Safety and Efficacy of BAF312 in Dermatomyositis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of BAF312 in Dermatomyositis (NCT02029274), a randomized phase 2 study. The primary outcome is Change From Baseline in Manual Muscle Testing - 24 Muscles (MMT-24) Score.

2. Clinical Question

This is a dose-response study question, rather than simply a question about whether any BAF312 dose differs from placebo. The study description states that it sought to investigate the relationship between dose and efficacy and safety and to determine the minimum dose required for a maximal clinical effect. Those aims require interpretation across the dose groups, while the posted primary comparisons present each dose against placebo.

The registry describes a treatment period of 6+6 months, with Period 1 involving different daily doses or placebo and Period 2 using BAF312 at 2 mg daily. The primary endpoint timeframe is baseline to 6 months, so the posted primary comparisons concern the Period 1 assessment. The registry record does not report a primary endpoint comparison for the later period.

The trial was randomized, triple-masked, and parallel, and its status is terminated. The registry record does not report why the trial was terminated. It also does not report a protocol-level explanation of how the dose-response question was to be assessed statistically. Consequently, the posted comparisons can be described, but the broader intended dose-response decision process cannot be reconstructed from the record.

3. Trial Design

This was a Phase 2 randomized, triple-masked, parallel-group study of BAF312 and placebo in active dermatomyositis. The official title describes a double-blind, randomized, placebo-controlled study evaluating safety, tolerability, efficacy, and preliminary dose response. The registry lists Novartis Pharmaceuticals as sponsor and identifies the status as terminated.

The trial description identifies 2 treatment periods. During Period 1, participants received BAF312 at daily doses of 0.5 mg, 2 mg, or 10 mg, or matching placebo. The dose groups were uptitrated to their assigned daily dose over a 10 day period, and treatment continued for up to 24 weeks. During Period 2, the described treatment was BAF312 at 2 mg daily, following uptitration. The registry describes the overall treatment period as 6+6 months.

For the primary MMT-24 endpoint, the posted group summaries are for BAF312 0.5mg, BAF312 2mg, BAF312 10 mg, and Placebo. Their reported analysis counts are 3, 4, 3, and 3, respectively. The study enrollment is 17, but the registry record does not explain the relationship between enrollment and the counts contributing to each endpoint summary. Those counts should therefore be read as analysis counts for the posted endpoint, not as a complete account of participant flow.

The primary endpoint was change from baseline in the MMT-24 score, assessed at baseline and 6 months. The registry reports 3 repeated-measures comparisons, each contrasting one BAF312 dose group with placebo. It also lists secondary outcomes for BAF312 plasma concentration, peripheral blood lymphocyte counts, MMT-24 change, and 6-MWD change. The registry record does not report the reason for termination, the planned enrollment target, or details of the randomization procedure beyond identifying the study as randomized.

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: Participants were randomized to each treatment group in a1:1:1:1 ratio.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The pharmacodynamic (PD) analysis set, which included all randomized participants, was considered for the analysis. Participants with valid baseline MMT24 score and at least one valid post baseline MMT24 score were included in the analysis.

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 From Baseline in Manual Muscle Testing - 24 Muscles (MMT-24) Score, measured over Baseline, 6 months.

The primary endpoint was change from baseline in the Manual Muscle Testing-24 (MMT-24) score at 6 months. Each tested muscle was scored on a 0 - 10 scale, where 0 indicated the weakest muscle score and 10 indicated the strongest. The total score ranged from 0 - 240. A positive change from baseline indicates improvement, so the endpoint expresses change in measured muscle strength rather than a direct count of clinical events.

MMT-24 is used in this trial as a continuous measure of muscle function. A continuous endpoint retains information about the degree of change in a score, rather than reducing results to a binary category such as improved or not improved. The registry reports least-squares means and standard errors for the dose groups. Least-squares means are model-based group estimates; the record identifies repeated-measures analysis for the reported treatment comparisons.

