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 of UX003 Recombinant Human Beta-Glucuronidase (rhGUS) Enzyme Replacement Therapy in Subjects With Mucopolysaccharidosis Type 7, Sly Syndrome (MPS 7) (NCT02432144), a na phase 3 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 | NCT02432144 |
| Phase | Phase 3 |
| Condition | Sly Syndrome, MPS VII, Mucopolysaccharidosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ultragenyx Pharmaceutical Inc |
| Results posted | Yes |
2. Clinical Question
Population
Participants with Sly Syndrome, also identified in the registry record as MPS 7 or Mucopolysaccharidosis VII. The defined Full Analysis Set includes enrolled participants who received at least one dose of investigational product.
Intervention
UX003, described as recombinant human beta-glucuronidase enzyme replacement therapy. The recorded regimen was 4 mg/kg every other week.
Comparator
There was no separate comparator group. The study is recorded as single-group, with allocation listed as not applicable and masking as none.
Primary question
The primary objective was to evaluate long-term safety. The primary outcome counts participants with treatment-emergent adverse events, serious treatment-emergent adverse events, and treatment-emergent adverse events leading to discontinuation.
In practical statistical terms, the question is descriptive: what adverse events were recorded during UX003 treatment and the specified follow-up window? The registry describes treatment-emergent events as adverse events with onset during treatment, and defines the observation window as the period from the first study-drug dose until 30 days after the last dose. It reports a mean UX003 treatment duration of 100.5 weeks.
Because the study has no comparator group, its primary safety results do not estimate a difference between UX003 and another treatment or no treatment. They describe events among participants in this study. That distinction matters when interpreting both the event counts and the listed serious-event terms: the record can describe what occurred during the study, but the design alone cannot establish whether an event was caused by treatment.
3. Trial Design
This was a completed Phase 3, long-term, open-label treatment and extension study of UX003 in participants with MPS 7. The registry records a single-group model, no masking, and allocation as not applicable. The listed regimen was 4 mg/kg UX003 every other week. Enrollment was 12.
The primary objective was long-term safety evaluation. The primary outcome is framed as counts of participants with treatment-emergent adverse events, serious treatment-emergent adverse events, and treatment-emergent adverse events leading to discontinuation. A secondary outcome concerns percent change from baseline over time in urinary glycosaminoglycan excretion, specifically dermatan sulfate measured by liquid chromatography-tandem mass spectrometry. The registry lists 2 outcome measures and 5 analyses.
The registry records the study start as 2015-11-10 and primary completion as 2019-01-14, with status completed. It does not report a randomized allocation or a concurrent control group. The trial therefore supports a descriptive account of events and measurements within the treated group, not a randomized between-group estimate.
Open-label means masking was not used, as recorded in the study design. In general, knowledge of treatment assignment can affect how symptoms are noticed, reported, evaluated, or attributed, although the record does not quantify such effects. The extension and long-term treatment context also means that participants could have different durations of observation; the registry reports a mean treatment duration but does not give individual follow-up durations in the registry record for this analysis.
The registry does not report a protocol-based sample-size justification, a planned control comparison, or a detailed statistical analysis plan. Those omissions limit what can be said about the design rationale and planned inferential procedures. They do not change the central design fact: this is a single-group study whose primary focus is safety description.
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: Ten of 12 participants entered this extension study at study Week 0 with ongoing UX003 treatment for the prior 24 or 48 weeks in study UX003-CL301 \[NCT02230566\]; 2 participants had a large gap between studies (61 weeks between doses).
Overall Study
| Stage | UX003 |
|---|---|
| STARTED | 12 |
| COMPLETED | 11 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | UX003 |
|---|---|
| Participant Non-Compliance | 1 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: all enrolled participants who received at least one dose of investigational product in this study.
