Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome) (NCT01415427), a randomized phase 3 study. The primary outcome is Change From Baseline in 6-minute Walk (6MW) Test - ITT.

2. Clinical Question

The clinical question is about change in walking performance during a long-term extension study, not a reported head-to-head estimate that can be interpreted from the record. The registry describes a Phase 3, randomized, quadruple-masked, parallel study of BMN 110 in people with mucopolysaccharidosis IVA. It also lists change in the 3-minute stair climb test and urine keratan sulfate among secondary outcomes, with intent-to-treat and modified per-protocol populations named for those outcomes. Those entries provide context for the study’s outcome scope, but they do not fill in the missing primary outcome result.

3. Trial Design

The registry identifies this as a Phase 3 extension study with randomized allocation, quadruple masking, and a parallel model. Its official title describes a multicenter, multinational study. The stated purpose is to evaluate long-term efficacy and safety of BMN 110 in patients with mucopolysaccharidosis IVA, also known as Morquio A Syndrome. The registry reports enrollment of 173.

The study summary describes BMN 110 at 2.0 mg/kg/week and/or 2.0 mg/kg/every other week. The arm descriptions state that the weekly regimen is an intravenous infusion administered over approximately 4 hours once a week. The every-other-week regimen is an intravenous infusion over approximately 4 hours every other week, with placebo infusions on alternating weeks. These details describe the regimens in Part 1; the registry record does not explain how every treatment period or group label relates to the extension’s full sequence.

The primary outcome timeframe is baseline to week 168. The record gives a start date of 2011-07 and a primary completion date of 2016-06-16, and lists the study status as completed. These dates describe registry milestones; they do not establish the duration of follow-up for each individual participant.

The safety record uses four group labels: PBO-QOW, PBO-QW, QOW-QOW, and QW-QW. Definitions connecting those labels to treatment histories are not reported in the registry record. Nor are details of the randomization procedure, masking procedures, treatment adherence, discontinuations, or protocol changes reported. The design labels therefore offer a broad outline but not enough information to reconstruct the full conduct of the extension study or the precise treatment contrasts for every 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

Analysis population for the primary outcome, as defined in the registry: ITT-intent-to-treat population, defined as all patients enrolled in the study who received patient IDs regardless of whether they received study drug or not.

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 6-minute Walk (6MW) Test - ITT, measured over Baseline to week 168.

The primary endpoint is change from baseline in the 6-minute walk test, measured in meters, from baseline to week 168. The registry says efficacy was assessed by changes from baseline in the 6-minute walk test. This test measures the distance a participant can walk during a timed assessment; as a continuous measure, its result can be expressed as a mean change for a defined analysis population.

Walking performance is relevant to a study of mucopolysaccharidosis IVA because it provides a functional measure that can be followed over time. In general, a repeated functional assessment can describe whether the measured capacity changes during follow-up. Its interpretation depends on the observed change, the variation among participants, the analysis population, and the handling of missing follow-up measurements.

The registry specifies the intent-to-treat population as all patients enrolled who received patient IDs, regardless of whether they received study drug. It identifies standard deviation as the dispersion measure. However, the record does not report a mean change, standard deviation, confidence interval, or test result for the primary endpoint. Without those results, the direction, magnitude, and precision of the observed change cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary endpoint as a mean change in a continuous measure and identifies standard deviation as its dispersion measure. It does not report an analysis result, so the statistical concepts below explain how such results are generally interpreted rather than describing a completed analysis from this trial.

What does a mean change represent?

In general, a mean change summarizes the average difference between participants’ baseline measurements and their later measurements. It is a summary of the group, not a description of every participant’s individual course. Participants can have different starting values and different changes, so a group mean does not show the full distribution of responses. For this study, the endpoint is change in the 6-minute walk test measured in meters, with the stated timeframe running from baseline to week 168.

The registry calls the outcome an intent-to-treat analysis and defines that population as all enrolled patients who received patient IDs, regardless of whether they received study drug. An analysis population determines which participants contribute to a result. The registry does not report how participants without a week 168 measurement were handled, or whether the stated population definition was applied consistently to an actual analysis.

What does standard deviation describe?

In general, a standard deviation describes the spread of individual measurements around their mean. A larger spread means participants’ measurements vary more widely around the average; it is not itself a measure of uncertainty in the estimated mean. The uncertainty of an estimate is commonly described with a confidence interval. The registry identifies standard deviation as the dispersion measure for the primary outcome but does not report its value or a confidence interval.

Why is a confidence interval useful?

