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 Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Participants With Lysosomal Acid Lipase Deficiency (NCT01307098), a non-randomized phase 1, phase 2 study. The primary outcome is Number Of Participants Reporting TEAEs And Infusion-Related Reactions (IRRs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01307098 |
| Phase | Phase 1, Phase 2 |
| Condition | Cholesterol Ester Storage Disease(CESD), Lysosomal Acid Lipase Deficiency, LAL-Deficiency |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 9 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alexion Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Adults with liver dysfunction due to lysosomal acid lipase (LAL) deficiency. The registry describes the Safety Analysis Set as participants who received any full or partial dose of sebelipase alfa. Enrollment was 9, and the brief summary says the target was 9 evaluable participants.
Intervention
Weekly infusions of sebelipase alfa were given in dose cohorts: 0.35 mg/kg, 1 mg/kg, and 3 mg/kg. The study was open-label and designed to examine these three doses.
Comparator
There was no randomized control group. The registry identifies the study as non-randomized and single-group, with dose cohorts rather than a like-for-like control comparison. Differences across cohorts should not be read as randomized treatment effects.
Primary question
The primary safety question was how many participants reported treatment-emergent adverse events (TEAEs), including serious adverse events, and infusion-related reactions (IRRs), and how many discontinued because of a TEAE. The timeframe was screening up to Day 52. An IRR was defined by timing during or within 4 hours after infusion and an investigator assessment of at least possible relation to study drug.
This is a safety and tolerability question, not a randomized efficacy comparison. The registry record describes the study as the first clinical study of sebelipase alfa for LAL deficiency. That context helps explain the focus on adverse events, infusion reactions, and dose escalation. It does not, by itself, establish how doses were selected or how the study’s sample size was justified; those details are not reported in the registry record.
3. Trial Design
NCT01307098 is recorded as a completed Phase 1 and Phase 2 study sponsored by Alexion Pharmaceuticals, Inc. It began on 2011-04-25, and primary completion was recorded as 2012-01-06. The official title describes an open-label, multicenter study in adults with liver dysfunction due to LAL deficiency. Allocation was non-randomized, masking was none, and the model was single-group.
The intervention was administered in dose cohorts: 0.35 mg/kg, 1 mg/kg, and 3 mg/kg of sebelipase alfa, each by once-weekly infusion. The registry’s brief summary characterizes the study as an open-label dose-escalation study designed to examine three doses. Enrollment was 9; the summary states that the target was 9 evaluable participants. The record does not give the number assigned to each cohort as an enrollment plan, or describe the rules for progressing between doses.
Because assignment was not randomized and there was no control group, the cohorts are not a like-for-like comparison. The participants’ observed safety counts can be described by dose cohort, but contrasts between cohorts may reflect factors other than dose. The registry record does not report a statistical plan explaining any dose comparisons, adjustment for baseline differences, or a method for drawing causal conclusions.
The primary safety endpoint covered screening up to Day 52. It focused on participants reporting TEAEs, including serious adverse events, IRRs, and discontinuation due to a TEAE. The adverse-event description defines an IRR using both an infusion-related time window and investigator-assessed relation to the study drug. Further detail on follow-up outside the stated timeframe, dose escalation procedures, and analysis timing is 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: Participants were screened for eligibility for enrollment in this study (LAL-CL01). Nine participants met all enrollment criteria and were enrolled and allocated to 1 of 3 cohorts.
Overall Study
| Stage | Sebelipase Alfa 0.35 mg/kg | Sebelipase Alfa 1 mg/kg | Sebelipase Alfa 3 mg/kg |
|---|---|---|---|
| STARTED | 3 | 3 | 3 |
| Received at Least 1 Dose of Study Drug | 3 | 3 | 3 |
| COMPLETED | 3 | 3 | 3 |
| NOT COMPLETED | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set: All participants who received any full or partial dose of sebelipase alfa 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.
Population: All participants who received any full or partial dose of sebelipase alfa in this study.
| Characteristic | Unit | Sebelipase Alfa 0.35 mg/kg | Sebelipase Alfa 1 mg/kg | Sebelipase Alfa 3 mg/kg | Total |
|---|---|---|---|---|---|
| Participants analysed | 3 | 3 | 3 | 9 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 | 3 | 3 | 9 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Age, Continuous | years | 32.3 (SD 7.57) | 35.3 (SD 14.22) | 27.0 (SD 12.17) | 31.6 (SD 10.74) |
| Sex: Female, Male: Female | Participants | 1 | 1 | 1 | 3 |
| Sex: Female, Male: Male | Participants | 2 | 2 | 2 | 6 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 3 | 3 | 9 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 3 | 3 | 3 | 9 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number Of Participants Reporting TEAEs And Infusion-Related Reactions (IRRs), measured over Screening up to Day 52.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants reporting TEAEs and IRRs, with safety assessed from screening up to Day 52. The description also notes serious adverse events and participants who discontinued because of a TEAE. An IRR is defined as an adverse event occurring between the start of infusion and 4 hours after its completion, with the investigator judging it at least possibly related to study drug.