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 | UX003 |
|---|---|---|
| Participants analysed | 12 | |
| Age, Continuous | years | 16.56 (SD 5.466) |
| Sex: Female, Male: Female | Participants | 8 |
| Sex: Female, Male: Male | Participants | 4 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 6 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race/Ethnicity, Customized: White | Participants | 9 |
| Race/Ethnicity, Customized: Other, Not Specified | Participants | 3 |
| Urinary Glycosaminoglycans (uGAG) | g GAG/g creatinine | 1.54848 (SD 0.413237) |
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 From first dose of study drug until 30 days after the last dose of study drug. Mean duration of UX003 treatment was 100.5 weeks..
| 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, serious treatment-emergent adverse events, and treatment-emergent adverse events leading to discontinuation. A treatment-emergent adverse event is defined in the registry as an adverse event with onset during treatment. The recorded observation window runs from the first dose of study drug through 30 days after the last dose.
The registry defines an adverse event as an untoward medical occurrence, whether or not considered related to the drug. It defines serious events by specified outcomes, including death, a life-threatening event, hospitalization or prolonged hospitalization, persistent or significant incapacity or substantial disruption of normal life functions, a congenital anomaly or birth defect, or another important medical event. Event severity was graded using NCI CTCAE version 4.0, from mild through death.
Counting participants is useful for a safety summary because it describes how many people experienced an event, rather than how many event episodes occurred. The count does not by itself describe event duration, recurrence, severity beyond the serious-event classification, or the probability of an event under a different treatment. The registry record does not report the count of participants with events leading to discontinuation in the registry record for this analysis.
The primary outcome is appropriate to the stated safety objective as a descriptive measure of events observed during treatment and follow-up. It does not, by itself, determine whether an event was caused by UX003. The registry reports that mean treatment duration was 100.5 weeks, which gives context for the period over which participants were treated but does not replace individual exposure or time-to-event information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted adverse-event summary records 4 participants affected by serious events among 12 at risk. It also records 12 participants affected by other events among 12 at risk. These are descriptive counts from a single treated group. They should not be read as estimates of a treatment effect or as evidence of what would have occurred under another treatment.
The serious-event terms listed are Gastroenteritis, Head Injury, Headache, Asthmatic Crisis, Bronchospasm, and Interstitial Lung Disease. Each term is listed with a frequency of 8.3%. These are registry-listed frequencies, not a basis for assuming the terms are mutually exclusive or for adding them together. The record lists 0 deaths. A zero count in this study describes the observed record; it does not establish that the risk of death is absent.
The primary outcome includes events leading to discontinuation, but a discontinuation count is not reported in the registry record. Nor are confidence intervals or a formal comparative estimate reported in the registry record. Without an interval, the precision of the event counts cannot be summarized using an uncertainty range. Even if an interval were available, a single-group interval would describe uncertainty around a within-group quantity, not remove the lack of a control group.
General statistical interpretation: an event count is most informative when read alongside the number observed, the period at risk, event definitions, and the way events were collected. Here, the record supplies the at-risk counts and a study-wide mean treatment duration, but does not provide individual exposure times or detailed timing for each event. Thus the counts do not support a comparison of event rates adjusted for duration of exposure.
The findings are also conditioned on the Full Analysis Set definition: enrolled participants who received at least one dose. The record does not describe an analysis of people who enrolled but did not receive a dose. It does not report the missing-data approach, if any. These details matter when interpreting how well the displayed counts represent all people who entered the study.
The secondary urinary glycosaminoglycan outcome is described as percent change from baseline over time in dermatan sulfate excretion measured by liquid chromatography-tandem mass spectrometry. Numerical results for that outcome are not reported in the registry record details used for this interpretation. It should therefore not be used to extend the safety interpretation or to make a claim about clinical benefit.
Overall, the registry documents adverse events during long-term UX003 exposure in this study and identifies serious-event categories. The design and reported results do not establish causation, comparative safety, or a benefit-risk conclusion. Those questions require evidence beyond these descriptive single-group counts.
9. Statistical Methods Explained
What does a participant count represent?
The primary outcome is expressed as a count of participants with specified event categories. In general, this differs from counting event episodes: one participant may experience more than one event, while a participant count records whether a person is included in the category. A participant count is therefore a direct descriptive summary, but it does not show how many episodes occurred, how long events lasted, or whether they recurred.
The registry defines treatment-emergent events by onset during treatment and gives an observation window extending from the first dose until 30 days after the last dose. Applying a consistent window helps specify which events enter the summary. It does not establish that treatment caused the events, because the definition concerns timing rather than causation.
