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 Late-Onset Treatment Study Extension Protocol (NCT00455195), a non-randomized phase 4 study. The primary outcome is Summary of Participants Reporting Treatment-Emergent Adverse Events For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00455195 |
| Phase | Phase 4 |
| Condition | Pompe Disease (Late-Onset), Glycogen Storage Disease Type II (GSD-II), Glycogenesis Type II |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 81 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Genzyme, a Sanofi Company |
| Results posted | Yes |
2. Clinical Question
Population
Participants with late-onset Pompe disease who had previously enrolled in the double-blind study AGLU02704. The registry describes the safety population as participants randomized to alglucosidase alfa in that study who received at least one infusion.
Intervention
Alglucosidase alfa in an open-label extension. The registry describes intravenous infusions of 20 mg/kg every other week. Participants who had received alglucosidase alfa in the earlier study continued treatment if they completed it; eligible participants who had received placebo entered the extension on alglucosidase alfa.
Comparator
There was no randomized comparator in the extension. The reported groups distinguish participants by their treatment history in the earlier study: alglucosidase alfa followed by alglucosidase alfa, and placebo followed by alglucosidase alfa.
Primary question
Among participants with prior exposure to alglucosidase alfa, how many reported treatment-emergent adverse events during the stated follow-up, including serious events, treatment-related events, and infusion-associated reactions? The posted results give counts for serious adverse events and other adverse events, but do not give counts for every category named in the endpoint description.
This is a safety-focused extension rather than a new randomized efficacy comparison. Its results describe reported events in participants who entered the extension after the earlier study, with treatment history defining the two reported groups. That design can describe the observed experience during follow-up, but it cannot by itself separate treatment effects from differences between the groups or from changes over time. The registry also lists secondary outcomes involving lower-limb muscle strength and physical quality of life, but their result values are not reported in the registry record.
3. Trial Design
The study is titled Late-Onset Treatment Study Extension Protocol and is described as an open-label extension for patients with late-onset Pompe disease previously enrolled in AGLU02704. It is a Phase 4 study with non-randomized allocation, no masking, and a parallel model. The recorded enrollment is 81. The study status is completed, with a start date of 2007-03 and primary completion of 2008-10.
Alglucosidase alfa is the intervention. The registry describes intravenous treatment at 20 mg/kg every other week. One reported group received alglucosidase alfa in the earlier double-blind study and continued it in the extension if they completed that study. The other group received placebo in the earlier study, completed it, and qualified to enter the extension on alglucosidase alfa. Both groups therefore received alglucosidase alfa during the extension, while their earlier treatment differed.
That treatment-history structure is important for interpretation. The extension itself was not randomized, and the groups are not a like-for-like control comparison. Any differences in reported outcomes between them could reflect their earlier treatment, other differences between participants, or other influences; the registry record does not provide an analysis that distinguishes these possibilities. The predecessor study is described as placebo-controlled and double-blind, but its design does not make the extension's treatment-history groups randomized within the extension.
The primary outcome concerns participants reporting treatment-emergent adverse events from Week 0 to 2.5 years, with the time frame stated from the start of AGLU02704. The registry also lists nine outcome measures overall, including secondary measures of lower-limb muscle strength and physical quality of life. Detailed protocol procedures, the rationale for the enrollment target, and the planned statistical analysis 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: 81 of the 90 participants enrolled in the double-blind placebo controlled AGLU02704 (NCT00158600) study continued on to the open-label extension study AGLU03206.
Double-blind Study AGLU02704
| Stage | Alglucosidase Alfa/Alglucosidase Alfa | Placebo/Alglucosidase Alfa |
|---|---|---|
| STARTED | 60 | 30 |
| COMPLETED | 55 | 26 |
| NOT COMPLETED | 5 | 4 |
Reasons for not completing this period:
| Reason | Alglucosidase Alfa/Alglucosidase Alfa | Placebo/Alglucosidase Alfa |
|---|---|---|
| Adverse Event | 2 | 1 |
| Death | 1 | 0 |
| Withdrawal by Subject | 2 | 2 |
| Unable to commit time to study | 0 | 1 |
Extension Study AGLU03206
| Stage | Alglucosidase Alfa/Alglucosidase Alfa | Placebo/Alglucosidase Alfa |
|---|---|---|
| STARTED | 55 | 26 |
| COMPLETED | 55 | 26 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The safety population includes all participants randomized to alglucosidase alfa treatment in AGLU02704 (NCT00158600) who received at least one infusion of alglucosidase alfa.