Participant counts are a direct way to describe how many people in a safety population experienced an event during the stated observation period. They are useful in an early dose-escalation study because safety and tolerability are central questions, and the counts can be presented by dose cohort. They do not, on their own, convey how often events occurred for an individual participant, their duration or severity, or whether one event category overlaps another.
The posted adverse-event figures distinguish serious events from other non-serious events. The registry record does not give a separate numerical result for TEAEs, IRRs, or discontinuations in the primary endpoint description. Those results should therefore not be inferred from the serious and other non-serious counts. The detailed summary of serious and other non-serious adverse events regardless of causality is identified as being in the Reported Adverse Events module.
As a general statistical point, event counts are descriptive: they depend on who was included in the safety population and how long participants were observed. Small cohort counts can change substantially with the experience of an individual participant. The registry record does not report uncertainty intervals for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety figures list 3 participants at risk for serious adverse events in each dose cohort, with 0 affected participants in each cohort. For other non-serious adverse events, the reported counts are 1 of 3 at 0.35 mg/kg, 3 of 3 at 1 mg/kg, and 3 of 3 at 3 mg/kg. These are participant counts, not counts of all event occurrences.
The pattern is descriptive. It does not establish that the higher doses caused more non-serious events, or that the lower dose was safer. Assignment was non-randomized, and the study did not include a control group. The registry record does not report cohort-specific baseline characteristics or an adjusted analysis that could help account for differences between participants. With only the reported counts, the reasons for any differences cannot be separated from chance, participant characteristics, exposure, or other factors.
No participants are listed as having a serious adverse event in any cohort in the posted figures. This is not evidence that serious events cannot occur. The number of participants exposed in each cohort was limited, and the record does not report uncertainty intervals around the counts. In general, observing no events in a small group still leaves uncertainty about the underlying risk.
The counts for other non-serious events indicate that such events were reported among participants in the 1 mg/kg and 3 mg/kg cohorts and among a participant in the 0.35 mg/kg cohort. They do not show how many events each participant had, which events were considered treatment-emergent, or whether they were judged related to sebelipase alfa. The posted figures should not be treated as a substitute for event descriptions or investigator assessments.
The primary endpoint also included IRRs and discontinuations due to TEAEs, but separate numerical results for those components are not reported in the registry record. The serious-event terms list is empty, so specific serious-event terms are not available in the record. Death counts are not reported in the registry record. These absences limit the scope of interpretation: the available counts support a narrow description of reported participant-level safety categories, not a complete account of every primary endpoint component.
The trial’s completed status and enrollment do not change these interpretive limits. Completion indicates the registry status, not that every safety question is resolved. No efficacy conclusion can be drawn from the safety counts, and the registry record does not report a randomized efficacy comparison.
9. Statistical Methods Explained
For a binary safety outcome, each participant can be classified according to whether the event was reported during the defined period. The resulting count describes participants with the event, while the at-risk count describes the participants represented for that category. In this study, the posted serious and other non-serious adverse-event figures are presented by dose cohort. The primary endpoint is also framed in terms of participant counts.
What does a participant count capture?
A participant count answers whether an event category was reported for a person; it does not necessarily count every occurrence. A participant with repeated events may still contribute to a count of participants with at least one event only once, depending on the endpoint’s coding rules. The registry record does not explain event-level counting rules for the displayed adverse-event figures, so the safest reading is to use them as participant counts, as labeled, rather than to infer the total number of episodes.
Categories can also overlap. A participant may have more than one kind of event, and the same event may be described in more than one clinically relevant way. The registry record does not say whether the serious, other non-serious, TEAE, and IRR categories are mutually exclusive. Therefore, adding category counts would not be an appropriate way to estimate a total number of affected participants, and no such total is reported.
Why does the denominator matter?
Counts are most interpretable alongside the population to which they apply. The Safety Analysis Set is defined as all participants who received any full or partial dose of sebelipase alfa. The adverse-event figures list 3 participants at risk in each cohort. A reader should not assume that the enrolled population and every endpoint-specific analysis population are identical unless the registry explicitly states that they are. The record gives the safety-set definition, but does not provide additional participant-flow detail or explain whether any participant was excluded from a particular endpoint analysis.