What does the serious-event classification add?
The registry’s seriousness definition is based on outcomes or clinical importance, including death, life-threatening events, hospitalization or prolonged hospitalization, substantial incapacity or disruption of normal life functions, congenital anomaly or birth defect, and important medical events. Seriousness is distinct from severity grading. The record says events were graded using NCI CTCAE version 4.0, with categories from mild to death. In general, seriousness asks about specified consequences or importance, while severity grading describes the intensity of an event. The two concepts should not be treated as interchangeable.
The serious-event summary and the listed serious-event terms answer different descriptive questions. The participant count indicates how many people were affected within the reported category. The terms identify event types and their listed frequencies. Without further detail, the terms should not be summed as though each necessarily occurred in a different participant, and the listed frequencies do not show event duration or relationship to treatment.
Why does the single-group design matter?
General statistical explanation: a comparison group helps distinguish outcomes observed under an intervention from outcomes that might also occur without that intervention or under another intervention. In this study, the record lists a single group and no randomized comparison. Consequently, the event counts describe the treated participants but do not estimate a difference between treatment groups. The open-label design also means masking was not used; the record does not quantify whether knowledge of treatment affected event reporting or assessment.
A within-group proportion or count can be useful for describing observed experience, but it is not a causal contrast. A causal interpretation would require assumptions and evidence that are not posted by the single-group design alone. No adjusted comparative effect, confidence interval, or hypothesis test is reported in the registry record details used.
How should precision be understood?
General statistical explanation: a confidence interval is a range of values compatible with the observed data under a specified statistical model. It conveys uncertainty around an estimate; it does not guarantee that the true value falls within the interval, and it does not correct a biased design. The registry record does not report confidence intervals for the adverse-event counts in the registry record for this analysis. As a result, the counts can be described, but their statistical precision cannot be characterized with a reported interval.
Small groups generally yield less precise estimates than larger groups, and rare events are particularly difficult to characterize from limited observations. This is a general principle, not an additional result about the study. The record reports enrollment of 12 and adverse-event at-risk counts of 12, but it does not report a precision calculation for these outcomes.
What do the planning illustrations mean?
General statistical explanation: sample-size calculations describe the amount of information a future design might need under stated assumptions. The registry-related planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect set as a stated fraction of the observed effect. For time-to-event outcomes it uses a total event count; for other outcomes it describes participants per arm. These assumptions describe a hypothetical two-arm planning exercise, not the design of this single-group study.
Such planning values are illustrations, not observed power. They do not show that the completed trial had a particular probability of detecting an effect, and they do not establish that the assumptions are appropriate for this study. The record does not report a protocol-based sample-size justification. A two-arm calculation should not be treated as evidence that this trial had a comparator or was designed for a randomized treatment contrast.
What statistical details are unavailable?
The registry record does not report the detailed statistical model or testing procedure for the primary endpoint, the handling of missing outcomes, or a multiplicity strategy. It also does not report event-level timing or individual exposure durations in the registry record used. These absences limit assessment of model assumptions, uncertainty, and any planned adjustment across outcomes or analyses. They should be treated as unreported details rather than filled in by assumption.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures and 5 analyses, but a strategy for controlling multiplicity is not reported in the registry record. Multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined. In general, more testing can increase the chance of obtaining a nominally notable result by chance if no adjustment or prioritization is used. That general concern does not show that any particular result is false; it explains why a prespecified analysis hierarchy or adjustment method can matter. The record details do not establish whether such a plan existed outside the registry entry.
The Full Analysis Set is defined as all enrolled participants who received at least one dose of investigational product. This identifies the population used for the primary outcome summary. The record does not report how participants who enrolled but did not receive a dose were handled in other analyses, or whether other analysis populations were defined.
A missing-data method is not reported in the registry record. It is therefore not possible to determine from these registry entries whether missing outcomes were excluded, imputed, or handled through another approach. General statistical explanation: missingness can affect interpretation when the chance that an observation is unavailable is related to participant characteristics or outcomes. The method used, and assumptions underlying it, can influence estimates and their uncertainty. No particular missingness mechanism should be inferred for this study.