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 | Alglucosidase Alfa/Alglucosidase Alfa | Placebo/Alglucosidase Alfa | Total |
|---|---|---|---|---|
| Participants analysed | 60 | 26 | 86 | |
| Age, Continuous | years | 45.3 (SD 12.37) | 46.8 (SD 8.62) | 45.73 (SD 11.34) |
| Sex: Female, Male: Female | Participants | 26 | 15 | 41 |
| Sex: Female, Male: Male | Participants | 34 | 11 | 45 |
| Race/Ethnicity, Customized: Hispanic | participants | 1 | 1 | 2 |
| Race/Ethnicity, Customized: Asian | participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Black or African American | participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: White | participants | 57 | 24 | 81 |
| Race/Ethnicity, Customized: Unknown or Not Reported | participants | 1 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Summary of Participants Reporting Treatment-Emergent Adverse Events For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600), measured over Week 0 to 2.5 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint summarizes the number of participants reporting treatment-emergent adverse events during Week 0 to 2.5 years. The time frame is measured from the start of the earlier double-blind study, rather than being described solely as time from entry into the extension. Treatment-emergent adverse events are defined as events occurring after initiation of alglucosidase alfa treatment.
The endpoint description names adverse events, serious adverse events, treatment-related adverse events, and infusion-associated reactions. Counting participants who experienced an event is useful for describing how broadly events occurred across a safety population. It is different from counting the total number of event episodes: a participant with repeated events is still counted as a participant who experienced an event. The record gives affected-participant counts for serious adverse events and other adverse events. Counts for treatment-related events and infusion-associated reactions are not reported in the registry record.
Safety summaries of this kind describe observed events over a stated period; they do not establish that treatment caused an event. The endpoint is not an efficacy measure. The registry lists secondary efficacy-related measures, including muscle strength and physical quality of life, but their results are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety counts indicate that serious adverse events were reported for 15 of 60 participants in the Alglucosidase Alfa/Alglucosidase Alfa group, 2 of 26 in the Placebo/Alglucosidase Alfa group, and 17 of 86 overall. For other adverse events, the corresponding counts are 60 of 60, 25 of 26, and 85 of 86. These are descriptive counts within groups defined by treatment history, not estimates from a randomized comparison in the extension.
The record also lists selected serious-event terms with percentages: Cervix carcinoma stage II and Hydronephrosis at 3.8% each; Hypersensitivity and Fall at 3.3% each; and Coronary artery disease and Supraventricular tachycardia at 1.7% each. The registry does not explain the denominator for these term percentages in the information, so they should not be treated as participant-level risks without further detail. Nor does the listing establish that alglucosidase alfa caused any of these events.
The overall count denominators and the recorded enrollment do not match: the overall adverse-event group has 86 participants, while enrollment is recorded as 81. The registry record does not explain the relationship between those figures. The endpoint description also emphasizes participants with long-term alglucosidase alfa exposure, while reported groups include both treatment histories. This makes it important to retain the stated group labels and not assume that each figure refers to the same analysis population.
No inferential analyses, confidence intervals, or hypothesis-test results are reported in the registry record. The counts therefore describe observed reporting, but do not quantify the precision of a difference between groups. Because the extension was non-randomized and unmasked, comparisons by treatment history are especially vulnerable to differences in participant characteristics, follow-up, and event reporting. The posted results do not give enough information to adjust for such differences.
The record's endpoint description includes treatment-related adverse events and infusion-associated reactions, but their counts are absent from the reported results. Results for the listed muscle-strength and physical-quality-of-life outcomes are also not reported in the registry record. The available information supports a narrow reading: adverse-event counts were recorded over the stated period in the listed groups; broader conclusions about comparative safety or efficacy are not established by these counts alone.
9. Statistical Methods Explained
What does a participant count represent?
The primary outcome is expressed as the number of participants who experienced an event. This is a count of people, not a count of every event episode. A participant may experience more than one event, but the participant-level summary records that person as having experienced an event. This format is useful for showing how many people in the defined group had at least one event of the specified type.
The registry reports serious adverse-event counts and other adverse-event counts by treatment-history group. It does not provide event-level totals, person-time, or a detailed account of how repeated events were handled in the summary. Accordingly, the participant counts should not be read as rates per unit of follow-up or as measures of the number of event episodes.
