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 A Study to Assess the Long-term Safety and Efficacy of ATB200/AT2221 in Adult Subjects With Late-Onset Pompe Disease (LOPD) (NCT04138277), a na phase 3 study. The primary outcome is Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04138277 |
| Phase | Phase 3 |
| Condition | Pompe Disease (Late-onset) |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 119 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Amicus Therapeutics |
| Results posted | Yes |
2. Clinical Question
Population
Adults with late-onset Pompe disease who completed Study ATB200-03 and then took at least one dose of the combination treatment in this extension study.
Intervention
ATB200, identified in the record as cipaglucosidase alfa, co-administered with an oral AT2221 capsule, identified as miglustat.
Comparator
There was no randomized control group. The record distinguishes a Treatment Continued Group and a Treatment Switched Group, but these are not like-for-like randomized comparison groups.
Primary question
What treatment-emergent adverse events, treatment-emergent serious adverse events, and adverse events leading to study-drug discontinuation were reported during the extension?
The study is described as a long-term, open-label extension for adults with late-onset Pompe disease who completed an earlier study. Its primary endpoint concerns safety: it counts participants experiencing treatment-emergent adverse events, serious treatment-emergent adverse events, and adverse events leading to discontinuation. The posted record also identifies changes in walking distance, lung function, muscle testing, patient-reported physical function and fatigue, mobility tasks, quality-of-life responses, and overall physical well-being as secondary outcomes.
The registry record identifies 119 participants as the enrollment and reports a mean of 40.5 months on treatment for the primary endpoint timeframe. The safety population is defined as participants who took at least one dose of the combination treatment in this extension. However, the record does not establish a treatment effect against an untreated or randomized control group. The two named groups reflect treatment continuation or switching, not a randomized comparison. The clinical question is therefore primarily descriptive: what safety events were recorded in this extension, and what follow-up outcomes were planned or reported?
3. Trial Design
This was a Phase 3, multicenter, international, open-label extension study. The registry describes a single-group model, with allocation listed as not applicable and masking as none. It enrolled adults with late-onset Pompe disease who had completed Study ATB200-03. The study is marked completed; its recorded start date is 2019-12-18 and its primary completion date is 2024-12-31.
Participants received ATB200 co-administered with AT2221. The record identifies ATB200 as cipaglucosidase alfa and AT2221 as miglustat. It also presents results by a Treatment Continued Group and a Treatment Switched Group. These labels do not change the design into a randomized controlled comparison: allocation is listed as not applicable, and the record explicitly cautions that the arms are not a like-for-like control comparison. Details of how participants came to be in each group are not reported in the registry record.
The primary endpoint timeframe is the entire extension study, with a mean of 40.5 months on treatment. This is a mean, not a statement that every participant had the same duration of follow-up. The registry defines the OLE Safety Population as all subjects who took at least one dose of ATB200/AT2221 in Study ATB200-07. The relationship between this safety population and every analysis population for the secondary outcomes is not reported in the registry record.
The registry lists 13 outcome measures, including the primary safety endpoint and secondary measures such as 6-Minute Walk Distance, sitting percent-predicted forced vital capacity, lower-extremity manual muscle testing, and patient-reported outcomes. No statistical analysis entries are reported in the registry record. Protocol details such as the planned analysis methods, handling of interim data, or the sample-size justification 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.