In general, a confidence interval gives a range of values compatible with the data and the method used to calculate it. It conveys precision as well as the central estimate: a narrower interval indicates greater precision under the method’s assumptions, while a wider interval indicates less precision. It does not remove concerns about bias, missing data, or whether the analysis matches the study question. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be evaluated.

What can a significance test tell a reader?

In general, a significance test assesses how compatible observed data are with a specified statistical null model. A p-value is not the probability that a treatment is effective, nor does it quantify the size or practical importance of an effect. It should be read alongside an effect estimate and an interval estimate. The registry record gives no primary outcome p-value or analysis, so there is no reported test result to interpret.

How should the planning illustration be understood?

In general, a sample-size illustration based on an observed effect is a hypothetical planning exercise. It asks how many participants per arm might be needed under stated assumptions to detect an effect of a chosen fraction of that observed effect. It is not an account of the trial’s original design, and it is not observed power. The record describes an illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also states that the effect to detect is a stated fraction of the observed effect. The record does not report the trial’s own sample-size justification, and no primary effect estimate is reported from which such an illustration could be interpreted. The illustration should therefore not be treated as evidence about the study’s achieved power or design adequacy.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model expects. If a model underestimates variability, uncertainty estimates may be too small and inferential results may appear more precise than warranted. This is a general consideration for statistical modeling; the registry record does not report an over-dispersion assessment or a model for the primary continuous outcome.

The study record does not report the primary outcome estimates, confidence intervals, hypothesis tests, model specification, or handling of missing measurements. The statistical concepts above therefore explain what such information would mean, not what the trial’s unreported analysis found.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, but does not report analyses for them. It identifies change in the 6-minute walk test as primary and lists change in the 3-minute stair climb test and urine keratan sulfate for intent-to-treat and modified per-protocol populations among secondary outcomes. It reports six outcome measures in total and zero analyses. The primary outcome also has several categories or time points and is not reduced in the record to one comparison.

When a study examines multiple outcomes, populations, time points, or treatment contrasts, the chance of at least one apparently notable result can increase if each is tested separately without accounting for multiplicity. In general, statistical plans may address this through a prespecified hierarchy, adjustment method, or clear distinction between confirmatory and exploratory analyses. The registry record does not report a multiplicity strategy, a testing hierarchy, or which outcomes were intended as confirmatory.

Missing data are also important for a change-from-baseline outcome measured at a later visit. In general, participants may lack a follow-up measurement for many reasons, and the method used to handle those missing values can affect both the estimate and its uncertainty. The record does not report the amount or pattern of missing primary outcome data, or the method used to handle missingness.

The intent-to-treat definition is stated, but that definition alone does not establish how every enrolled participant’s data entered a particular analysis. A modified per-protocol population is named for secondary outcomes, but its membership criteria are not reported in the registry record. Without analyses, population counts, and missing-data methods, it is not possible to assess whether the results were robust to alternative analysis choices.

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: knee deformity (27.6%), poor venous access (8.9%), medical device removal (7.1%), joint instability (6.9%), vomiting (5.4%).

The registry safety record lists 173 participants at risk for serious adverse events and 89 affected. It reports one death in total, with that death assigned to the QOW-QOW group; the other listed groups have zero deaths. The record also lists participants at risk and affected by other adverse events. These are descriptive registry counts and should not be read as proof that study treatment caused an event.

The listed serious adverse event terms and percentages are knee deformity, 27.6%; poor venous access, 8.9%; medical device removal, 7.1%; joint instability, 6.9%; vomiting, 5.4%; and lower respiratory tract infection, 5.4%. The denominator and calculation details for these term-specific percentages are not reported in the registry record. They should not be treated as treatment-attributable risks or compared across groups without further information.

The group labels are PBO-QOW, PBO-QW, QOW-QOW, and QW-QW. The registry record does not fully define those labels or provide exposure-adjusted comparisons, timing, severity grades, or causal assessments for the listed events. The figures therefore describe recorded safety experience, not a complete comparative safety analysis.

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

The record establishes that a Phase 3 extension study was conducted to evaluate long-term efficacy and safety of BMN 110 in patients with mucopolysaccharidosis IVA. It identifies randomized allocation, quadruple masking, a parallel model, and enrollment of 173. It also names the primary functional outcome, defines the intent-to-treat population, and describes weekly and every-other-week dosing in Part 1. These details help characterize the study question and its broad design.

What the record does not establish is the size or direction of the primary outcome change. No mean change, standard deviation, confidence interval, or test result is reported. It is therefore not possible to quantify the reported walking-test result, describe its precision, or interpret it as evidence for a particular treatment contrast. The study’s completed status cannot substitute for those missing outcome results.