For clinical interpretation, the direction of a change matters: positive within-group change corresponds to improvement according to the registry’s definition. A between-group contrast asks whether change differs between a BAF312 dose and placebo; it is not the same as asking whether either group changed from its own baseline. The posted comparison estimates are net mean differences, with confidence intervals that express uncertainty around those contrasts.

The registry record does not report a threshold for a clinically important MMT-24 change. Thus, the score scale and direction can be described, but the posted values cannot be classified against a registry-reported threshold for meaningful benefit.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a change in MMT-24 score from baseline to 6 months. The registry reports least-squares means with standard errors for each group and repeated-measures analyses for the dose-versus-placebo comparisons. These are distinct statistical summaries. The group means describe estimated change within each arm, whereas each mean difference (net) estimates a contrast between a BAF312 dose group and placebo.

What does a least-squares mean describe?

A least-squares mean is a model-based estimate of a group mean. It is not necessarily identical to the simple arithmetic mean of the observed endpoint values, because the analysis model may account for structure in the repeated measurements. The registry identifies the estimates as least-squares means but does not report the complete model specification, covariates, covariance structure, or other implementation details. It is therefore possible to describe the estimates as model-based, but not to infer precisely how every model term was handled.

The standard error describes the estimated uncertainty of a mean estimate. It is not the spread of individual participant scores. A standard error is useful for understanding precision: larger standard errors, in relation to the estimate, imply less precision. Because the endpoint analysis counts are limited, the reported standard errors and confidence intervals deserve close attention alongside the point estimates.

How should the between-group contrasts be read?

A mean difference (net) is a contrast between the estimated change in one dose group and estimated change in placebo. A contrast near zero indicates little estimated separation between the groups, while a negative or positive value indicates the direction defined by the comparison’s coding. In this registry, the reported values are 0.551 for BAF312 0.5mg versus placebo, -15.368 for BAF312 2mg versus placebo, and -13.709 for BAF312 10 mg versus placebo. The endpoint scale defines positive change within a group as improvement, but interpretation of a contrast should rely on the comparison as reported rather than treating each group’s change as a treatment effect by itself.

The reported 95% confidence interval gives a range of values compatible with the analysis under its assumptions. It is not a guarantee that the true contrast lies within the interval, nor does it state the probability that a particular treatment effect is true. All three reported intervals include zero: -22.447 to 23.549, -37.128 to 6.391, and -36.806 to 9.388. Their breadth signals that the contrasts are estimated imprecisely. The interval is often more informative than a threshold-based reading of a p-value because it conveys both direction and a range of plausible contrast magnitudes.

The registry reports p-values of 0.962, 0.164, and 0.241 for the respective comparisons. A p-value assesses how compatible the observed data are with a specified null model, given the analysis assumptions. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. Here, the p-values accompany wide confidence intervals, and should not be taken as evidence that the treatment groups are equivalent. An equivalence conclusion would require an explicitly stated margin and an appropriate analysis; such a margin is not reported in the registry record.

What does repeated-measures analysis address?

Repeated-measures analysis is a general approach for outcomes measured more than once on the same participant. It can use the pattern of repeated observations and account for their correlation, rather than treating every measurement as independent. The general statistical rationale is that measurements from the same person tend to be related. A suitable model can represent that dependence and estimate group differences over time. The registry names repeated-measures analysis but does not report the full model, assumptions, treatment-by-time terms, or how missing visits were handled. Those details cannot be reconstructed from the method label alone.

Repeated-measures models also depend on assumptions about the outcome distribution, covariance, and missingness. For example, the interpretation of model estimates can depend on whether the assumed relationship among repeated measurements is adequate. The registry record does not describe diagnostic checks or sensitivity analyses. The reported results therefore represent the stated analysis, while the robustness of the estimates to alternative modeling choices is not reported in the registry record.

What are the planning illustrations for?

