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 Evaluate the Safety of Aceneuramic Acid Extended Release (Ace-ER; UX001) Tablets in Glucosamine (UDP-N-acetyl)-2-Epimerase (GNE) Myopathy (GNEM) (Also Known as Hereditary Inclusion Body Myopathy [HIBM]) Patients With Severe Ambulatory Impairment (NCT02731690), a na phase 2 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02731690 |
| Phase | Phase 2 |
| Condition | Hereditary Inclusion Body Myopathy, Distal Myopathy With Rimmed Vacuoles, Distal Myopathy, Nonaka Type |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 42 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ultragenyx Pharmaceutical Inc |
| Results posted | Yes |
2. Clinical Question
The central question is whether treatment-emergent adverse events, serious treatment-emergent adverse events, and adverse events leading to discontinuation were observed during open-label treatment with aceneuramic acid extended-release (Ace-ER) in participants with GNE myopathy and severe ambulatory impairment. The registry describes the primary objective as evaluating the safety of 6 g/day Ace-ER.
Population
Participants with GNE myopathy, also known as hereditary inclusion body myopathy, and severe ambulatory impairment. The primary analysis population is the Safety Analysis Set: enrolled participants who received at least 1 dose of study drug.
Intervention
Open-label aceneuramic acid extended-release tablets, referred to as Ace-ER, at 6 g/day.
Comparator
There was no comparison group. This was a single-group study, so the safety counts do not represent a randomized comparison with placebo or another treatment.
Primary question
How many participants had treatment-emergent adverse events, serious treatment-emergent adverse events, or treatment-emergent adverse events leading to discontinuation during the stated safety observation period?
The primary endpoint is a safety outcome, not a measure of functional benefit. The registry also lists functional measures, including mobility, upper-extremity, and self-care domains of the GNEM-FAS Expanded Version, as secondary outcomes. Their numerical results are not reported in the registry record summarized for this analysis. Consequently, the question addressed by the posted primary results is limited to adverse-event counts. Without a control group, observed events cannot be contrasted with what might have occurred in a comparable untreated group.
3. Trial Design
This was a Phase 2, open-label, single-group study sponsored by Ultragenyx Pharmaceutical Inc. The registry lists 42 participants as enrolled. The intervention was Ace-ER at 6 g/day. The study began on 2016-04-29, had a primary completion date of 2018-01-10, and is listed as terminated.
Open-label means that treatment was not masked. The registry lists masking as none and allocation as not applicable. Since participants were not assigned across multiple arms, the design does not provide a concurrent control group. The adverse-event counts therefore describe events among participants receiving the study drug; they do not estimate a treatment-versus-control contrast.
The primary safety observation period was 48 Weeks, with an additional 30 [+5] days for participants not enrolling in the extension study. The endpoint description defines a treatment-emergent adverse event as an adverse event occurring after the first dose of study drug. The safety population is defined as all enrolled participants who received at least 1 dose. The adverse-event summary lists 42 participants at risk for both serious and other adverse events.
The registry lists safety assessments including clinically significant changes from baseline in physical examinations, vital signs, and clinical laboratory results, as well as suicidal behaviors and/or ideation. It also lists changes in GNEM-FAS Expanded Version mobility, upper-extremity, and self-care scores. These are secondary outcomes, not the primary safety endpoint. Numerical results for these outcomes are not reported in the registry record summarized for this analysis. Details of the rationale for the enrollment target, the conduct of interim analyses, and a fuller statistical analysis plan 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.