Observation time also matters. The primary endpoint timeframe is screening up to Day 52. A participant count over that period is not a rate per unit of follow-up, and it does not describe risk beyond that period. The registry record does not report a person-time analysis or an event-time analysis for this endpoint. General statistical practice distinguishes a simple participant count from a rate that accounts for different lengths of exposure; the posted result is described as a count.
How should cohort differences be interpreted?
Randomization is a method for creating comparable groups, on average, by assigning participants through chance. This study is explicitly non-randomized, open-label, and single-group. Its dose cohorts are not randomized comparator arms. As a general statistical principle, a difference in observed counts between non-randomized cohorts can reflect more than the dose: participant characteristics, enrollment sequence, exposure, and chance may all contribute. The registry record does not report an adjustment strategy that would address these possibilities.
Open-label means masking was none in the registry record. In general, knowing the administered treatment can influence event reporting, clinical assessment, or decisions about whether an event is related to treatment. That possibility does not show that assessments were biased in this trial; it is a design consideration when interpreting subjective or investigator-assessed outcomes. The IRR definition specifically includes an investigator judgment of at least possible relation to study drug.
What does uncertainty mean for these counts?
A confidence interval is a statistical range intended to express uncertainty around an estimate under a stated method and assumptions. General interpretation should consider both the observed count and how much information supports it. With a limited number of participants in a cohort, an individual participant’s experience can noticeably change the observed pattern. The registry record does not report confidence intervals or another uncertainty measure for these safety counts. It is therefore not possible to use the registry’s posted figures to assess their precision numerically.
For binary outcomes, methods often rely on assumptions about the event probability and the way participants were sampled or assigned. In a non-randomized dose-escalation study, a simple comparison of cohort proportions would not remove confounding or make the cohorts exchangeable. No inferential test or adjusted treatment-effect analysis is reported in the registry record. Any recalculation from the posted counts would be an unadjusted description, not a replacement for a sponsor analysis; the record lists no analyses for this outcome.
How do planning calculations differ from trial results?
A sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, allocation, significance level, and analysis method. It does not describe the observed number of participants who experienced an event, nor does it show the probability that a treatment effect is real. The registry record’s planning-illustration assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a fraction of the observed effect. Those assumptions are not a report of the trial’s own design rationale or an observed-power analysis. The record does not report the trial’s sample-size justification or its own statistical plan.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one outcome measure and no analyses. It does not report a plan for handling multiplicity, such as whether there were multiple confirmatory hypotheses, a hierarchy of tests, or an adjustment for repeated testing. Since no inferential analysis is listed, the record does not establish that a multiplicity procedure was used or that one was unnecessary. The primary safety endpoint itself includes several related components: TEAEs, serious adverse events, IRRs, and discontinuation due to a TEAE. Separate numerical results for all of those components are not reported in the registry record.
Missing-data handling is not reported in the registry record. There is no description of whether participants with incomplete follow-up were included for the period they were observed, how missing adverse-event information was handled, or whether any imputation method was used. The absence of a reported missing-data method should not be interpreted as proof that there were no missing observations.
The Safety Analysis Set includes participants who received any full or partial dose. That definition identifies the population intended for safety assessment, but the record does not provide detailed participant flow or a separate analysis population for every outcome. Enrollment was 9, and the brief summary states a target of 9 evaluable participants. These statements do not establish the number with complete follow-up for each endpoint.
Because the study was non-randomized and single-group, the record does not report an intention-to-treat comparison between randomized arms. It also does not report an adjusted analysis that accounts for differences between dose cohorts. Any planning illustration based on an observed effect should be understood as a planning exercise, not observed power; the registry record does not report a trial-specific statistical analysis plan.
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 |
|---|---|---|---|
| Sebelipase Alfa 0.35 mg/kg | 0 | 3 | 0.0% |
| Sebelipase Alfa 1 mg/kg | 0 | 3 | 0.0% |
| Sebelipase Alfa 3 mg/kg | 0 | 3 | 0.0% |
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 |
|---|---|
| Sebelipase Alfa 0.35 mg/kg | 1 of 3 |
| Sebelipase Alfa 1 mg/kg | 3 of 3 |
| Sebelipase Alfa 3 mg/kg | 3 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sebelipase Alfa 0.35 mg/kg | Sebelipase Alfa 1 mg/kg | Sebelipase Alfa 3 mg/kg |
|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 1 of 3 | 2 of 3 | 0 of 3 |
| Headache | Nervous system disorders | 0 of 3 | 1 of 3 | 2 of 3 |
| Nausea | Gastrointestinal disorders | 1 of 3 | 0 of 3 | 1 of 3 |
| Abdominal discomfort | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 1 of 3 |
| Abdominal distension | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 1 of 3 |
| Abdominal pain | Gastrointestinal disorders | 0 of 3 | 1 of 3 | 0 of 3 |
| Abdominal pain lower | Gastrointestinal disorders | 0 of 3 | 1 of 3 | 0 of 3 |
| Dyspepsia | Gastrointestinal disorders | 0 of 3 | 1 of 3 | 0 of 3 |
| Flatulence | Gastrointestinal disorders | 0 of 3 | 1 of 3 | 0 of 3 |
| Rectal haemorrhage | Gastrointestinal disorders | 0 of 3 | 1 of 3 | 0 of 3 |
The serious adverse-event figures report 0 affected participants among 3 at risk in each of the three dose cohorts. This describes the posted participant counts; it does not establish that the risk of a serious event is absent. The serious-event terms list is empty, and specific serious-event terms are not reported in the registry record.