Sample-size calculations based on an observed effect are planning illustrations, not observed power. The stated assumptions for such illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These assumptions describe a hypothetical planning exercise; they do not establish that the trial was designed using those assumptions or that the trial had a particular probability of detecting an effect. The registry record does not report the trial’s original sample-size justification. Numerical planning outputs are not reported in the registry record.

More generally, a small study can produce broad confidence intervals even when its point estimate appears sizable. A planning calculation based on an observed effect can also be optimistic because the observed estimate is uncertain. Sample-size illustrations should therefore be read as conditional scenarios, not as retrospective proof that a trial was adequately or inadequately powered. The registry record does not provide a basis for determining the original design’s power or planned detectable difference.

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("BAF312 0.5mg", "BAF312 2mg", "BAF312 10 mg", "Placebo")
n   <- c(3, 4, 3, 3)
m   <- c(28.286, 12.367, 14.026, 27.735)
sp  <- c(8.1539, 7.0967, 8.1541, 8.2175)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  BAF312 0.5mg  3  28.286  14.123  -6.797  63.369
CARM  BAF312 2mg  4  12.367  14.193  -10.218  34.952
CARM  BAF312 10 mg  3  14.026  14.123  -21.058  49.110
CARM  Placebo  3  27.735  14.233  -7.622  63.092

11. Analyses Reported by the Sponsor

The registry reports sponsor analyses using repeated-measures analysis for the primary endpoint comparisons. These are the principal inferential results available for the dose-versus-placebo contrasts: the reported net mean differences, 95% confidence intervals, and p-values. The analysis estimates and uncertainty should be interpreted together, with the confidence intervals conveying the breadth of uncertainty around each contrast.

The registry record does not report a separate recalculated contrast or a recalculated confidence interval alongside the sponsor’s results. Accordingly, there is no independent recalculation to compare with the sponsor analysis in the posted record. The reported group means and standard errors are not, by themselves, sufficient to reproduce the repeated-measures analysis, since the model specification and participant-level repeated measurements are not reported.

The sponsor’s own analysis is the relevant reported analysis for these comparisons. Its results do not show a narrow estimate that resolves the direction or magnitude of the dose-versus-placebo differences: each reported 95% confidence interval includes zero and extends across values on both sides. The registry record does not provide the model details needed to independently verify those estimates, nor does it report a separate analysis that reconciles alternative methods. The interpretation should therefore stay with the reported sponsor contrasts and their stated uncertainty, without treating an unreported recalculation as a competing result.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 reported primary endpoint comparisons: each of the BAF312 dose groups is compared with placebo. It also lists secondary outcomes for plasma concentration, peripheral blood lymphocyte counts, MMT-24 change, and 6-MWD change. The record does not report whether the statistical plan adjusted for multiple comparisons, whether a testing hierarchy was prespecified, or whether the primary comparisons were intended to share a single overall type I error rate. Without that information, the reported p-values should be read as individual comparison results, not as evidence that multiplicity was controlled.

The primary analysis population is described as the pharmacodynamic analysis set. The registry says that all randomized participants were considered for this analysis, and that participants with a valid baseline MMT-24 score and at least one valid post-baseline score were included. This identifies an analysis population rule, but it does not establish that every randomized participant contributed to every reported estimate. The group counts for the primary endpoint are 3, 4, 3, and 3 for BAF312 0.5mg, BAF312 2mg, BAF312 10 mg, and placebo, respectively.

The registry record does not report the number or reasons for missing primary endpoint observations, the amount of missingness by visit, or the assumptions used to handle missing data. It does not report imputation procedures, sensitivity analyses for missing outcomes, or a comparison of included and excluded participants. Repeated-measures analysis can use available repeated observations under model assumptions, but the method label alone does not identify the missing-data assumptions used in this trial. The robustness of the results to missing data is therefore not reported in the registry record.