Overall Study
| Stage | UX001 6g/Day |
|---|---|
| STARTED | 42 |
| COMPLETED | 12 |
| NOT COMPLETED | 30 |
Reasons for not completing this period:
| Reason | UX001 6g/Day |
|---|---|
| Adverse Event | 1 |
| Withdrawal by Subject | 3 |
| Discontinuation of Study by Sponsor | 26 |
Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
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 | UX001 6g/Day |
|---|---|---|
| Participants analysed | 42 | |
| Age, Continuous | years | 46.0 (SD 13.97) |
| Sex: Female, Male: Female | Participants | 25 |
| Sex: Female, Male: Male | Participants | 17 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 42 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race/Ethnicity, Customized: White | Participants | 31 |
| Race/Ethnicity, Customized: Asian | Participants | 2 |
| Race/Ethnicity, Customized: Other (Not Specified) | Participants | 9 |
| Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy Functional Activities Scale(GNEM-FAS) Mobility Score | units on a scale | 10.63 (SD 7.816) |
| GNEM-FAS Upper Extremity Domain Score | units on a scale | 15.20 (SD 8.897) |
| GNEM-FAS Self-Care Domain Score | units on a scale | 13.00 (SD 7.413) |
| GNEM-FAS Total Score | units on a scale | 38.83 (SD 23.116) |
| Hand-Held Dynamometry (HHD) Raw Strength: Average Grip | kgf | 5.535 (SD 7.6778) |
| HHD Raw Strength: Average Shoulder Abduction | kgf | 3.880 (SD 4.4583) |
| HHD Raw Strength: Average Wrist Extension | kgf | 3.532 (SD 3.5177) |
| HHD Lower Extremity Muscle Strength: Average Knee Extension | kgf | 10.50 (SD 8.001) |
| HHD Raw Strength: Key Pinch | kgf | 1.790 (SD 2.1614) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation, measured over 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to discontinuation. A TEAE is defined in the registry as an adverse event occurring after the first dose of study drug. An adverse event is an untoward medical occurrence associated with use of a drug, whether or not it is considered drug-related. The registry definition of a serious event includes outcomes such as death, a life-threatening event, inpatient hospitalization or prolongation of hospitalization, persistent or significant incapacity or disability, or congenital anomaly or birth defect.
Counting participants with events is a straightforward way to describe how many people experienced an event during the observation period. The separate serious-event count distinguishes events meeting the registry’s seriousness criteria from other events. The discontinuation component captures events that led participants to stop treatment, although its numerical result is not reported in the registry record.
These counts are relevant to safety monitoring, but they do not by themselves establish that study drug caused an event. The definition explicitly includes events whether or not considered drug-related. Nor do participant counts describe the full pattern of event timing, duration, recurrence, or severity beyond the serious-event classification. Such details are not reported in the registry record summarized for this analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results list 1 participant with a serious treatment-emergent adverse event among 42 participants at risk, and 26 participants with other treatment-emergent adverse events among 42 at risk. The record lists 0 deaths. These figures describe participants, rather than the total number of event occurrences: one participant may experience more than one event, and the counts alone do not show how events were distributed over time.
The serious-event terms listed most often are pyelonephritis, sepsis, and nephrolithiasis, each reported as 2.4%. These are the registry’s stated percentages. The record does not give the event counts for each term in the registry record, nor does it clarify whether the listed terms occurred in distinct participants or whether a participant could contribute more than one term. The percentages should therefore be read as reported, without treating them as a complete accounting of all event types.
The primary endpoint title also includes TEAEs leading to discontinuation, but a corresponding participant count is not reported in the registry record. The available count of 26 for other TEAEs should not be taken as the count who discontinued treatment. Similarly, the serious-event count is not a count of all adverse events, and the 0 deaths entry refers only to deaths listed in the adverse-event summary.
Because this was an open-label, single-group study, the counts are descriptive. There is no randomized comparator for estimating whether the occurrence of events differed from an alternative treatment or from no study treatment. The numbers also do not establish whether an event was caused by Ace-ER: the registry definition includes events regardless of whether they were considered drug-related.
Precision cannot be fully assessed from the participant counts alone. No confidence intervals for the safety estimates are reported in the registry record. General statistical context: a confidence interval expresses uncertainty around an estimate; without one, readers should avoid treating a count from a limited study population as a precise estimate of event frequency in a broader population. The record’s enrollment of 42 and event counts describe this study, not all people with GNE myopathy.
The registry lists functional outcomes as secondary measures, but their numerical results are not reported in the registry record. Accordingly, these safety results do not answer whether mobility, upper-extremity function, or self-care changed. The interpretation should remain confined to the adverse-event observations and the limitations of an uncontrolled safety study.
9. Statistical Methods Explained
The primary outcome is binary at the participant level: a participant either had a specified category of event during the observation period or did not. The registry reports counts of participants, which is why the natural description is a number of people with an event rather than a mean score. The listed safety population includes enrolled participants who received at least 1 dose of study drug.
What participant counts convey
A participant count answers how many people in the safety population met an endpoint definition. Here, the record lists 1 participant with a serious TEAE and 26 with other TEAEs, with 42 participants at risk for each category. These categories describe people, not necessarily unique event episodes. A participant can have multiple adverse events, and the count of participants does not reveal the total number of event reports or the number of repeated events per person.