Why do the denominators matter?
A count is most interpretable alongside the number of participants in the group being described. The serious-event figures are reported as 15 of 60, 2 of 26, and 17 of 86 overall; the other-event figures are reported as 60 of 60, 25 of 26, and 85 of 86 overall. These denominators identify the group sizes used in those summaries. They do not resolve the difference between the overall denominator of 86 and recorded enrollment of 81, which the registry record does not explain.
For a binary participant outcome, the observed count is subject to sampling variability: another group of similar participants might have a different count. General statistical practice often represents uncertainty with a confidence interval, which gives a range of values compatible with the data and an analysis method. No confidence intervals are reported for these results. Without them, the precision of the observed group summaries cannot be assessed from the registry results alone.
Why is this not a randomized comparison?
The extension is recorded as non-randomized and unmasked. Its groups are distinguished by earlier treatment: alglucosidase alfa followed by alglucosidase alfa, or placebo followed by alglucosidase alfa. The group labels therefore describe treatment history, not randomized assignment within the extension. A numerical difference between groups would be descriptive and could reflect pre-existing group differences as well as treatment history. The registry record provides no adjusted comparison that addresses those possibilities.
Masking can affect how participants and investigators recognize, report, or classify events. Because masking is recorded as none in this extension, the reported event counts should be interpreted as observations from an open-label setting. The registry does not report procedures for independent event adjudication or other steps that might address reporting or classification differences.
What analyses are reported?
The registry lists nine outcome measures and no analysis entries. It does not report hypothesis tests, p-values, adjusted effect estimates, or confidence intervals for the adverse-event counts. Those omissions mean that the posted results support description, not a formal statistical conclusion about a difference between the treatment-history groups. They also leave unclear whether any statistical comparisons were planned or conducted outside the registry results.
The sample-size material is a planning illustration based on an observed effect, not the original study's design justification and not observed power. Its stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it considers effects expressed as fractions of the observed effect. Such illustrations describe hypothetical future planning under their assumptions. They do not show the probability that this completed study detected an effect, and the registry record does not report the original sample-size justification.
How should the outcome categories be distinguished?
The endpoint description names adverse events, serious adverse events, treatment-related adverse events, and infusion-associated reactions. These categories are not interchangeable: seriousness concerns an event's classification, while treatment-relatedness concerns its assessed relationship to treatment, and an infusion-associated reaction identifies a particular event context. The record's definition of treatment-emergent events concerns timing after treatment initiation, not proof of causation. The reported counts cover serious adverse events and other adverse events; category-specific results for treatment-related events and infusion-associated reactions are not reported in the registry record.
The listed serious-event terms are accompanied by percentages, but the registry information does not explain their denominator or give uncertainty estimates for them. Percentages for event terms should therefore be read as registry-reported summaries, not as adjusted risks or evidence of causation. No additional calculations are needed to interpret the posted counts, and no statistical comparison can be reconstructed from them without assumptions and information not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists nine outcome measures, including the primary safety outcome and secondary measures of lower-limb muscle strength and physical quality of life. It does not report a multiplicity plan describing how the chance of false-positive findings across multiple outcomes would be handled. With several outcomes, statistical interpretation can depend on whether results were treated as confirmatory or exploratory and whether any adjustment was planned. Those details are not reported in the registry record.
No analysis entries are listed, and no inferential results are reported for the adverse-event summaries. The record does not give p-values, confidence intervals, model specifications, or a prespecified hierarchy of outcomes. The listed outcome measures alone do not establish which were primary for formal testing beyond the named primary safety endpoint.
Missing-data methods are not reported in the registry record. There is no description of how participants without complete follow-up, incomplete outcome assessments, or changes in exposure were handled. The reported safety population is described as including participants randomized to alglucosidase alfa in AGLU02704 who received at least one infusion; the results also show groups based on treatment history. The record does not explain all population transitions or how the reported denominators relate to recorded enrollment.
These gaps limit assessment of whether the observed counts represent all eligible participants and whether incomplete follow-up affected the summaries. They also prevent evaluation of any adjustment for multiple outcomes or missing observations. No imputation method, sensitivity analysis, or other missing-data analysis is reported in the registry record.
