This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for BMN 701 Phase 3 in rhGAA Exposed Subjects With Late Onset Pompe Disease (INSPIRE Study) (NCT01924845), a na phase 3 study. The primary outcome is Percent Predicted Maximum Inspiratory Pressure (MIP).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01924845 |
| Phase | Phase 3 |
| Condition | Late-onset Pompe Disease |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | n/a |
| Lead sponsor | BioMarin Pharmaceutical |
| Results posted | Yes |
2. Clinical Question
Population
Ambulatory participants with late-onset Pompe disease who had received recombinant human acid alpha-glucosidase (rhGAA) for 48 weeks or longer and had mild to moderate respiratory impairment. The registry lists enrollment of 24 participants.
Intervention
BMN 701, a GILT-tagged recombinant human GAA, given by intravenous infusion at 20 mg/kg every other week. The planned initial treatment period was 24 weeks, followed by an optional extension.
Comparator
There was no separate comparison group. The design was single-group, with all participants receiving active drug after switching from their existing rhGAA treatment.
Primary question
What was the mean percent-predicted maximum inspiratory pressure (MIP) at baseline and Week 24 in the full analysis set? The registry record identifies this outcome but does not report its numerical results.
The study was intended to examine respiratory function after a direct switch to BMN 701 among people already exposed to rhGAA. Because participants did not continue in a separate control group, the main within-study description is the change in the primary respiratory measure between baseline and Week 24. The registry record does not report the mean values, the change from baseline, variability estimates, confidence intervals, or a statistical test for that comparison.
The clinical question is therefore narrower than whether BMN 701 performs better than continued rhGAA. Without a concurrent control group, the study cannot directly distinguish a treatment-related change from changes that might occur over time for other reasons. The registry record also does not report the reason the study was terminated or whether the planned treatment and extension periods were completed by participants.
3. Trial Design
This was a Phase 3, single-group, open-label switchover study, listed as NCT01924845 and titled the INSPIRE Study. BioMarin Pharmaceutical is listed as the sponsor. The registry gives a start date of 2014-04, primary completion of 2016-09-12, enrollment of 24, and a status of terminated. The reason for termination is not reported in the registry record.
Eligible participants described in the study summary were ambulatory, had late-onset Pompe disease, had mild to moderate respiratory impairment, and had been receiving rhGAA for 48 weeks or longer. Participants switched directly to BMN 701, with the study summary stating that no dose of existing therapy would be missed. The listed regimen was BMN 701 20 mg/kg by intravenous infusion every other week for 24 weeks, followed by an optional extension of 240 weeks, for a stated total therapy duration of 264 weeks.
Allocation is listed as not applicable, masking as none, and the model as single group. Those features mean that the study did not use random assignment to BMN 701 and a concurrent control treatment, and participants and investigators were not masked to treatment. All participants were to receive active drug. The design can describe outcomes observed after the switch, but it does not provide a randomized comparison against continued rhGAA or another control.
The primary outcome was percent-predicted maximum inspiratory pressure, assessed at baseline and Week 24. Listed secondary outcomes were percent-predicted maximum expiratory pressure, the 6 Minute Walk Test in meters, percent-predicted upright forced vital capacity, and the number of participants with non-serious adverse events. The registry record lists five outcome measures overall, but reports zero analyses. Numerical results for the efficacy outcomes are not reported in the registry record.
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: The study consisted of a 31-day Screening and Baseline Period (26-day Screening Period, a 5-day Baseline/Enrollment Period), a 24-week Treatment Period, and a 30-day Safety Follow-up Period. Following the Screening and Baseline assessments, qualified subjects were enrolled in the study.
Overall Study
| Stage | BMN 701 20 mg/kg |
|---|---|
| STARTED | 24 |
| COMPLETED | 18 |
| NOT COMPLETED | 6 |
Reasons for not completing this period:
| Reason | BMN 701 20 mg/kg |
|---|---|
| Adverse Event | 3 |
| Withdrawal by Subject | 2 |
| Protocol Violation | 1 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set. Please note the Overall Number of Participants reflects the number of patients in the Analysis Population, while the Number Analyzed of patients at specific visit in the Outcome Measure Table reflects the participants who had data at that visit .