General statistical context: binary outcomes can also be described as proportions, but translating counts into percentages requires a calculation. The posted account states event percentages for selected serious terms, so those figures can be quoted as recorded. No additional percentages or confidence limits are inferred from the participant counts in this explanation.
Why study design matters
Allocation is listed as not applicable, masking as none, and the model as single group. Thus, this is a descriptive safety assessment rather than a randomized comparison. In a randomized comparison, differences between groups can help distinguish treatment-associated patterns from background event occurrence, subject to the trial’s design and analysis. This study has no such comparator, so an event count cannot establish what would have happened to the same participants under a different treatment or without study treatment.
Open-label conduct means that treatment was not masked. General statistical context: lack of masking can affect event recognition, reporting, or attribution, particularly for outcomes that involve judgment. The registry’s adverse-event definition includes events regardless of whether they were considered drug-related, which reinforces the distinction between an event occurring after treatment begins and proof that treatment caused it.
Observation window and endpoint definitions
The listed timeframe is 48 Weeks, plus 30 [+5] days for participants not enrolling in the extension study. The registry defines TEAEs as events occurring after the first dose. This makes the endpoint a treatment-emergent measure over the stated follow-up, not a comparison of event status before and after treatment. The serious-event criteria include death, a life-threatening event, inpatient hospitalization or prolongation of hospitalization, persistent or significant incapacity or disability, and congenital anomaly or birth defect.
Time at risk can matter when participants have different follow-up durations. General statistical context: a simple participant count does not adjust for different lengths of observation or quantify event rates per unit of time. The record gives the endpoint timeframe, but the detailed participant-level follow-up distribution and time-to-event analysis are not reported in the registry record.
Precision and uncertainty
General statistical context: a point estimate summarizes the observed data, while a confidence interval gives a range of values compatible with the data under a statistical model. For event counts, uncertainty is often important because a small study can produce an estimate that varies substantially across samples. The registry record does not report confidence intervals for the primary safety counts, so the reported counts should be treated as descriptive rather than as highly precise estimates of underlying event occurrence.
Rare or serious events may be particularly difficult to characterize in a study of this size. A count of 1 serious-event participant establishes that such an event was recorded in the study population; it does not establish the probability of that event for all potential patients or under other circumstances. Likewise, 0 deaths in this record means no deaths are listed in this adverse-event summary; it does not establish that the risk of death is absent.
Planning illustrations are not trial design evidence
The registry-associated sample-size illustrations are described as planning calculations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These illustrations are not the study’s original design justification. They describe hypothetical planning under a two-arm framework, whereas the actual study was single-group. The registry does not report the study’s sample-size justification, so the illustrations should not be read as evidence that the trial was designed or powered for a particular comparison.
General statistical context: power is a design property tied to a specified effect, outcome, analysis, and assumptions. Calculations based on an observed effect are retrospective planning illustrations and do not demonstrate that the completed study had a particular observed power. No power claim for the actual study follows from the safety counts alone.
Multiplicity and statistical analysis details
The registry lists 15 outcome measures and 32 analyses. Multiple outcomes or analyses can raise the question of how statistical error is controlled when many hypotheses are tested. The registry record does not report a multiplicity adjustment or enough detail to determine how the analyses were prioritized. It also does not report the specific statistical methods used for every listed outcome. Therefore, no unreported adjustment or model should be presumed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 15 outcome measures and 32 analyses. This indicates that the record includes multiple assessments, spanning safety and functional domains. When many outcomes or analyses are considered, general statistical context is that the chance of at least one apparently unusual result can increase if each is interpreted as a separate test. Methods such as prespecifying a primary outcome or adjusting for multiple testing can address aspects of this issue, but the registry record does not report whether a multiplicity procedure was used. The primary endpoint is identified, but details of any hierarchy or adjustment are not reported.
Missing-data handling is also not reported in the registry record. The listed Safety Analysis Set includes enrolled participants who received at least 1 dose, but this population definition does not specify how missing visits, incomplete follow-up, or unavailable endpoint information were treated. The timeframe allows for an extension-related follow-up distinction, but the record does not provide the distribution of follow-up or explain how participants with differing observation periods contributed to each endpoint.