The record also does not report whether outcome analyses were prespecified in a statistical analysis plan, whether interim analyses were conducted, or whether any subgroup analyses were planned. These omissions limit assessment of selective reporting and the full analysis strategy. They do not change the posted numerical results, but they constrain how confidently those results can be interpreted as the complete prespecified inferential picture.

13. 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: laceration (25.0%), procedural pain (25.0%), subarachnoid haemorrhage (25.0%), syncope (25.0%), pulmonary embolism (25.0%).

The registry reports serious adverse events and other adverse events separately for Period 1 and Period 2 treatment groups. In Period 1, serious adverse events were reported for 1 participant in the placebo group, 0 in the BAF312 0.5 mg/day group, 0 in the BAF312 2 mg/day group, and 1 in the BAF312 10 mg/day group. The corresponding numbers at risk were 5, 4, 4, and 4. The registry also reports other adverse events affecting 1, 1, 4, and 4 participants in those groups, respectively.

For Period 2, the registry reports 0 serious adverse events among 5 at risk in the placebo /BAF312 2 mg/day group, 0 among 4 at risk in the BAF312 0.5 mg/day/BAF312 2 mg/day group, 1 among 4 at risk in the BAF312 2 mg/day/BAF312 2 mg/day group, and 1 among 4 at risk in the BAF312 10 mg/day/BAF312 2 mg/day group. Other adverse events affected 2, 1, 4, and 2 participants in these groups, respectively.

These are counts within the stated groupings and periods, not adjusted comparisons of risk. The Period 2 groups reflect treatment sequences, so they should not be treated as if they were independent new randomized arms without further information. The registry lists serious-event terms with percentages, including Laceration, Procedural pain, Subarachnoid haemorrhage, Syncope, Pulmonary embolism, and Pneumonia; the denominator and basis for these term percentages are not reported in the registry record. Death counts are not reported in the registry record. The counts alone do not establish causation or support a comparative safety conclusion.

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

The posted results describe changes in a muscle-strength score and estimated contrasts between BAF312 dose groups and placebo. Positive change in MMT-24 is defined as improvement, and the reported group-level least-squares mean changes are positive for all four groups. The dose-versus-placebo contrasts are much less precise than a simple reading of the point estimates might suggest: all three confidence intervals include zero and extend to values on either side of it.

This means the registry’s primary endpoint results do not precisely resolve how the BAF312 groups differed from placebo. The estimates are compatible with a range of contrast values, and the analysis counts are limited. The p-values should not be translated into a probability that the treatment is effective or ineffective. Nor do these results establish that the groups are equivalent, since the registry record does not report an equivalence margin or an equivalence analysis.

The study description says that the trial was intended to examine dose response and identify the minimum dose required for maximal clinical effect. The posted dose-versus-placebo contrasts do not, by themselves, establish a dose-response pattern or identify such a dose. The registry record does not report a dedicated overall dose-response test, a clinically important change threshold, or a formal decision rule for selecting a dose.

The results also do not answer every question about the trial. The registry reports a primary assessment at 6 months, and a later treatment period is described, but the posted primary comparisons do not provide a corresponding primary endpoint contrast for that later period. The record does not report the reasons for termination, complete participant flow, or enough detail to assess missing-data sensitivity. Safety counts are descriptive and do not establish that an event was caused by treatment or that risks differ reliably between groups.

Accordingly, the most defensible reading is limited: the registry reports model-based primary endpoint estimates and repeated-measures dose comparisons with substantial uncertainty. Those findings should be distinguished from conclusions about clinical benefit, treatment selection, or comparative safety, which cannot be established from these posted data alone.

15. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between a point estimate and the precision of that estimate. The group means suggest changes in MMT-24, but the clinically relevant comparison is the difference in change between each BAF312 dose group and placebo. The confidence intervals for those contrasts are wide and include zero. Focusing only on the group means or on the sign of a contrast would miss the uncertainty conveyed by the inferential results.