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.
| Characteristic | Unit | BMN 701 20 mg/kg |
|---|---|---|
| Participants analysed | 24 | |
| Age, Continuous | years | 47.9 (SD 13.27) |
| Age, Customized: 18-65 | Participants | 22 |
| Age, Customized: > 65 | Participants | 2 |
| Sex: Female, Male: Female | Participants | 12 |
| Sex: Female, Male: Male | Participants | 12 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 24 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 0 |
| Race/Ethnicity, Customized: Asian | Participants | 0 |
| Race/Ethnicity, Customized: Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race/Ethnicity, Customized: Black or African American | Participants | 0 |
| Race/Ethnicity, Customized: White | Participants | 24 |
| Race/Ethnicity, Customized: Other | Participants | 0 |
| Region of Enrollment: Belgium | Participants | 1 |
| Region of Enrollment: Germany | Participants | 9 |
| Region of Enrollment: United Kingdom | Participants | 7 |
| Region of Enrollment: United States | Participants | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Percent Predicted Maximum Inspiratory Pressure (MIP), measured over Baseline, Week 24.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Percent Predicted |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is percent-predicted maximum inspiratory pressure (MIP), a pulmonary function measure. MIP assesses the pressure a person can generate while inhaling against resistance and is used to characterize inspiratory respiratory muscle function. Reporting it as a percent-predicted value expresses the measured pressure relative to a predicted reference. The registry record does not describe the reference equation or the details of how the predicted value was calculated.
The endpoint is listed as a mean with standard deviation, with assessments at baseline and Week 24. A comparison across those visits can describe whether the group’s average measured MIP changed during the initial treatment period. The standard deviation describes how dispersed individual measurements are around the mean; it does not by itself quantify the precision of the estimated mean or the uncertainty in a change between visits.
The record identifies the full analysis set as the population for this outcome. It also notes that the overall participant count reflects the analysis population, while the number analyzed at a specific visit reflects participants with data at that visit. The visit-specific counts and the MIP values are not reported in the registry record. Consequently, the size and direction of any observed change, and its precision, cannot be assessed from the registry information available.
As a general statistical point, a physiological measure can be informative about a particular aspect of function without representing every aspect of a condition or a participant’s overall experience. MIP is the designated primary measure; it should be interpreted as a respiratory-function endpoint rather than as a complete account of clinical status.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record specifies a primary outcome, a population, and assessment times, but it does not provide numerical results for the primary outcome. It therefore does not establish what mean MIP was at baseline or Week 24, whether the mean changed, or how variable measurements were. No effect estimate, confidence interval, or p-value for the primary outcome is reported in the registry record. The primary efficacy result cannot be characterized as an increase, a decrease, or no change from the information recorded.
The design is important for interpreting any within-group change that might be reported elsewhere. Participants switched from prior rhGAA treatment to BMN 701, but there was no concurrent control group. A before-and-after comparison can describe what happened in the study group over time; by itself, it cannot separate the effect of the switch from time-related changes, measurement variation, or other influences. The open-label design also means that participants and investigators knew the treatment being received. The registry record does not report procedures intended to limit potential effects of that knowledge on assessment or reporting.
The study population was selected: participants were ambulatory and had mild to moderate respiratory impairment, and they had prior rhGAA exposure for 48 weeks or longer. Findings from such a group would not automatically describe people with different disease features or treatment histories. The registry record does not provide further detail about participant characteristics or the number with evaluable MIP data at each visit.
For safety, the record lists 24 participants at risk for serious adverse events and 10 participants affected. It lists 24 at risk for other adverse events and 23 affected, and reports zero deaths. These are counts of participants, not a measure of whether treatment caused an event. The record does not provide a comparator group, event rates adjusted for time at risk, or a causal assessment in the information summarized for these figures. Six serious-event terms are listed, each with a reported percentage of 4.2%; the record does not provide enough detail in these entries to infer that the terms were mutually exclusive or to derive a broader risk estimate.
