Study of BIIB092 in Participants With Progressive Supranuclear Palsy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of BIIB092 in Participants With Progressive Supranuclear Palsy (NCT03068468), a randomized phase 2 study. The primary outcome is Change From Baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at Week 52.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, placebo-controlled, parallel-group Phase 2 study of BIIB092 in participants with progressive supranuclear palsy. The registry records an enrollment of 490 and lists the study status as terminated. The study began on 2017-06-01, and primary completion is recorded as 2019-09-06. The reason for termination is not reported in the registry record.

During the placebo-controlled period, the BIIB092 group was assigned intravenous BIIB092 and the comparator group received matching placebo. The registry describes dosing once every 4 weeks for 48 weeks. For the open-label extension, it describes BIIB092 infusions once every 4 weeks starting at Week 52 and continuing up to Week 208, including for participants previously assigned to placebo. The record does not establish from these descriptions how many participants entered or completed the extension.

The primary efficacy assessment was change from baseline in PSPRS at Week 52. The safety objectives included deaths, serious adverse events, adverse events leading to discontinuation, and Grade 3 & 4 laboratory abnormalities. Secondary objectives and outcomes included measures of movement-related function, global change and severity, cognition, quality of life, daily activities, and phonemic fluency. The registry lists 15 outcome measures and 23 analyses.

The record does not report the randomization ratio, allocation-concealment procedure, or the reason for ending the study. It also does not report a sample-size justification or a detailed protocol for the analyses. These omissions limit what can be inferred about the original design choices and the intended analysis strategy.

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: A total of 490 participants with Progressive Supranuclear Palsy disease were enrolled and randomised in the study. Of these, 486 participants received the study drug in placebo-controlled (PC) period. After completing PC period, 416 participants entered and dosed in open-label extension (OLE) period and no participants completed the study due to early termination of the study.

Placebo-Controlled Period

Reasons for not completing this period:

Open-Label Extension Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo). 'Number of Participants Analyzed' signifies number of participants who had response on Week 52.

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: Intent-to-treat (ITT) population included randomized participants who had received at least 1 dose of blinded study treatment (BIIB092 or Placebo).

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at Week 52, measured over Baseline, Week 52.

The primary efficacy endpoint was change from baseline in the Progressive Supranuclear Palsy Rating Scale at Week 52. The PSPRS is a quantitative measure of disability in participants with PSP. Its 28 items cover History/Daily Activities, Mentation, Bulbar, Ocular Motor, Limb Motor, and Gait domains. The total score ranges from 0 (normal) to 100. A 15-item version is also described, with a total score ranging from 0 (normal) to 52. The registry record does not make clear which version is represented in the primary results description.

A positive change from baseline indicates worsening. The endpoint is used to summarize change in disability over the study period on a common scale, allowing a comparison between randomized treatment groups. The reported measure is a mean, with standard error as its dispersion measure. In general, a mean gives the average observed change in a group, while the standard error describes the precision of that estimated mean; it does not describe the spread of individual participant scores.

The Week 52 assessment is identified as the primary efficacy time point. However, the registry record does not report a single primary comparison with an estimate of the between-group difference and its uncertainty. Consequently, the endpoint definition alone does not establish the direction or size of the observed treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial’s randomized, double-blind, parallel-group design is intended to support a fair comparison between assigned treatments. Random assignment can reduce systematic differences between groups at the start of a study, on average. Blinding can reduce the influence of expectations on participant reports, clinical assessments, and decisions. These are general advantages of the design; the registry record does not describe the randomization procedure or how masking was maintained.

What does a mean change represent?

The primary outcome is a continuous score, and the registry describes its summary as a mean. A mean change represents the average difference between baseline and the follow-up measurement for the participants included in that analysis. It can be useful for comparing overall score changes, but it may not describe every participant’s experience. A group average can conceal variation in individual changes, and the clinical meaning of a difference depends on the scale and context.

The registry lists standard error as the measure of dispersion for the primary outcome. In general, standard error describes the precision of an estimated mean. It tends to be smaller when an estimate is more precise, but it is not a measure of how widely individual scores vary. A standard deviation, in contrast, describes participant-level spread. Neither the numerical mean nor its standard error for the primary endpoint is reported in the registry record.

How should a treatment contrast be read?

A between-group contrast compares the outcome in the BIIB092 group with the outcome in the placebo group. For an endpoint defined as change from baseline, interpretation requires the direction of change and the difference between groups, together with uncertainty around that difference. A confidence interval is a general way to communicate the precision of an estimate: a narrower interval indicates greater precision, while a wider interval indicates less precision. A p-value addresses compatibility of the data with a specified null hypothesis under an analysis model; it does not measure the size or clinical importance of an effect. The registry record does not provide a single primary contrast, confidence interval, or p-value for this endpoint.

The score direction matters. The registry states that positive PSPRS change indicates worsening. This convention helps readers interpret a reported change, but the available record does not give the result needed to establish the observed direction for either group or the difference between them.