Pretreatment
| Stage | Treatment Continued Group | Treatment Switched Group |
|---|---|---|
| STARTED | 82 | 37 |
| COMPLETED | 81 | 37 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Treatment Continued Group | Treatment Switched Group |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
Treatment
| Stage | Treatment Continued Group | Treatment Switched Group |
|---|---|---|
| STARTED | 81 | 37 |
| COMPLETED | 58 | 30 |
| NOT COMPLETED | 23 | 7 |
Reasons for not completing this period:
| Reason | Treatment Continued Group | Treatment Switched Group |
|---|---|---|
| Adverse Event | 6 | 2 |
| Lost to Follow-up | 1 | 0 |
| Pregnancy | 3 | 0 |
| COVID-19 pandemic | 1 | 0 |
| Withdrawal by Subject | 9 | 3 |
| Sponsor decision | 1 | 0 |
| Physician Decision | 1 | 0 |
| Worsening of condition | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: Open-label extension (OLE) Safety Population defined as all subjects who took at least one dose of ATB200/AT2221 combination treatment in Study ATB200-07
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 | Treatment Continued Group | Treatment Switched Group | Total |
|---|---|---|---|---|
| Participants analysed | 81 | 37 | 118 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 69 | 34 | 103 |
| Age, Categorical: >=65 years | Participants | 12 | 3 | 15 |
| Age, Continuous | years | 48.9 (SD 13.53) | 46.0 (SD 13.47) | 48.0 (SD 13.52) |
| Sex: Female, Male: Female | Participants | 48 | 18 | 66 |
| Sex: Female, Male: Male | Participants | 33 | 19 | 52 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 5 | 5 | 10 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 71 | 30 | 101 |
| Race (NIH/OMB): More than one race | Participants | 5 | 1 | 6 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Enzyme Replacement Therapy (ERT)-experienced | Participants | 61 | 29 | 90 |
| ERT-naive | Participants | 20 | 8 | 28 |
| Age at diagnosis | years | 40.3 (SD 13.82) | 37.2 (SD 15.40) | 39.3 (SD 14.35) |
6. Primary Endpoint
The registry lists the primary outcome as Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug, measured over Entire extension study (mean = 40.5 months on treatment).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants who experienced treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and TEAEs leading to discontinuation of study drug. Its timeframe is the entire extension study, reported as a mean of 40.5 months on treatment. The endpoint is intended to summarize the occurrence of safety events during exposure to the study treatment; it is not a measure of treatment benefit.
Counting participants is a straightforward way to describe how many people in a defined safety population experienced an event category. The count depends on the population and follow-up being considered. In an extension study, participants may have different exposure and observation times, so a count alone does not describe the timing or duration of events. General statistical context: event counts and participant counts answer different questions. A participant who experiences more than one event may still contribute only once to a count of participants with that event category, depending on the endpoint definition.
The registry record gives the endpoint definition and safety population, but the posted information does not provide a complete set of primary-endpoint counts, including the number with TEAEs leading to discontinuation. It reports serious-event and other-event figures by group, which should be read as the listed categories rather than as a complete substitute for every component of the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety figures are descriptive. In the Treatment Continued Group, 17 of 81 participants are listed as having a serious adverse event; in the Treatment Switched Group, the corresponding figures are 10 of 37. The record also lists other adverse events for 80 of 81 participants in the Treatment Continued Group and 37 of 37 in the Treatment Switched Group. Deaths are listed as 1 and 0, respectively. These are participant counts within the displayed groups, not estimates from a randomized comparison.
The group labels should not be treated as intervention and control arms. The registry identifies an open-label extension, gives allocation as not applicable, and states that the arms are not a like-for-like control comparison. Differences in the displayed counts therefore cannot, by themselves, establish that treatment continuation or switching caused a difference in event occurrence. The record does not report the reasons for group assignment or enough information to adjust for possible differences between groups.
The serious adverse event terms listed most frequently in the record are Arrhythmia, Intestinal perforation, Pancreatitis, Chest pain, Bile duct stone, and Cholecystitis acute, each shown as 2.7%. The registry record does not provide event counts alongside those percentages in this information, nor does it give enough detail to assess whether any listed event was considered related to treatment. These terms describe reported events; they do not establish causation.
Although the primary endpoint also includes TEAEs leading to discontinuation, a corresponding participant count is not stated in the posted results. The registry record also does not provide a complete numerical account of every component of the primary endpoint. Likewise, the outcome list identifies several planned or registered measures of walking, respiratory function, muscle strength, and patient-reported experience, but their numerical results are not reported in the registry record. No efficacy conclusion can be drawn from the endpoint names alone.
The mean treatment timeframe of 40.5 months indicates extended observation on average, but it does not show how long each individual participant was followed. Nor does it convert the displayed counts into event rates over a common time interval. General statistical context: interpretation of safety counts depends on the number of people observed, their exposure time, event definitions, and completeness of follow-up. The record’s group-level counts are useful descriptive information, but they do not answer a comparative causal question.