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 |
|---|---|---|---|
| Alglucosidase Alfa/Alglucosidase Alfa | 15 | 60 | 25.0% |
| Placebo/Alglucosidase Alfa | 2 | 26 | 7.7% |
| Overall | 17 | 86 | 19.8% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Alglucosidase Alfa/Alglucosidase Alfa | 60 of 60 |
| Placebo/Alglucosidase Alfa | 25 of 26 |
| Overall | 85 of 86 |
Most frequent serious adverse event terms
| Event term | Organ system | Alglucosidase Alfa/Alglucosidase Alfa | Placebo/Alglucosidase Alfa | Overall |
|---|---|---|---|---|
| Hypersensitivity | Immune system disorders | 2 of 60 | 0 of 26 | 2 of 86 |
| Fall | Injury, poisoning and procedural complications | 2 of 60 | 0 of 26 | 2 of 86 |
| Coronary artery disease | Cardiac disorders | 1 of 60 | 0 of 26 | 1 of 86 |
| Supraventricular tachycardia | Cardiac disorders | 1 of 60 | 0 of 26 | 1 of 86 |
| Abdominal pain | Gastrointestinal disorders | 1 of 60 | 0 of 26 | 1 of 86 |
| Gastric ulcer | Gastrointestinal disorders | 1 of 60 | 0 of 26 | 1 of 86 |
| Chest discomfort | General disorders | 1 of 60 | 0 of 26 | 1 of 86 |
| Non-cardiac chest pain | General disorders | 1 of 60 | 0 of 26 | 1 of 86 |
| Gastroenteritis | Infections and infestations | 1 of 60 | 0 of 26 | 1 of 86 |
| Pneumonia | Infections and infestations | 1 of 60 | 0 of 26 | 1 of 86 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Alglucosidase Alfa/Alglucosidase Alfa | Placebo/Alglucosidase Alfa | Overall |
|---|---|---|---|---|
| Fall | Injury, poisoning and procedural complications | 39 of 60 | 13 of 26 | 52 of 86 |
| Nasopharyngitis | Infections and infestations | 29 of 60 | 8 of 26 | 37 of 86 |
| Headache | Nervous system disorders | 31 of 60 | 6 of 26 | 37 of 86 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 25 of 60 | 4 of 26 | 29 of 86 |
| Hypoacusis | Ear and labyrinth disorders | 23 of 60 | 3 of 26 | 26 of 86 |
| Upper respiratory tract infection | Infections and infestations | 20 of 60 | 6 of 26 | 26 of 86 |
| Back pain | Musculoskeletal and connective tissue disorders | 19 of 60 | 6 of 26 | 25 of 86 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 23 of 60 | 2 of 26 | 25 of 86 |
| Diarrhoea | Gastrointestinal disorders | 20 of 60 | 2 of 26 | 22 of 86 |
| Muscle spasms | Musculoskeletal and connective tissue disorders | 17 of 60 | 5 of 26 | 22 of 86 |
Serious events with the highest arm-level rate: cervix carcinoma stage ii (3.8%), hydronephrosis (3.8%), hypersensitivity (3.3%), fall (3.3%), coronary artery disease (1.7%).
The serious adverse-event summaries report 15 of 60 participants in the Alglucosidase Alfa/Alglucosidase Alfa group, 2 of 26 in the Placebo/Alglucosidase Alfa group, and 17 of 86 overall. For other adverse events, the reported figures are 60 of 60, 25 of 26, and 85 of 86 overall. These are participant counts over the stated follow-up, which runs from Week 0 to 2.5 years measured from the start of the earlier study.
The group labels refer to treatment history, and the extension was non-randomized. The counts do not constitute a randomized comparison and should not be interpreted as proving that treatment caused or prevented events. The record reports selected serious-event terms with percentages, but does not explain their denominator. It also does not report counts for the treatment-related and infusion-associated-reaction categories named in the endpoint description.
Recorded enrollment is 81, while the overall adverse-event denominator is 86. The registry record does not explain this difference. No confidence intervals or inferential comparisons are reported, so the precision of the counts and any difference between groups cannot be assessed from the posted results.
12. What the Result Does, and Does Not, Mean
The results describe adverse events reported among participants grouped by treatment history during an open-label extension. They document that serious and other adverse events were counted, and give participant counts for those categories. They do not establish that alglucosidase alfa caused any specific event. Treatment-emergent means that an event occurred after treatment began; it does not, by itself, establish a causal relationship.