The safety record reports counts of affected participants and lists serious adverse event terms with percentages. These data are descriptive and do not establish causation. The record does not provide the event timing, treatment exposure, term-specific denominators, or a detailed comparison between regimens. A count recorded during a trial is not, by itself, an estimate of the effect of treatment on event risk.

More generally, a registry record is not necessarily a complete account of the protocol, analysis plan, or study report. Here, the treatment-group labels and the full relationship between treatment periods are not explained. The record also does not report the primary analysis, how missing measurements were handled, or how multiple outcomes were addressed. Those gaps limit the strength of any statistical conclusion drawn from the registry entry.

The appropriate reading is therefore narrow: the registry documents the trial’s stated objective, design labels, dosing descriptions, outcome definitions, and selected safety counts, while leaving the main efficacy result and its uncertainty unreported. No conclusion about the efficacy of BMN 110 follows from the endpoint title or from the fact that the study was completed.

13. Why This Trial Matters Statistically

This study raises several statistical issues common to long-term clinical trials. The endpoint is a continuous functional measure collected over an extended timeframe, and the registry identifies an intent-to-treat population. To interpret a mean change, readers need both the estimate and a measure of its uncertainty, together with a clear account of which participants contributed data. The registry record does not report those primary outcome results.

The design labels also matter. Randomized allocation and masking are relevant features for limiting some forms of bias, but labels alone do not explain how the extension’s treatment sequences worked or how the primary comparison was formed. Group labels appear in the safety record, while their full definitions are not reported. This makes it difficult to connect the listed safety counts to a clearly specified regimen contrast.

Long-term follow-up brings questions about missing measurements, treatment exposure, and changes in participant availability over time. In general, these factors can affect the meaning and precision of a change-from-baseline estimate. The registry does not report the missing-data pattern or method, so readers cannot evaluate how those issues were handled.

Multiplicity is another concern because the record names outcomes across different measures and populations. Without an analysis plan or reported results, readers cannot determine which comparisons were prioritized or how multiple testing was addressed. The sample-size material is described as a planning illustration based on an observed effect, not as the trial’s original design justification. Since the primary effect estimate is not reported, that illustration does not provide a basis for interpreting the study’s power.

The statistical importance of this record lies both in the stated design and in the limits of the available results. It shows what the study set out to assess, while also illustrating why outcome estimates, uncertainty, analysis populations, and missing-data methods are necessary for a useful quantitative 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.

The principal limitation is that the registry record does not report a numerical result or an analysis for the primary endpoint. Although the outcome, unit, timeframe, dispersion measure, and intent-to-treat definition are stated, there is no mean change, standard deviation, confidence interval, or test result. The direction, size, and precision of the primary outcome therefore cannot be assessed.

The record reports zero analyses despite listing six outcome measures. It names several secondary outcomes and populations, but does not provide numerical results for them. It also does not report a multiplicity plan, a statistical model, or whether analyses were prespecified. The record’s note that the primary outcome has several categories or time points and is not reduced to one comparison further limits a single-comparison interpretation.

Important design and analysis details are not reported in the registry record. These include the sample-size justification, interim analyses, randomization and masking procedures, missing-data methods, and criteria for the modified per-protocol population. The safety group labels are listed, but their full relationship to treatment history is not explained. Consequently, the safety counts cannot be interpreted as a complete comparative analysis by clearly defined regimen.

The adverse event information is also limited: it includes counts, a total death count, and selected serious event terms with percentages, but does not report event timing, exposure-adjusted rates, term-specific denominators, severity detail, or causal assessments. These gaps mean the figures should be read descriptively. They do not establish that treatment caused or prevented an event.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome) — NCT01415427.
• Registry record last updated 2021-07-21; status last verified 2017-04.
• Results first posted 2017-05-19.
• 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

The registry record describes NCT01415427, a completed Phase 3 extension study of BMN 110 in patients with mucopolysaccharidosis IVA, also called Morquio A Syndrome. It reports randomized allocation, quadruple masking, a parallel model, and enrollment of 173. The study summary describes weekly and every-other-week dosing, with placebo infusions on alternating weeks in the every-other-week regimen description.

The primary outcome is change from baseline in the 6-minute walk test, measured in meters from baseline to week 168, in the intent-to-treat population. The record does not report a numerical primary outcome result or an analysis. It lists secondary outcomes for the 3-minute stair climb test and urine keratan sulfate, but reports zero analyses.

The safety record reports 89 participants affected by serious adverse events among 173 at risk, and one death overall. It lists selected serious adverse event terms and percentages. The definitions of safety group labels and the details needed for comparative interpretation are not fully reported.