9. Statistical Methods Explained
The registry record describes a Phase 3 open-label extension and lists a single-group model. Allocation is marked not applicable and masking is listed as none. Those design features matter when interpreting the posted results: treatment and outcomes were not described as being compared under randomized allocation or blinded assessment. The record separately displays two groups, but explicitly cautions against treating them as like-for-like controls.
What a participant count represents
The primary outcome is expressed as a count of participants with specified safety events. A count is an absolute description of how many people in the defined population experienced an event category. The safety population is defined as participants who took at least one dose of the combination treatment in Study ATB200-07. When reading a count, the relevant denominator is the number of participants at risk in the corresponding group, as displayed with the adverse-event figures.
General statistical context: a participant count is not the same as a count of all event episodes. If a person has repeated events, a participant-based measure may count that person once for a given category, while an event-based measure may count multiple episodes. The record describes the primary endpoint as the number of subjects with the event categories, but details of event-level counting rules are not reported in the registry record.
Why group counts are not a treatment comparison
In a randomized comparison, random allocation is used to make groups comparable in expectation. Here, allocation is listed as not applicable, and the record identifies the study as an open-label extension. The continued and switched groups are therefore descriptive groupings rather than a randomized treatment contrast. General statistical context: when groups may differ in their characteristics or treatment histories, observed differences can reflect those differences, follow-up, or other factors as well as treatment. A simple contrast between the displayed counts would not resolve those possibilities.
No comparative effect estimate, confidence interval, or p-value is reported in the registry record. A confidence interval, in general, describes uncertainty around an estimated quantity under a specified statistical model. Without a reported estimate and interval, the precision of a comparative effect cannot be assessed from these safety counts alone. The registry record lists zero analysis entries, so a formal inferential analysis is not available in the posted record.
Follow-up and event frequency
The primary endpoint covers the entire extension study and reports a mean of 40.5 months on treatment. This gives context for the observation period but does not show the distribution of individual follow-up times. General statistical context: when participants contribute different amounts of observation time, a count of people with an event does not by itself account for those differences. Time-to-event analyses or rates may address different questions, but the registry record does not report such analyses. The recorded endpoint is a count of participants, not a time-to-event estimate.
The serious adverse event summary lists selected terms with percentages, including six terms each shown as 2.7%. Those entries should be interpreted as the registry’s reported summaries. The record does not provide enough detail to reconstruct the event-term denominators or determine whether the percentages use a shared denominator. No additional arithmetic or re-expression is needed to read the percentages as posted.
Planning illustrations and observed evidence
The accompanying sample-size section is described as a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It is not the study’s own design justification and is not observed power. General statistical context: a planning calculation describes the sample size that might be needed under stated assumptions; it does not show the probability that a completed study has detected a true effect. These illustrations should not be confused with the extension’s observed enrollment or with a randomized comparison, particularly because this registry record describes a single-group open-label extension and supplies no analysis entries.
The record does not report the statistical methods used for the secondary outcome measures, adjustment for baseline values, analysis of repeated measurements, or confidence intervals for changes. Those choices can affect estimates and their uncertainty. In their absence, the outcome titles alone do not establish how results were analyzed or how precisely any changes were estimated.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures. The secondary outcomes named in the record span walking distance, sitting percent-predicted forced vital capacity, lower-extremity manual muscle testing, physical function and fatigue questionnaires, a gait and mobility test, EQ-5D-5L responses, and a global impression of change. Considering many outcomes raises a general statistical issue: if multiple tests are conducted, the chance of at least one apparently unusual result can increase. The registry record does not report whether or how multiplicity was addressed.
Missing-data methods are not reported in the registry record. In particular, the record does not state how missing visits or incomplete questionnaire and performance-test measurements were handled, whether participants with incomplete follow-up were included in each secondary analysis, or whether any imputation method was used. These details matter because the observed participants and time points may not represent everyone enrolled equally.
The stated OLE Safety Population includes all participants who took at least one dose of ATB200/AT2221 in Study ATB200-07. The registry record does not report whether this same population was used for all efficacy outcomes, nor does it give a separate analysis population definition for each measure. It also does not describe how treatment discontinuation or withdrawal affected follow-up analyses.