The registry status is terminated. That status alone does not explain why the study ended, whether the initial period was completed as planned, or whether the optional extension proceeded as intended. The reason for termination and the numerical efficacy analyses are not reported in the registry record. Accordingly, the record supports a description of the study design and listed safety counts, but it does not support a conclusion about the size or precision of the primary efficacy result.
9. Statistical Methods Explained
The registry identifies the primary measure as a continuous outcome summarized by a mean and standard deviation. It is percent-predicted maximum inspiratory pressure, measured at baseline and Week 24 in the full analysis set. The record does not report the observed means, standard deviations, visit-specific participant counts, change estimate, confidence interval, or p-value. The method used to compare the visits is not reported in the registry record.
What does a mean describe?
As a general statistical concept, a mean gives the arithmetic average of measurements in a group. It can provide a concise description of the group’s central value, but it does not show whether individual participants had similar values or widely differing ones. The standard deviation describes the spread of individual observations around the mean. A standard deviation is not the same as a standard error or a confidence interval: it describes variability among observations, whereas uncertainty in an estimated mean also depends on how many observations contribute and on the analysis method.
What would a confidence interval add?
As a general explanation, a confidence interval gives a range of values compatible with the data under a specified statistical procedure. It communicates uncertainty around an estimate rather than only its point value. A narrow interval indicates greater precision than a wide interval, but interpretation also depends on the outcome, study design, and analysis. No confidence interval for MIP or its change is reported in the registry record, so the precision of the primary outcome estimate cannot be evaluated from this record.
Why does the single-group design matter?
In a randomized comparison, treatment groups can provide a concurrent reference for changes over the same period. This study is listed as single-group, with allocation not applicable and no masking. Participants all switched to BMN 701. A comparison between baseline and Week 24 would therefore be a within-group description, not a randomized estimate of the difference between BMN 701 and continued prior treatment. General statistical interpretation of uncontrolled before-and-after data must allow for other explanations for change, including natural variation over time and differences in who has an available measurement at each visit.
The record states that the analysis population count may differ from the number analyzed at a specific visit because the visit count includes participants with data at that visit. This distinction matters: an outcome mean at a visit is based on observed values for participants contributing data there, and the available participants need not be identical across visits. The record does not give the visit-specific counts or explain how missing measurements were handled. It is therefore not possible to assess whether the set of observed measurements changed over time or how missing data affected the estimate.
What does over-dispersion mean?
As a general statistical concept, over-dispersion occurs when observed variation is greater than a statistical model assumes. It matters because a model that understates variation can produce uncertainty estimates that are too small. The primary endpoint is described using a mean and standard deviation, but the registry record does not report a model, an over-dispersion assessment, or a method for handling it. No claim about over-dispersion in this study can be made from the record.
How should planning calculations be read?
Any planning illustration based on an observed effect is distinct from the trial’s actual design and from an observed study result. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. The trial itself had a single group and no randomized comparator. Thus, a two-arm planning setup does not describe how participants were allocated in this study. Planning sample sizes are hypothetical design quantities, not observed power and not evidence that a result was statistically significant. The registry record does not report the trial’s own sample-size justification or statistical analysis plan.
The registry lists zero analyses. That entry should not be treated as a numerical finding about MIP; it means that analyses are not presented in the registry information summarized for this study. The primary numerical outcome and its uncertainty are not reported in the registry record. Without those estimates and the analysis details, statistical significance, precision, and the magnitude of any change cannot be assessed.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary outcome and several secondary outcomes: percent-predicted maximum expiratory pressure, the 6 Minute Walk Test in meters, percent-predicted upright forced vital capacity, and the number of participants with non-serious adverse events. It reports five outcome measures overall and zero analyses. Numerical efficacy results and inferential tests for these outcomes are not reported in the registry record.
Multiplicity is the statistical issue that arises when several outcomes, time points, or comparisons are assessed. As a general concept, conducting many tests can increase the chance of at least one apparently notable result arising by chance. A prespecified primary endpoint and a documented approach to secondary analyses can help readers understand which results were confirmatory and how multiple comparisons were handled. The registry record does not report a multiplicity-adjustment method, a hierarchy for testing outcomes, or a statistical analysis plan. It is not possible to determine whether or how multiplicity was addressed.
