among 38 at risk; Multiple Sclerosis Relapse is listed at 2.6% among top serious terms. The record does not provide a controlled efficacy estimate.