The secondary outcome is described as percent change from baseline over time in urinary glycosaminoglycan excretion, measured for dermatan sulfate by liquid chromatography-tandem mass spectrometry. Numerical results and details of missing-data handling for this outcome are not reported in the registry record details used. These gaps prevent a fuller appraisal of how repeated measurements or incomplete follow-up were analyzed.
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 |
|---|---|---|---|
| UX003 | 4 | 12 | 33.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| UX003 | 0 of 12 |
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 |
|---|---|
| UX003 | 12 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | UX003 |
|---|---|---|
| Gastroenteritis | Infections and infestations | 1 of 12 |
| Head Injury | Injury, poisoning and procedural complications | 1 of 12 |
| Headache | Nervous system disorders | 1 of 12 |
| Asthmatic Crisis | Respiratory, thoracic and mediastinal disorders | 1 of 12 |
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | 1 of 12 |
| Interstitial Lung Disease | Respiratory, thoracic and mediastinal disorders | 1 of 12 |
| Urticaria | Skin and subcutaneous tissue disorders | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | UX003 |
|---|---|---|
| Upper Respiratory Tract Infection | Infections and infestations | 7 of 12 |
| Infusion Site Extravasation | General disorders | 5 of 12 |
| Vomiting | Gastrointestinal disorders | 4 of 12 |
| Cough | Respiratory, thoracic and mediastinal disorders | 4 of 12 |
| Urticaria | Skin and subcutaneous tissue disorders | 4 of 12 |
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | 3 of 12 |
| Rhinitis | Infections and infestations | 3 of 12 |
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | 3 of 12 |
| Ear Pain | Ear and labyrinth disorders | 2 of 12 |
| Conjunctivitis Allergic | Eye disorders | 2 of 12 |
Serious events with the highest arm-level rate: gastroenteritis (8.3%), head injury (8.3%), headache (8.3%), asthmatic crisis (8.3%), bronchospasm (8.3%).
The serious-event summary records 4 participants affected among 12 at risk. The registry lists Gastroenteritis, Head Injury, Headache, Asthmatic Crisis, Bronchospasm, and Interstitial Lung Disease as serious-event terms, each with a listed frequency of 8.3%. The record also lists 0 deaths. These figures describe events recorded during the study; they do not establish that UX003 caused them or that the same event pattern would occur in another group.
The listed term frequencies should not be added together. The registry entries do not establish whether terms overlap within participants, and a term frequency is not the same as a count of distinct participants. The serious-event participant count and the term-level frequencies therefore should be read as separate descriptions.
The observation window extends from the first dose until 30 days after the last dose, and the mean duration of UX003 treatment was 100.5 weeks. Individual exposure times and event timing are not reported in the registry record details used here, so the counts cannot be interpreted as exposure-adjusted rates. A zero death count describes what was recorded in this study; it does not demonstrate zero risk.
The registry defines seriousness by specified consequences or importance and separately describes CTCAE severity grading. An event’s seriousness should not be assumed to indicate a particular severity grade. The count of participants with treatment-emergent events leading to discontinuation is not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The results describe safety observations during treatment with UX003 in a single-group, open-label study of participants with MPS 7. The registry records 4 participants with serious events among 12 at risk, and 12 participants with other events among 12 at risk. It lists several serious-event terms and records 0 deaths. The mean treatment duration was 100.5 weeks, and events were observed through 30 days after the last dose.
These findings can be used as a record of what was observed in this study under its stated event definitions and observation window. They do not establish that UX003 caused a reported event. Because there was no concurrent comparator group, they also do not estimate how the event experience differed from another treatment or from no treatment.
The results do not show that an event cannot occur because no deaths were recorded, and the listed term frequencies do not show that terms occurred in separate people. The record does not provide confidence intervals for the event counts or an exposure-adjusted analysis. Thus, the degree of statistical uncertainty around the reported counts is not quantified in the registry entries.
The primary objective concerns long-term safety. The secondary outcome concerns change over time in urinary glycosaminoglycan excretion, but numerical results for that measure are not reported in the registry record details used. The available results therefore do not support a conclusion about that outcome, clinical benefit, or overall benefit-risk.
