Study of the Effect of BG00012 on MRI Lesions and Pharmacokinetics in Pediatric Subjects With RRMS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of the Effect of BG00012 on MRI Lesions and Pharmacokinetics in Pediatric Subjects With RRMS (NCT02410200), a na phase 2 study. The primary outcome is Change in the Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans From the Baseline Period to On-Treatment Assessment Period.

2. Clinical Question

3. Trial Design

This was a Phase 2, open-label, multicenter, multiple-dose study of BG00012 in pediatric participants with RRMS aged 10 to 17 years. The record describes a single-group model, with allocation listed as not applicable and no masking. It therefore does not describe a randomized comparison between treatment groups. The registry lists enrollment as 22 and the study status as completed.

Participants received oral BG00012, or dimethyl fumarate, at 120 mg twice daily for the first 7 days, followed by 240 mg twice daily for 24 weeks. The primary objective concerned the effect on brain MRI lesions. Secondary objectives concerned pharmacokinetics, safety, and tolerability. Listed pharmacokinetic measures include maximum observed plasma concentration, time to maximum observed plasma concentration, apparent clearance, apparent volume of distribution, half-life, and area under the concentration-time curve from time 0 to infinity. The safety outcomes include participants experiencing treatment-emergent adverse events and serious adverse events.

The primary endpoint compares lesion counts across two defined assessment periods: a baseline period from Week -8 to Day 0 and an on-treatment assessment period from Week 16 to Week 24. Those periods describe when measurements were taken, not separate study arms. The primary analysis population is restricted to participants with new or newly enlarging T2 lesions during baseline and a post-baseline assessment; its size is not reported in the registry record.

The study start date is 2015-09-30, and the primary completion date is 2016-09-23. The registry does not report a comparator group or a randomized treatment assignment. That design limits what can be concluded about differences relative to another treatment or to a concurrent control condition.

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: Primary Analysis Population: participants having new or newly enlarging T2 lesions during the Baseline period with a post-baseline assessment.

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 Change in the Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans From the Baseline Period to On-Treatment Assessment Period, measured over Baseline Period (Week -8 to Day 0), On-Treatment Assessment Period (Week 16 to Week 24).

The primary endpoint is the change in the number of new or newly enlarging T2 hyperintense lesions on brain MRI, comparing the baseline period with the on-treatment assessment period. The baseline period is Week -8 to Day 0; the on-treatment assessment period is Week 16 to Week 24. The registry describes the endpoint as a continuous measure summarized by a mean and standard deviation, with lesions as the unit.

The analysis population is defined as participants who had new or newly enlarging T2 lesions during baseline and a post-baseline assessment. This condition matters when interpreting an estimate: it defines which participants contribute to the primary analysis, rather than necessarily representing everyone enrolled. The number included in that analysis is not reported in the registry record.

In general, an MRI lesion endpoint offers a way to quantify imaging findings at specified time periods. Comparing the count across periods describes change in that imaging measure; it does not, on its own, describe every aspect of a participant’s health or experience. The registry identifies lesion change as the primary objective’s measure, but does not report the mean change, its variability, a confidence interval, or a hypothesis-test result. Consequently, the direction, size, and precision of the endpoint estimate cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. It does not report a numerical estimate, a confidence interval, a p-value, or the detailed statistical procedure used to obtain an estimate. The design is single-group and open-label. These registry entries shape what can be said about the analysis and what remains unknown.

What does a mean change describe?

In general, a mean summarizes the average value of a measurement across the observations included in an analysis. For a change endpoint, the estimate is intended to summarize the average difference between the measurements from the stated assessment periods, according to the analysis definition. Its interpretation depends on how the change is calculated and on which participants contribute. The registry defines the periods and an analysis population, but the detailed calculation rules are not reported in the registry record. The mean and standard deviation values are also not reported.

In general, a standard deviation describes how spread out individual measurements are around their mean. A large spread can make an average less representative of any one participant’s experience and can affect how precisely a population mean is estimated. The standard deviation is not itself a confidence interval and does not tell how certain the mean is without additional information about the analysis and the observations.

What would a confidence interval add?

In general, a confidence interval places an estimate in context by giving a range of values compatible with the observed data under the specified statistical method. A narrow interval indicates greater statistical precision than a wide interval, while both the estimate and its interval must be considered to understand the possible magnitude and direction of an effect. A confidence interval would not automatically resolve questions about bias, clinical relevance, or whether an observed change was caused by treatment. No interval for the primary endpoint is reported in the registry record.

How does the single-group design affect interpretation?

With one treatment group, the study can describe measurements before and during treatment, but it does not estimate a randomized contrast against a separate control group. In general, a baseline-to-follow-up change may reflect treatment as well as time-related changes, measurement variability, or other influences. A concurrent comparator can help distinguish such influences when it is appropriately assigned and analyzed. This record identifies no comparator and no random allocation, so no controlled treatment difference can be interpreted from it.