Why do analysis populations matter?

The primary outcome population is described as randomized participants who received at least one dose of blinded study treatment. The record further says that the number analyzed represents participants who had a response on the Week 52 assessment. This definition is important because it does not describe an analysis of every randomized participant regardless of follow-up availability. The registry does not report how many participants lacked a Week 52 response, how missing measurements were handled, or whether additional analysis populations were used.

In general, analyzing only participants with an observed follow-up response can produce a different estimate from an analysis that accounts for missing outcomes. If missingness is related to participants’ health or outcomes, a complete-response analysis may be vulnerable to bias. Methods such as imputation or model-based approaches can address missing data under stated assumptions, but the chosen approach and its assumptions are not reported in the registry record.

What does the safety information summarize?

The registry lists counts for participants at risk, participants affected by serious adverse events, participants affected by other adverse events, and deaths in each listed group. These are descriptive summaries. General comparisons of safety require attention to the group definitions, follow-up periods, exposure, event definitions, and whether participants can contribute more than one event. The record does not provide a detailed statistical comparison of these safety outcomes or the exposure-adjusted methods, if any, used for them.

Selected serious adverse event terms are also listed with percentages. A percentage conveys how often a term was recorded in the reported data, but its interpretation depends on the denominator and event-collection rules. The record does not provide enough detail in this summary to reconstruct those rules or to determine whether the listed percentages are directly comparable across groups.

What are planning illustrations?

Any sample-size illustration based on a fraction of an observed effect is a planning exercise, not an observed trial result and not evidence of the trial’s original design assumptions. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, and a normal approximation. In general, such calculations ask how a future study might be planned under selected assumptions. They are not “observed power,” and they do not establish that the study was designed with those assumptions. The registry record does not report the trial’s own sample-size justification.

Finally, over-dispersion is a general concern when variation in data exceeds what a chosen statistical model assumes. A model that understates variability can give uncertainty estimates that are too small. Whether this issue applies depends on the outcome and model; the registry record does not identify a model for the primary endpoint or report a dispersion assessment. The posted information therefore does not support a detailed evaluation of model fit, covariate adjustment, or robustness to alternative analyses.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes and a total of 15 outcome measures and 23 analyses. These include measures of movement and daily function, global assessment, cognition, quality of life, and fluency. When a study evaluates many outcomes or makes multiple comparisons, the chance of finding at least one apparently notable result can increase. Statistical methods can control or otherwise address this multiplicity, but the method and the outcome hierarchy are not reported in the registry record.

The primary efficacy endpoint is defined at Week 52, but a single primary-outcome comparison is not reported in the registry record. The available description therefore does not establish which analysis was designated as the principal test, whether other time points or categories were part of the primary assessment, or how secondary findings were intended to be interpreted. Any isolated result among numerous analyses would need to be read in light of that missing context.

For the primary analysis, the registry describes an ITT population that included randomized participants who received at least one dose of blinded treatment. It also defines the number analyzed as those with a Week 52 response. The record does not report the extent or pattern of missing outcome data, reasons for missingness, or the method used to handle missing measurements. It does not report sensitivity analyses addressing alternative assumptions about missing data.

These gaps matter because the observed Week 52 respondents may not represent all randomized participants if response availability is related to outcome or treatment. The record does not report whether an imputation method, a repeated-measures model, or another approach was used, so no such method should be presumed. Details of protocol deviations and other analysis populations are also not reported in the registry record.

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: fall (12.7%), pneumonia aspiration (4.9%), pneumonia (3.6%), progressive supranuclear palsy (3.6%), dysphagia (3.1%).

The registry reports serious adverse event and other adverse event summaries for the placebo-controlled groups and for groups in the open-label extension. In the placebo-controlled period, the listed placebo group had 162 at risk and 52 affected by serious adverse events; the listed BIIB092 2000 mg group had 324 at risk and 88 affected. In the extension, the BIIB092 Late Start group had 137 at risk and 40 affected, while the BIIB092 Early Start group had 279 at risk and 63 affected. These are the registry’s reported group counts, not estimates of treatment effect.

Deaths are also listed: 8 in the placebo group and 16 in the BIIB092 group during the placebo-controlled period; in the extension, 10 in the Late Start group and 16 in the Early Start group. The registry record does not provide a causal assessment for these deaths. The extension groups also differ from the original placebo-controlled comparison in treatment period and group definition, so they should not be treated as a simple concurrent placebo comparison.

Among the selected serious adverse event terms, Fall is listed at 12.7%, Pneumonia aspiration at 4.9%, Pneumonia and Progressive supranuclear palsy at 3.6% each, Dysphagia at 3.1%, and Urinary tract infection at 1.9%. These terms and percentages describe reported events; they do not establish that treatment caused them. The registry summary does not give the detailed denominator or event-level analysis needed for further comparisons.