In general, a single-group study can contribute descriptive information, especially when the outcome is the occurrence of safety events during a defined treatment period. Its limits are equally important: observed events may reflect treatment, the underlying condition, background events, or other factors, and the design does not separate those explanations. Interpretation should remain confined to the recorded observations and study context.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction in clinical statistics: a study can provide useful descriptive safety information without estimating a comparative treatment effect. The registry identifies a defined treatment regimen, an event observation window, and a primary outcome based on participant counts. Those features allow readers to understand what was counted and over what period, while the single-group design sets a clear boundary on causal interpretation.
It also demonstrates why endpoint definitions matter. “Treatment-emergent” specifies timing, whereas the registry’s adverse-event definition does not require that an event be considered drug related. Seriousness is defined through specified consequences or medical importance, while severity is graded separately. Keeping these concepts distinct avoids turning a timing rule or event classification into a claim about causation.
Long-term treatment duration provides context for safety observation, but a mean duration does not reveal individual exposure patterns. Without individual event timing or exposure-adjusted rates, participant counts cannot answer whether event rates changed with time at risk. The registry record also does not report confidence intervals, a detailed statistical plan, or a missing-data method in the registry record for this analysis.
Finally, the planning assumptions described for a two-arm sample-size illustration should not be confused with the actual single-group design. General statistical lesson: planning calculations depend on a target comparison and assumptions about allocation, effect size, and analysis. They are not observed power and cannot supply evidence that a treatment effect was present. The trial matters statistically as a case in how design, endpoint definition, and reporting scope shape what a safety result can support.
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 main limitation is the absence of a concurrent comparator. With a single group and no masking, the reported events are descriptive observations; the design does not estimate a relative risk or establish causation. The registry identifies no randomized comparison, so the results should not be framed as a controlled treatment contrast.
The enrolled group was 12, and the adverse-event summary lists 12 at risk. This is a limited basis for characterizing uncommon events or estimating event frequencies precisely. Confidence intervals are not reported in the registry record details used here, so uncertainty around the counts cannot be assessed from reported intervals.
The registry reports a mean treatment duration of 100.5 weeks but does not provide individual exposure durations or event timing in the registry record. Counts therefore cannot be adjusted for differences in time at risk. The listed serious-event terms each have a frequency of 8.3%, but the record details do not establish whether participants could contribute to more than one term; the frequencies should not be summed.
The primary outcome includes treatment-emergent adverse events leading to discontinuation, but the count for that category is not reported in the registry record. The missing-data approach and a detailed statistical analysis plan are also not reported. The record lists a secondary urinary glycosaminoglycan outcome, but its numerical results are not available in the registry record used for this analysis. These reporting gaps restrict evaluation of the full outcome set and of analysis choices.
Finally, the planning illustration uses assumptions for a hypothetical two-arm design, whereas this study is single-group. Those calculations should not be taken as a design justification or as observed power for the completed study.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of UX003 Recombinant Human Beta-Glucuronidase (rhGUS) Enzyme Replacement Therapy in Subjects With Mucopolysaccharidosis Type 7, Sly Syndrome (MPS 7) — NCT02432144.
- Registry record last updated 2020-07-30; status last verified 2020-07.
- Results first posted 2019-07-30.
- 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
The registry record describes a completed Phase 3, open-label, single-group study of UX003 in participants with MPS 7. The recorded regimen was 4 mg/kg every other week, and enrollment was 12. The primary objective was long-term safety evaluation; the primary endpoint counts participants with treatment-emergent adverse events, serious treatment-emergent adverse events, and events leading to discontinuation.
The adverse-event summary records 4 participants affected by serious events among 12 at risk, 12 affected by other events among 12 at risk, and 0 deaths. Six serious-event terms are listed, each with a frequency of 8.3%. Mean UX003 treatment duration was 100.5 weeks. The record does not report a comparator, a discontinuation count, confidence intervals, a missing-data method, or numerical results for the listed secondary urinary glycosaminoglycan outcome in the registry record used for this analysis.