The open-label description means masking is listed as none. The registry does not explain whether outcome assessment was independently masked or describe procedures intended to limit measurement bias. Those details are not reported in the registry record and should not be inferred from the study label alone.

What do the planning illustrations mean?

General statistical interpretation: sample-size calculations are planning tools that estimate the number of participants needed under assumptions about an effect, variability, significance level, power, allocation, and analysis method. They are not a measure of how much power a completed study actually had. The registry’s planning assumptions describe 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. Those assumptions describe an illustration, not the stated design of this single-group study. The registry record does not report that these were the trial’s original design assumptions, and no sample-size justification is reported in the registry record. Any illustrative sample sizes should therefore be read as planning examples rather than observed power or as a reconstruction of the study’s protocol.

In general, a calculation based on a fraction of an observed effect is conditional on that effect estimate. If the estimate is uncertain, a planning calculation that uses it inherits that uncertainty. Such an illustration does not establish that the effect is reliable, clinically important, or likely to recur. It also does not change the fact that the study itself is described as single-group rather than as an equal-allocation two-arm trial.

Why do model assumptions matter?

In general, statistical methods rely on assumptions about the measurement scale, distribution, dependence between observations, and how missing observations are handled. For a lesion-count outcome, the detailed method matters because counts may be unevenly distributed or include many low values; the method used should match the data and study question. This is a general consideration, not a claim about the observed distribution in this study. The registry record does not report a distributional assessment, model specification, transformation, adjustment variables, or sensitivity analysis.

Over-dispersion is a general statistical concern when count data vary more than a chosen model expects. If present, it can make standard errors based on a simpler model too small, yielding intervals that appear more precise than warranted. Whether over-dispersion was present or addressed in this study is not reported in the registry record. The same caution applies to other modeling choices: without the analysis specification and endpoint results, the adequacy of a particular method cannot be assessed.

The record lists one analysis and eight outcome measures, but it does not describe the statistical plan governing those measures. A count of analyses or outcomes does not reveal whether tests were planned, which outcomes were confirmatory, or whether any adjustment was made for multiple testing. Those details are not reported in the registry record. Accordingly, no claim about statistical significance or multiplicity-adjusted evidence can be made from the information recorded.

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("BG00012")
n   <- c(15)
m   <- c(-7.9)
sp  <- c(16.23)
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  BG00012  15  -7.900  16.230  -16.888  1.088

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary MRI lesion endpoint and secondary pharmacokinetic and safety outcomes. It does not report the statistical plan for testing or estimating these outcomes, the hierarchy among secondary measures, or whether adjustment for multiple comparisons was planned. Multiplicity methods and their consequences for interpretation are therefore not reported in the registry record. The listing of several outcomes alone does not establish that each was tested, nor does it indicate how any tests were interpreted.

The primary analysis population is defined as participants with new or newly enlarging T2 lesions during the baseline period and a post-baseline assessment. The number of participants meeting that definition is not reported in the registry record. The record does not explain how the analysis handled participants without the required baseline lesion activity, without a post-baseline assessment, or with incomplete measurements. It also does not describe imputation, exclusion rules, or sensitivity analyses for missing data. These procedures are not reported in the registry record.

The record identifies the endpoint periods and says the outcome is summarized by a mean and standard deviation, but it does not report the estimator’s detailed specification, any covariate adjustment, or the primary endpoint result. Interim analyses and stopping rules are not reported in the registry record. A sample-size justification for the study is also not reported in the registry record. The separate planning assumptions describe an illustration, not a confirmed account of the study’s original statistical design.

These gaps limit assessment of how the analysis population was formed, how incomplete data may have affected the estimate, and how uncertainty was quantified. They do not establish that a particular method was or was not used; they mark details unavailable in the registry record.

12. 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 (18.2%), vertigo (4.5%).

The registry reports serious adverse events for the BG00012 group, with 22 participants at risk and 5 affected. For other treatment-emergent adverse events, it reports 22 at risk and 19 affected. These are separate categories in the safety summary. They should be read as counts of participants reported with events, not as a count of all individual event episodes. The record does not specify whether a participant could contribute to both categories.

The listed serious adverse-event terms are multiple sclerosis relapse, reported as 18.2%, and vertigo, reported as 4.5%. These are registry-reported percentages and are not recalculated. The term summaries do not, by themselves, describe event duration, recurrence, timing, relatedness to treatment, or outcome. Additional detail on those aspects is not reported in the registry record.

The deaths value is not reported in the registry record. That should not be interpreted as evidence that no deaths occurred. The safety counts describe reported events during the study; without a comparator group, they do not estimate a comparative safety difference. They also do not establish that an event was caused by treatment. Interpretation should remain limited to the recorded counts and terms.

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

The study addresses a defined research question: the change in new or newly enlarging T2 hyperintense brain MRI lesions between a baseline period and an on-treatment assessment period in pediatric participants with RRMS. It also has stated pharmacokinetic and safety objectives. Its design is open-label and single-group, with oral BG00012 given according to the listed multiple-dose regimen. These features explain what was studied, but they do not reveal the primary endpoint result.