For the primary safety outcome, 42 participants are listed at risk for serious and other adverse events. The registry record does not describe whether all participants had complete observation across the full timeframe. It also does not report a missing-data sensitivity analysis. Without those details, the participant counts should be interpreted as the posted safety summary, not as evidence that every participant had identical follow-up or complete data for every listed outcome.
The registry identifies the safety population, but analysis populations for the secondary outcomes and the handling of missing functional measurements are not reported in the registry record. This limits interpretation of the broader set of planned assessments beyond the primary safety counts.
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 |
|---|---|---|---|
| Ace-ER 6 g/Day | 1 | 42 | 2.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Ace-ER 6 g/Day | 0 of 42 |
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 |
|---|---|
| Ace-ER 6 g/Day | 26 of 42 |
Most frequent serious adverse event terms
| Event term | Organ system | Ace-ER 6 g/Day |
|---|---|---|
| Pyelonephritis | Infections and infestations | 1 of 42 |
| Sepsis | Infections and infestations | 1 of 42 |
| Nephrolithiasis | Renal and urinary disorders | 1 of 42 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ace-ER 6 g/Day |
|---|---|---|
| Abdominal distension | Gastrointestinal disorders | 7 of 42 |
| Flatulence | Gastrointestinal disorders | 7 of 42 |
| Upper respiratory tract infection | Infections and infestations | 7 of 42 |
| Abdominal pain upper | Gastrointestinal disorders | 6 of 42 |
| Fall | Injury, poisoning and procedural complications | 4 of 42 |
| Muscular weakness | Musculoskeletal and connective tissue disorders | 4 of 42 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 4 of 42 |
| Dyspepsia | Gastrointestinal disorders | 3 of 42 |
| Dysphagia | Gastrointestinal disorders | 3 of 42 |
| Nausea | Gastrointestinal disorders | 3 of 42 |
Serious events with the highest arm-level rate: pyelonephritis (2.4%), sepsis (2.4%), nephrolithiasis (2.4%).
The safety summary lists 1 participant with a serious TEAE among 42 at risk, 26 participants with other TEAEs among 42 at risk, and 0 deaths. These are participant counts, not necessarily counts of unique event episodes. The registry lists pyelonephritis, sepsis, and nephrolithiasis among the top serious-event terms, each at 2.4%. Those percentages are reproduced as recorded and should not be combined or interpreted as a count of distinct participants.
Seriousness is defined by regulatory-style outcomes such as death, a life-threatening event, hospitalization or its prolongation, persistent or significant incapacity or disability, or congenital anomaly or birth defect. Seriousness is not the same as severity. The registry’s definition of an adverse event also does not require that the event be considered drug-related. Accordingly, these figures indicate events recorded during the treatment-emergent period, not proof of causation.
The endpoint includes events leading to discontinuation, but the corresponding number is not reported in the registry record. The count of 26 for other TEAEs should not be interpreted as the count of participants who discontinued. The available summary also does not give event timing, duration, recurrence, or participant-level overlap among the listed terms.
12. What the Result Does, and Does Not, Mean
The results describe adverse events recorded in a single-group, open-label study of Ace-ER at 6 g/day in participants with GNE myopathy and severe ambulatory impairment. They provide a record of observed safety events during the stated follow-up: 1 participant with a serious TEAE, 26 with other TEAEs, and 0 deaths among the reported safety population of 42 participants at risk.
These observations do not establish that Ace-ER caused the events. The registry’s definition includes adverse events whether or not considered drug-related, and the study did not include a control group. Without a concurrent comparator, the data cannot determine how the event pattern differs from background occurrence, another treatment, or no study treatment. The open-label design also means treatment assignment was not masked.
The counts do not fully characterize how often events occurred over time, how long they lasted, whether they recurred, or how they affected individual participants. The listed serious-event terms and percentages add some descriptive detail, but the registry record does not provide enough information to reconstruct event-level patterns or determine whether terms refer to distinct participants.
The primary outcome is safety-focused. It does not establish changes in mobility, upper-extremity function, or self-care. Those are listed as secondary outcomes, but numerical results are not reported in the registry record. The same caution applies to the primary endpoint component concerning events leading to discontinuation: its count is not reported.