The registry identifies the full analysis set for the primary endpoint and distinguishes the overall analysis population from the participants with data at a specific visit. However, visit-specific counts, reasons for missing measurements, and the method used to handle missing data are not reported in the registry record. The record does not state whether analyses used only observed cases, imputed missing values, or applied another approach. The impact of missing data on the estimated outcome therefore cannot be assessed.
The treatment of participants who discontinued, and whether follow-up differed between participants, is also not reported in the registry record. The terminated status does not by itself establish how much follow-up was available or why the study ended. These omissions limit interpretation of both the efficacy outcomes and the completeness of safety follow-up.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| BMN 701 20 mg/kg | 10 | 24 | 41.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| BMN 701 20 mg/kg | 0 of 24 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| BMN 701 20 mg/kg | 23 of 24 |
Most frequent serious adverse event terms
| Event term | Organ system | BMN 701 20 mg/kg |
|---|---|---|
| Atrial fibrillation | Cardiac disorders | 1 of 24 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 24 |
| Anaphylactic reaction | Immune system disorders | 1 of 24 |
| Fall | Injury, poisoning and procedural complications | 1 of 24 |
| Blood creatine phosphokinase increased | Investigations | 1 of 24 |
| Hypoglycaemia | Metabolism and nutrition disorders | 1 of 24 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 1 of 24 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 1 of 24 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 1 of 24 |
| Erythema nodosum | Skin and subcutaneous tissue disorders | 1 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BMN 701 20 mg/kg |
|---|---|---|
| Hypoglycaemia | Metabolism and nutrition disorders | 16 of 24 |
| Headache | Nervous system disorders | 13 of 24 |
| Nausea | Gastrointestinal disorders | 8 of 24 |
| Dizziness | Nervous system disorders | 8 of 24 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 6 of 24 |
| Diarrhoea | Gastrointestinal disorders | 5 of 24 |
| Fatigue | General disorders | 5 of 24 |
| Fall | Injury, poisoning and procedural complications | 5 of 24 |
| Back pain | Musculoskeletal and connective tissue disorders | 5 of 24 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 5 of 24 |
Serious events with the highest arm-level rate: atrial fibrillation (4.2%), abdominal pain upper (4.2%), anaphylactic reaction (4.2%), fall (4.2%), blood creatine phosphokinase increased (4.2%).
The safety figures list 24 participants at risk for serious adverse events, with 10 affected. For other adverse events, 24 participants were at risk and 23 were affected. The record lists zero deaths. These figures describe participants recorded as having events; they do not by themselves establish that BMN 701 caused an event.
The record names six serious adverse-event terms, each with a reported percentage of 4.2%: atrial fibrillation, abdominal pain upper, anaphylactic reaction, fall, blood creatine phosphokinase increased, and hypoglycaemia. The entries do not state whether participants could contribute to more than one term, nor do they provide event counts, timing, duration, severity beyond the serious classification, or individual causal assessments. The listed percentages should be read as recorded, not combined or used to calculate a different summary.
Because this was a single-group study, the safety counts have no concurrent control group for comparison. They are descriptive counts within the treated study group, not comparative estimates of excess risk. The registry record does not report exposure-adjusted rates or detailed follow-up time for these figures. The zero deaths entry is the recorded count; it does not characterize other serious outcomes or establish a broader safety conclusion.
12. What the Result Does, and Does Not, Mean
The record establishes that a Phase 3, open-label, single-group switchover study was planned for participants with late-onset Pompe disease who had prior rhGAA exposure. It describes a direct switch to BMN 701 at 20 mg/kg by intravenous infusion every other week, with a 24-week initial period and an optional extension. It also identifies percent-predicted MIP at baseline and Week 24 as the primary outcome.
The registry record does not report numerical MIP results or the other listed efficacy outcome results. Consequently, the direction and size of the primary outcome change, its variability, and its precision are unknown from the registry information. No efficacy conclusion can be drawn from the outcome title or from the fact that the study was registered as Phase 3. The record also does not report the trial’s statistical analysis plan or sample-size justification.