The record lists zero analysis entries. Consequently, statistical analysis plans, multiplicity procedures, missing-data assumptions, and analysis populations beyond the stated safety population are not reported in the registry record. This limits assessment of how complete and comparable the outcome data were, and how uncertainty around the results should be interpreted.
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 |
|---|---|---|---|
| Treatment Continued Group | 17 | 81 | 21.0% |
| Treatment Switched Group | 10 | 37 | 27.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment Continued Group | 1 of 81 |
| Treatment Switched Group | 0 of 37 |
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 |
|---|---|
| Treatment Continued Group | 80 of 81 |
| Treatment Switched Group | 37 of 37 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment Continued Group | Treatment Switched Group |
|---|---|---|---|
| COVID-19 pneumonia | Infections and infestations | 1 of 81 | 1 of 37 |
| Pneumonia | Infections and infestations | 1 of 81 | 1 of 37 |
| Tibia fracture | Injury, poisoning and procedural complications | 2 of 81 | 0 of 37 |
| Anemia | Blood and lymphatic system disorders | 1 of 81 | 0 of 37 |
| Acute myocardial infarction | Cardiac disorders | 1 of 81 | 0 of 37 |
| Conduction disorder | Cardiac disorders | 1 of 81 | 0 of 37 |
| Arrhythmia | Cardiac disorders | 0 of 81 | 1 of 37 |
| Conjunctival hemorrhage | Eye disorders | 1 of 81 | 0 of 37 |
| Intestinal perforation | Gastrointestinal disorders | 0 of 81 | 1 of 37 |
| Pancreatitis | Gastrointestinal disorders | 0 of 81 | 1 of 37 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment Continued Group | Treatment Switched Group |
|---|---|---|---|
| COVID-19 | Infections and infestations | 43 of 81 | 21 of 37 |
| Fall | Injury, poisoning and procedural complications | 39 of 81 | 18 of 37 |
| Headache | Nervous system disorders | 28 of 81 | 14 of 37 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 26 of 81 | 11 of 37 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 17 of 81 | 13 of 37 |
| Diarrhea | Gastrointestinal disorders | 21 of 81 | 7 of 37 |
| Back pain | Musculoskeletal and connective tissue disorders | 20 of 81 | 7 of 37 |
| Myalgia | Musculoskeletal and connective tissue disorders | 18 of 81 | 9 of 37 |
| Nasopharyngitis | Infections and infestations | 19 of 81 | 5 of 37 |
| Fatigue | General disorders | 13 of 81 | 8 of 37 |
Serious events with the highest arm-level rate: arrhythmia (2.7%), intestinal perforation (2.7%), pancreatitis (2.7%), chest pain (2.7%), bile duct stone (2.7%).
The registry displays serious adverse events, other adverse events, and deaths separately for the Treatment Continued Group and the Treatment Switched Group. For serious events, it lists 17 affected participants among 81 at risk in the continued group and 10 among 37 at risk in the switched group. For other adverse events, it lists 80 among 81 and 37 among 37, respectively. Deaths are listed as 1 in the continued group and 0 in the switched group.
These are descriptive counts from an open-label extension, not results from randomized control arms. The record cautions that the groups are not a like-for-like control comparison. The serious-event terms listed are Arrhythmia, Intestinal perforation, Pancreatitis, Chest pain, Bile duct stone, and Cholecystitis acute, each reported as 2.7%. The record does not establish that these events were caused by treatment, and the posted summary does not give the participant count for TEAEs leading to discontinuation. Read the group figures as safety reporting in the registry, not as proof of relative risk or treatment effect.
12. What the Result Does, and Does Not, Mean
This record contributes descriptive information about adverse events observed during an open-label extension of ATB200 co-administered with AT2221 in adults with late-onset Pompe disease who completed Study ATB200-03. The registry reports group-level counts for serious and other adverse events and deaths, and lists several serious-event terms with percentages. It also identifies a range of secondary functional and patient-reported outcomes.
The information does not establish whether the treatment caused any particular event. Nor does it establish whether the combination is more or less safe or effective than an alternative, because the study is not described as a randomized comparison and the registry warns that the displayed groups are not like-for-like controls. The posted record does not include numerical results for the listed secondary outcomes or a complete numerical account of every component of the primary endpoint.