The reported groups do not form a randomized comparison within the extension. Both groups received alglucosidase alfa during the extension, while their earlier study treatment differed. Any contrast between their observed counts may reflect that history or other differences between participants, as well as any treatment-related effects. No adjusted analysis or inferential comparison is reported in the registry record.
The results also do not establish comparative efficacy. Although the registry lists secondary outcomes for muscle strength and physical quality of life, their result values are not reported in the registry record. The available safety summaries therefore cannot answer whether those outcomes changed or differed between groups.
Precision is another boundary on interpretation. The adverse-event figures are counts, without confidence intervals or hypothesis-test results. The selected serious-event terms carry percentages, but their denominator is not explained in the registry record. In addition, the recorded enrollment of 81 does not match the overall adverse-event denominator of 86, and the relationship is not explained.
The appropriate conclusion is limited to the posted descriptive information: the record reports participant counts for serious and other adverse events in the stated groups and period. It does not provide the design or analysis features needed for a causal comparison, nor does it report all categories named in the endpoint description or the listed secondary outcome results.
13. Why This Trial Matters Statistically
This study illustrates why an extension's treatment history and design must be kept distinct from the design of an earlier trial. The predecessor is described as placebo-controlled and double-blind, but this extension is non-randomized and unmasked. The extension groups represent prior treatment paths rather than an internally randomized treatment contrast. Treating them as equivalent to randomized arms would overstate what the design can support.
It also highlights the importance of stating the analysis population and denominator clearly. The registry describes a safety population based on participants randomized to alglucosidase alfa in the earlier study who received at least one infusion, reports two treatment-history groups, and gives an overall adverse-event denominator of 86 despite recorded enrollment of 81. The relationship among these figures is not explained in the registry record. Readers need that context to understand who contributes to each summary.
Finally, a count can be informative without being a comparative estimate. The serious and other adverse-event counts document observed participant experiences, but the absence of confidence intervals, hypothesis tests, and analysis details means that precision and comparative uncertainty are not quantified. The endpoint description names additional safety categories whose counts are not reported, while secondary outcome measures are listed without results. The record therefore offers a useful case in separating descriptive safety reporting from conclusions that require transparent analysis and fuller outcome reporting.
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 extension is open-label and non-randomized. Its groups are defined by earlier treatment history, so their observed adverse-event counts are not a like-for-like randomized comparison. Differences in participant characteristics or follow-up could influence the summaries, and no adjusted analysis is reported in the registry record.
The registry records enrollment of 81, while the overall adverse-event denominator is 86. It does not explain how those figures relate. The primary endpoint description focuses on long-term exposure in the alglucosidase alfa/alglucosidase alfa group, while adverse-event results are also reported for the placebo/alglucosidase alfa group. The record does not fully reconcile these population descriptions.
The posted safety results give counts for serious and other adverse events, but not for treatment-related adverse events or infusion-associated reactions, despite naming those categories in the endpoint description. The denominator for the percentages attached to selected serious-event terms is not explained. The record also gives no confidence intervals, hypothesis tests, or other inferential results.
Although secondary outcomes include muscle strength and physical quality of life, their results are not reported in the registry record. Missing-data procedures, outcome-assessment completeness, protocol-level analysis details, and the sample-size justification are also not reported in the registry record. These limitations restrict interpretation to the descriptive safety counts and prevent a fuller evaluation of efficacy, precision, or comparative effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Late-Onset Treatment Study Extension Protocol — NCT00455195.
- Registry record last updated 2014-03-07; status last verified 2014-02.
- Results first posted 2012-01-05.
- 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
NCT00455195 is a completed Phase 4, open-label extension study of participants with late-onset Pompe disease previously enrolled in AGLU02704. The study is recorded as non-randomized, unmasked, and parallel, with enrollment of 81. The intervention was alglucosidase alfa, described as intravenous treatment at 20 mg/kg every other week.
The primary outcome concerns treatment-emergent adverse events from Week 0 to 2.5 years, measured from the start of the earlier study. The posted results report serious and other adverse-event counts by treatment history and overall. They do not report inferential comparisons, confidence intervals, counts for every safety category named in the endpoint description, or results for the listed secondary outcomes. The registry record does not explain the difference between recorded enrollment and the overall adverse-event denominator.