The record does not report the mean change in lesion count, its standard deviation, a confidence interval, or a p-value. It therefore does not establish the direction, size, or precision of the primary endpoint estimate. No conclusion about whether the MRI measure changed, or how much it changed, can be drawn from the endpoint details recorded. The absence of a reported result is not evidence of no change.

Even if a within-group change estimate were available, a single-group baseline-to-treatment comparison would not be equivalent to a randomized comparison against a control group. In general, a before-and-during comparison can describe temporal change, but it cannot isolate treatment’s contribution from other changes over time as directly as a suitable concurrent comparator. This design limitation does not determine the direction of any observed result; it limits the causal comparison that can be made.

The safety summary reports participants with serious and other treatment-emergent adverse events, plus selected serious-event terms. Those summaries do not by themselves show whether events were caused by treatment or how risks compare with another group. The registry record does not report a death count.

In general, statistical evidence and clinical importance are related but distinct. An estimate may be precise without being clinically important, or important in magnitude but too uncertain for a firm conclusion. Assessing either requires results and context that are not reported in the registry record, including the primary estimate and its uncertainty. The record supports a description of the question and design, not a conclusion that the treatment works or does not work.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the distinction between measuring change and estimating a comparative treatment effect. The primary question is framed around MRI lesion change between a baseline period and an on-treatment period. That design can describe change over time within the study group, but it is not a randomized comparison. Readers should distinguish the endpoint’s measurement periods from treatment arms: the registry describes one group, not a baseline arm and a treatment arm.

The analysis population definition is also important. The primary endpoint concerns participants with new or newly enlarging T2 lesions during baseline and a post-baseline assessment. That definition narrows the target population for the primary analysis relative to a broad description of enrolled participants. Because the number analyzed is not reported in the registry record, the relationship between enrollment and the endpoint analysis cannot be quantified from this information.

The record also highlights why a registered endpoint is not the same as a posted result. The outcome is described as a mean change with a standard deviation, but those values and inferential statistics are not reported. Without them, readers cannot judge magnitude, variability, or precision. Clear outcome definitions help identify what evidence would answer the question, while complete results are needed to interpret that evidence.

Finally, the planning assumptions are explicitly illustrative and use an equal-allocation two-arm framework, whereas the study is described as single-group. This contrast matters because sample-size illustrations depend on their assumptions and do not describe the completed study’s observed power. The record is a useful example of why design, estimand, analysis population, and result reporting must be considered together, without treating one as a substitute for another.

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 principal limitation for statistical interpretation is that the numerical primary endpoint result is not reported in the registry record. The mean change and standard deviation are absent, as are a confidence interval and p-value. The outcome’s direction, magnitude, variability, and precision therefore cannot be assessed from the record.

The study is described as open-label and single-group, with no comparator. Thus, it does not provide a randomized between-group contrast. The endpoint compares distinct time periods, but the registry record does not report enough statistical detail to evaluate the exact change calculation or how time-related variation was handled. No masking is listed; further information about outcome assessment procedures is not reported in the registry record.

The primary analysis population requires baseline lesion activity and a post-baseline assessment, but its size is not reported. The record does not describe missing-data handling, exclusions, imputation, sensitivity analyses, model specification, or covariate adjustment. These omissions prevent assessment of how incomplete observations or analytic choices may have affected the endpoint estimate.

The registry describes secondary pharmacokinetic and safety objectives but does not provide their numerical results in the registry record. It does not report the statistical plan for multiplicity, interim analyses, stopping rules, or the study’s sample-size justification. The planning assumptions are illustrations and do not establish the original design rationale. The safety record includes selected event counts and terms, but the death count is not reported. These limitations constrain interpretation without indicating what the unreported findings would have been.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of the Effect of BG00012 on MRI Lesions and Pharmacokinetics in Pediatric Subjects With RRMS — NCT02410200.
• Registry record last updated 2017-10-23; status last verified 2017-09.
• Results first posted 2017-04-28.
• 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 completed, open-label, multicenter, single-group Phase 2 study of oral BG00012, or dimethyl fumarate, in pediatric participants aged 10 to 17 years with RRMS. Enrollment is listed as 22. The regimen was 120 mg twice daily for the first 7 days, followed by 240 mg twice daily for 24 weeks.

The primary outcome is change in new or newly enlarging T2 hyperintense brain MRI lesions, comparing baseline from Week -8 to Day 0 with on-treatment assessment from Week 16 to Week 24. The primary analysis population is defined by baseline lesion activity and a post-baseline assessment. The registry record does not report the numerical primary outcome result or its uncertainty.

Secondary objectives include pharmacokinetics and safety. The record reports 5 of 22 participants with serious adverse events and 19 of 22 with other treatment-emergent adverse events. A death count is not reported in the registry record. The single-group design does not provide a randomized comparator.