The study also highlights the challenge of evaluating dose response with limited endpoint analysis counts across several dose groups. A pattern across dose estimates can be suggestive descriptively, but it is not equivalent to a formal test of dose response. The registry record describes dose response as an objective, yet the reported primary results are separate dose-versus-placebo comparisons. An overall dose-response conclusion cannot be inferred solely from that set of contrasts.

The endpoint makes the choice of estimand important. Within-group change describes how the score changed from baseline in an arm; a between-group contrast estimates how that change differed from placebo. These answer different questions. The registry supplies both kinds of summary, but interpretation should prioritize the between-group contrasts when assessing comparative treatment effects.

Finally, the record demonstrates why reporting analysis populations, missing-data handling, multiplicity procedures, and model details matters. Those details affect how the estimates can be evaluated and reproduced. Their absence does not invalidate the posted findings, but it limits independent assessment of assumptions and the broader inferential strategy. In a small terminated study, clear reporting of uncertainty and analysis context is especially important.

16. 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 primary endpoint analysis counts are small, and the confidence intervals for the treatment contrasts are broad. As a result, the reported estimates have limited precision and are sensitive to the information contributed by individual observations. Participant-level data are not reported, so the effect of individual values on the estimates cannot be assessed.

The registry identifies repeated-measures analysis but does not report the full statistical model, its covariance structure, model diagnostics, or all adjustment variables. It also does not describe how missing measurements were handled, give missingness counts by group and visit, or report sensitivity analyses. These omissions make it difficult to judge whether alternative reasonable modeling or missing-data assumptions would materially change the results.

The record does not report adjustment for multiple testing, a testing hierarchy, or an overall dose-response test. Since the trial had multiple dose-versus-placebo comparisons and listed secondary outcomes, the absence of this information limits interpretation of the individual p-values as a complete inferential strategy. A clinically important MMT-24 threshold is also not reported, so statistical estimates cannot be mapped to a registry-defined threshold for meaningful change.

The trial is listed as terminated, but the reason is not reported in the registry record. Enrollment is reported as 17, while the endpoint analysis counts are smaller; the record does not provide a full participant disposition that explains the difference. The treatment descriptions include two periods, but the posted primary results focus on the baseline-to-6-month assessment and do not provide a primary comparison for the later period.

Safety figures are presented as counts for treatment periods and sequences, without a reported comparative analysis. The denominator and basis for the listed serious-event term percentages are not reported in the registry record, and death counts are not reported in the registry record. These limitations mean that the safety summaries are descriptive and should not be used to infer comparative risks or causation.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Safety and Efficacy of BAF312 in Dermatomyositis — NCT02029274.
• Registry record last updated 2021-01-05; status last verified 2018-12.
• Results first posted 2019-01-15.
• 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.

20. Record Summary

NCT02029274 is a Phase 2 randomized, triple-masked, parallel-group study of BAF312 and placebo in active dermatomyositis, sponsored by Novartis Pharmaceuticals. The registry reports enrollment of 17 and lists the study status as terminated. The study description covers 2 treatment periods and identifies BAF312 daily doses of 0.5 mg, 2 mg, and 10 mg during Period 1, followed by BAF312 at 2 mg daily during Period 2.

The primary endpoint was change from baseline in MMT-24 score at 6 months. The registry reports least-squares mean changes and repeated-measures dose-versus-placebo comparisons. All three reported 95% confidence intervals include zero and are broad. The endpoint analysis counts are 3, 4, 3, and 3 across the BAF312 0.5mg, BAF312 2mg, BAF312 10 mg, and placebo groups.

The record lists secondary outcomes and adverse-event counts, but does not report the reason for termination, detailed missing-data methods, multiplicity procedures, or a complete model specification. The posted primary estimates should therefore be read as uncertain registry-reported results rather than as a definitive dose-response or clinical conclusion.