General statistical context: an observed count is an estimate from the participants studied, not a guarantee of the frequency in a larger population. No confidence intervals for the primary counts are reported in the registry record, so precision cannot be fully judged. The findings are best read as descriptive observations from this particular study and follow-up, with the limitations of its design and reporting.
13. Why This Trial Matters Statistically
This study illustrates why safety outcomes need to be interpreted in the context of both endpoint definitions and trial structure. A count of participants with an adverse event is clinically relevant as a description of what was recorded, but it is not a causal comparison. The single-group, open-label design makes that distinction especially important: the data show events after study treatment began, without a control group that could help describe the background event pattern under alternative conditions.
The registry separates serious TEAEs from other TEAEs and defines seriousness using specified outcomes, including hospitalization, life-threatening events, and significant incapacity or disability. This distinction matters because a total count of adverse events alone would not convey whether events met seriousness criteria. At the same time, seriousness should not be confused with severity, and neither category establishes drug causality.
The safety population and follow-up period also shape the meaning of the counts. The registry defines the safety set as enrolled participants who received at least 1 dose and gives a 48 Weeks timeframe with additional follow-up for some participants. Details of completeness and variation in observation are not reported in the registry record. Such information is important when considering how well a participant count captures exposure and follow-up.
The registry also lists functional outcomes and multiple analyses, but their numerical results and multiplicity procedures are not reported in the record. That limits the ability to interpret broader outcome patterns or assess how statistical testing was organized. The sample-size illustrations described for a hypothetical two-arm comparison do not replace the actual single-group design or establish the original design rationale.
Statistically, the main value of these results is their descriptive account of safety observations in this study population. Their importance lies in careful characterization, not in a controlled estimate of comparative risk or a conclusion about efficacy.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
Several trial-specific limitations affect interpretation. The study was open-label and single-group, with no randomized comparator. Therefore, the adverse-event counts cannot be contrasted with a concurrent control group, and causal attribution to Ace-ER cannot be established from these counts alone.
The registry lists 42 participants at risk for serious and other adverse events. A study of this size provides a limited basis for characterizing uncommon events. The record does not report confidence intervals, so the precision of the event estimates cannot be assessed from interval estimates. The listed count of 0 deaths is a description of this study record, not evidence that the risk of death is absent.
The primary endpoint includes TEAEs leading to discontinuation, but the corresponding count is not reported in the registry record. Event-level details, including timing, duration, recurrence, and participant overlap across serious-event terms, are also not reported. The listed serious-event terms each have a stated percentage, but the record does not explain their participant-level distribution.
The registry describes the follow-up timeframe but does not report the distribution of actual follow-up or how incomplete observation was handled. Missing-data procedures and sensitivity analyses are not reported. Although the safety population is defined, analysis populations for secondary outcomes are not reported in the record.
Finally, the registry lists secondary functional outcomes and multiple analyses, but their numerical results and any multiplicity adjustment are not reported. The study’s sample-size justification and detailed statistical analysis plan are also not reported in the registry record. These gaps limit interpretation beyond the descriptive safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Safety of Aceneuramic Acid Extended Release (Ace-ER; UX001) Tablets in Glucosamine (UDP-N-acetyl)-2-Epimerase (GNE) Myopathy (GNEM) (Also Known as Hereditary Inclusion Body Myopathy [HIBM]) Patients With Severe Ambulatory Impairment — NCT02731690.
- Registry record last updated 2019-02-19; status last verified 2019-02.
- Results first posted 2019-02-19.
- 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.
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18. Record Summary
NCT02731690 is a Phase 2, open-label, single-group study of aceneuramic acid extended-release (Ace-ER) in participants with GNE myopathy and severe ambulatory impairment. The registry lists 42 participants enrolled and a dose of 6 g/day. The study began on 2016-04-29, had a primary completion date of 2018-01-10, and is listed as terminated.
The primary endpoint counts participants with treatment-emergent adverse events, serious treatment-emergent adverse events, and events leading to discontinuation. The posted safety summary lists 1 participant with a serious TEAE, 26 with other TEAEs, and 0 deaths, with 42 participants at risk. Pyelonephritis, sepsis, and nephrolithiasis are each listed at 2.4% among the top serious-event terms.
These are descriptive safety observations without a randomized control group. The count for events leading to discontinuation, numerical secondary-outcome results, missing-data methods, confidence intervals, and multiplicity procedures are not reported in the registry record.