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

The record establishes the study question, the primary endpoint, the treatment groups, and a set of safety summaries. It shows that the investigators planned to compare change in PSPRS at Week 52 between BIIB092 and placebo, with positive score change defined as worsening. It also records serious adverse event counts, deaths, and selected serious event terms. These registry entries describe what the study set out to assess and what safety information is listed.

The record does not provide a single primary efficacy comparison with an effect estimate and uncertainty. It therefore does not establish the size or direction of a difference in PSPRS change between groups, nor does it indicate how precise such a difference would be. The endpoint definition, trial design, and enrollment figure cannot replace the missing comparative result.

The listed safety counts are descriptive and should not be read as proof that an event was caused by BIIB092 or by placebo. A causal safety assessment would require careful consideration of treatment exposure, follow-up, event definitions, and the comparison plan. The registry’s terminated status does not explain why the study ended and is not itself evidence about efficacy or safety.

Likewise, the presence of secondary outcome measures does not establish that they showed benefit or harm. The registry record does not provide the multiplicity plan or the details needed to assess how missing Week 52 responses were handled. Statistical interpretation of any outcome depends on the analysis method and its assumptions, not only on the name of the measurement scale.

The most defensible reading is therefore limited: this was a randomized, double-blind, placebo-controlled study with a defined Week 52 PSPRS endpoint and reported safety counts, but the registry information does not provide a single primary efficacy result. It cannot support a conclusion about whether BIIB092 changed PSPRS outcomes relative to placebo.

13. Why This Trial Matters Statistically

This study is statistically important because it illustrates the difference between a clearly defined research question and a result that can be interpreted quantitatively. The registry specifies a randomized, double-blind, parallel-group comparison and names a primary clinical scale and assessment time. Those design features make clear what kind of treatment contrast was intended. Yet without a reported primary estimate and its uncertainty, the central comparative question cannot be answered from the registry record.

The endpoint also highlights why measurement direction and scale structure matter. PSPRS is a multi-domain disability measure, and positive change is defined as worsening. A reader interpreting any reported group means would need to know the relevant scale version, the analysis population, and the between-group contrast, rather than relying on within-group change alone.

The record further illustrates the importance of transparency about missing data and multiplicity. It lists numerous outcomes and analyses, but does not report the analysis plan for controlling or interpreting multiple comparisons, nor how absent Week 52 responses were handled. Such details affect how much confidence can be placed in estimates and how secondary findings should be weighed.

Finally, the safety summaries show why event counts require context. Treatment period, group definition, exposure, and the distinction between serious events, other events, and deaths all matter. The extension groups are not equivalent to the placebo-controlled comparison. Clear reporting of these design and analysis details is essential for separating descriptive records from comparative evidence.

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 limitations constrain interpretation of this registry record. The status is listed as terminated, but the reason for termination is not reported in the registry record. The timing of primary completion is recorded, but the available information does not explain how termination related to recruitment, treatment, follow-up, or analysis. No explanation should be inferred from status alone.

The primary outcome is described using the PSPRS, including both a 28-item and a 15-item version, but the registry summary does not make clear which version is represented in the primary results description. The record identifies mean and standard error as the summary approach but does not give a single primary between-group estimate, confidence interval, or p-value. The posted material therefore cannot establish the numerical efficacy result or its precision.

The outcome population includes randomized participants who received at least one dose, with the analyzed number defined by having a Week 52 response. The record does not report the number or characteristics of participants without that response, reasons for missing assessments, or the missing-data method. It also does not provide sensitivity analyses to show whether conclusions would be robust to different assumptions.

Although multiple outcomes and analyses are listed, the registry record does not report the statistical plan for multiplicity, covariate adjustment, or model selection. It does not describe a sample-size justification or interim analyses. The safety summaries do not provide the detailed event definitions, exposure-adjusted comparisons, or causal assessments needed to interpret group differences as treatment-related. These omissions limit both efficacy and safety interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of BIIB092 in Participants With Progressive Supranuclear Palsy — NCT03068468.
• Registry record last updated 2020-12-21; status last verified 2020-11.
• Results first posted 2020-12-21.
• 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

NCT03068468 is a randomized, double-blind, placebo-controlled, parallel-group Phase 2 study of BIIB092 in participants with progressive supranuclear palsy. The registry records enrollment of 490 and lists the status as terminated. Study start is recorded as 2017-06-01, with primary completion on 2019-09-06.

The primary efficacy endpoint was change from baseline in PSPRS at Week 52, with positive change indicating worsening. The registry describes a blinded placebo-controlled treatment period followed by an open-label extension in which both groups were to receive BIIB092. It lists multiple secondary outcomes and reports selected safety counts and serious adverse event terms.

A single primary-outcome comparison, its uncertainty, the reason for termination, the missing-data approach, and the multiplicity strategy are not reported in the registry record. The record therefore documents the study design and outcome framework but does not provide enough information to interpret a numerical primary efficacy contrast.