The study’s extension design also means that participants had completed an earlier study before entering this study. The findings therefore describe this extension population, rather than all adults with late-onset Pompe disease. The safety population includes participants who took at least one dose in the extension; the registry record does not explain how people who did not enter, discontinued, or had incomplete outcome data were represented in other analyses.
General statistical context: descriptive safety counts can help characterize what was recorded during follow-up, but interpretation requires attention to event definitions, observation time, population selection, and missing information. The mean of 40.5 months on treatment gives an average timeframe, not a uniform duration for all participants. The counts and percentages should therefore be read as the posted summaries, without turning them into causal or comparative conclusions.
13. Why This Trial Matters Statistically
Long-term extension studies address a different statistical question from short-term randomized comparisons. They can describe treatment exposure and safety events over an extended period among people who continue into follow-up. This study’s primary endpoint is framed around treatment-emergent adverse events, serious adverse events, and events leading to discontinuation, with a mean of 40.5 months on treatment reported for the timeframe.
That information can be useful for understanding which events were recorded in the extension population and what follow-up was undertaken. The record also registers a broad set of functional and patient-reported outcomes, including walking, respiratory function, muscle testing, physical function, fatigue, mobility tasks, quality-of-life responses, and overall physical well-being. These measures indicate the kinds of outcomes the study sought to track beyond safety.
The statistical importance of the design is equally clear: an open-label extension with allocation marked not applicable does not supply a randomized control comparison. The continued and switched groups should not be read as if they were randomized arms. The registry record lists no analysis entries, so it does not provide inferential results or methods that would quantify comparative effects and their uncertainty.
The study therefore matters as a source of long-term descriptive safety reporting and as a record of outcomes assessed in a specific extension population. Its value should be understood alongside its limits: results from an extension can characterize observed follow-up, but the posted record does not establish causal treatment effects or resolve comparisons with other care.
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 study is open-label, with masking listed as none and allocation listed as not applicable. The registry identifies a single-group model and warns that the Treatment Continued Group and Treatment Switched Group are not a like-for-like control comparison. This precludes interpreting the displayed group counts as randomized evidence that one treatment history caused more or fewer events.
Participants were adults with late-onset Pompe disease who completed Study ATB200-03. That entry requirement defines a selected extension population; the findings do not automatically describe people who did not complete the earlier study or did not enter this extension. Details of the group assignment process and the treatment histories represented by the continued and switched labels are not reported in the registry record.
The primary endpoint timeframe is the entire extension study, with a mean of 40.5 months on treatment. Individual follow-up durations and the distribution of exposure are not reported in the registry record. The displayed event counts therefore do not, on their own, account for differences in time under observation. The record also does not provide a complete numerical account of the primary endpoint, including the count for adverse events leading to study-drug discontinuation.
Although 13 outcome measures are listed, numerical results for the secondary outcomes are not reported in the registry record. The record lists zero analysis entries and does not describe methods for missing data, multiplicity, or analysis populations beyond the stated safety population. Statistical plans, sample-size justification, interim analyses, and further details of the event definitions are not reported in the registry record. These gaps limit assessment of precision, completeness, and the robustness of any interpretation beyond the descriptive summaries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Assess the Long-term Safety and Efficacy of ATB200/AT2221 in Adult Subjects With Late-Onset Pompe Disease (LOPD) — NCT04138277.
- Registry record last updated 2026-03-05; status last verified 2026-03.
- Results first posted 2026-01-12.
- 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
This completed Phase 3 study was an open-label extension of ATB200 co-administered with AT2221 in adults with late-onset Pompe disease who completed Study ATB200-03. The registry records enrollment of 119 and a mean of 40.5 months on treatment for the primary endpoint timeframe. The safety population includes participants who took at least one dose of the combination in Study ATB200-07.
The primary endpoint counts participants with treatment-emergent adverse events, serious treatment-emergent adverse events, and events leading to study-drug discontinuation. Posted safety figures are displayed for Treatment Continued and Treatment Switched groups, but the registry cautions that these are not like-for-like control groups. The registry lists 13 outcome measures, but no analysis entries are reported. Numerical secondary-outcome results, several analysis details, and a complete account of all primary-endpoint components are not reported in the registry record.