The single-group, open-label design means that any within-group change would not be a randomized comparison against continued rhGAA or another control. It could describe measurements among participants who switched treatment, but it could not by itself attribute a change to BMN 701. The study population was limited to ambulatory participants with mild to moderate respiratory impairment and prior rhGAA exposure for 48 weeks or longer, so the design does not directly address other patient groups or treatment histories.
The safety entries describe affected-participant counts in the treated group and list zero deaths. They do not establish causation or comparative risk. The registry’s terminated status is recorded, but the reason is not reported in the registry record. Taken together, the registry information supports a description of the intended design and listed safety counts, not a determination of efficacy, comparative benefit, or a complete safety profile.
13. Why This Trial Matters Statistically
This trial is statistically notable as a switchover study in a population already receiving rhGAA. That design can document outcomes after a treatment transition in an experienced group, but its single-group structure sets clear limits on causal interpretation. There is no concurrent group continuing prior treatment, so a change between baseline and Week 24 would not, on its own, estimate the difference attributable to switching to BMN 701.
The primary measure is a continuous respiratory function outcome assessed at baseline and Week 24. A useful interpretation would require more than a visit-specific mean: readers would also need the amount of change, its variability or uncertainty, and the number of participants contributing data at each visit. Those numerical results are not reported in the registry record. The record therefore identifies the intended statistical question without allowing the magnitude or precision of its answer to be evaluated.
The study also highlights the distinction between a planned extension and documented follow-up. The regimen describes an optional extension after the initial treatment period, with a stated total therapy duration of 264 weeks, while the registry status is terminated. The reason for termination and the extent of follow-up are not reported in the registry record. The planned duration should not be mistaken for evidence that all participants completed that duration.
Finally, the registry lists several secondary outcomes and safety counts but does not report efficacy analyses. Without analysis methods, missing-data details, or a multiplicity approach, readers cannot determine how the outcomes were analyzed or how much confidence to place in any potential comparisons. The study remains useful for understanding the structure of a treatment-switch investigation, while its posted record leaves key result and interpretation questions unresolved.
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 primary limitation for statistical interpretation is the absence of numerical efficacy results in the registry record. Although MIP is identified as the primary endpoint and baseline and Week 24 are specified, the mean values, standard deviations, change estimate, confidence interval, and test results are not reported. The registry also lists zero analyses. The size, direction, and precision of the primary result therefore cannot be assessed.
The single-group, open-label design has no concurrent control. It cannot provide a randomized estimate comparing a switch to BMN 701 with continued rhGAA or another treatment. Because masking is listed as none, participants and investigators knew treatment assignment; the registry record does not describe safeguards for assessment or reporting that could address this feature.
The eligible population was restricted to ambulatory participants with mild to moderate respiratory impairment who had received rhGAA for 48 weeks or longer. The record does not provide further participant characteristics or enough information to determine how closely the enrolled group reflects other populations. Visit-specific analysis counts and missing-data methods are also not reported, so the effect of incomplete measurements cannot be evaluated.
The study is listed as terminated, but the reason is not reported in the registry record. The record does not establish whether the initial treatment period or optional extension was completed, or how long participants were followed for safety. The trial’s sample-size justification, statistical analysis plan, and approach to multiplicity are not reported. These gaps limit assessment of both the intended analyses and the completeness of the posted results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: BMN 701 Phase 3 in rhGAA Exposed Subjects With Late Onset Pompe Disease (INSPIRE Study) — NCT01924845.
- Registry record last updated 2018-06-14; status last verified 2018-06.
- Results first posted 2018-06-14.
- 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.
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18. Record Summary
NCT01924845 is a Phase 3, open-label, single-group switchover study sponsored by BioMarin Pharmaceutical. It enrolled 24 participants with late-onset Pompe disease who had prior rhGAA exposure. Participants were to receive BMN 701 20 mg/kg by intravenous infusion every other week for 24 weeks, with an optional extension.
The primary outcome was mean percent-predicted MIP at baseline and Week 24 in the full analysis set. The registry record lists secondary respiratory, walking, and non-serious adverse-event outcomes, but reports zero analyses and does not report numerical efficacy results. It lists 10 participants affected by serious adverse events, 23 affected by other adverse events, and zero deaths. The status is terminated; the reason is not reported in the registry record.