For other non-serious adverse events, the posted counts are 1 of 3 in the 0.35 mg/kg cohort, 3 of 3 in the 1 mg/kg cohort, and 3 of 3 in the 3 mg/kg cohort. These categories should be read as participant counts, not as a count of every episode. The record does not report whether the other non-serious events were treatment-emergent, judged related to treatment, or infusion-related, so those labels should not be assigned to them based on these figures alone.
The primary endpoint description includes IRRs and discontinuations due to TEAEs, but separate counts for those outcomes are not reported in the registry record. Death counts are also not reported in the registry record. As a general statistical caution, participant counts in limited cohorts are imprecise descriptions of event experience and do not by themselves support comparisons of underlying risk between doses.
12. What the Result Does, and Does Not, Mean
The registry record supports a descriptive account of safety events reported among participants in this open-label, non-randomized dose-escalation study. It records no serious adverse-event participants among those listed at risk in each cohort, and it reports other non-serious adverse events in participants across the dose cohorts. The primary endpoint was intended to monitor TEAEs, including serious events, IRRs, and discontinuations attributed to TEAEs, over screening up to Day 52.
These observations do not establish that sebelipase alfa caused or prevented any event. They do not demonstrate that one dose is safer than another, because the cohorts were not randomized and there was no control group. The registry record does not report an adjusted comparison, uncertainty intervals, or separate numerical results for every component of the primary endpoint. The observed counts should therefore be read as descriptions of the listed participants, not as definitive estimates of comparative risk.
The data also do not answer questions about long-term safety, event frequency per infusion, event severity beyond the serious/non-serious distinction, or efficacy. The primary timeframe is screening up to Day 52, and no result for follow-up beyond that timeframe is reported in the registry record. The event figures do not show how many episodes occurred or whether events were considered related to study drug.
In general, an absence of observed serious events in a limited group does not establish that serious events cannot occur. Likewise, observing non-serious events does not establish that the treatment caused them. The registry’s design and reporting support cautious description of this early clinical safety experience, while leaving substantial uncertainty about comparisons, attribution, and outcomes not separately reported.
13. Why This Trial Matters Statistically
Statistically, NCT01307098 illustrates the role of descriptive safety evidence in an early dose-escalation study. The study examined three weekly infusion doses of sebelipase alfa in adults with liver dysfunction due to LAL deficiency, with safety and tolerability as the primary focus. Participant counts can communicate what was reported in each cohort without implying that the study was designed to estimate a randomized treatment effect.
The record also makes clear why design labels matter. Non-randomized allocation, no masking, and a single-group model limit the kinds of comparisons that can be supported. Even when counts are presented by dose, the cohorts do not function as randomized controls. Differences across them remain descriptive unless a suitable analysis and design justify stronger conclusions; such an analysis is not reported in the registry record.
The endpoint definition adds another statistical lesson: a composite safety description may encompass event categories with different meanings. TEAEs, serious adverse events, IRRs, and discontinuations are not interchangeable outcomes. The IRR definition includes both a specific time window and investigator assessment. Separate numerical results for every listed component would help readers understand the safety profile, but those results are not reported in the registry record.
Finally, the study highlights the distinction between planning and evidence. A planning illustration based on an observed effect is not observed power, and its assumptions do not substitute for a trial-specific sample-size rationale or statistical plan. The registry record does not report those details. Careful interpretation therefore depends on separating the observed participant counts from assumptions, unreported analyses, and questions the design was not set up to answer.
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 cohort counts are limited in scale: the registry lists 3 participants at risk in each dose cohort. Such counts provide only a narrow description of the participants observed and do not support precise estimates of event risk. No confidence intervals or other uncertainty measures are reported for the endpoint.
The absence of randomization and a control group prevents a like-for-like treatment comparison. Cohort differences cannot be attributed to dose alone from the posted counts. The record does not report baseline characteristics by cohort, adjustment for potential confounding, or details about how participants entered or progressed through the dose cohorts.
The study was open-label, with no masking. The record does not describe procedures that might reduce the influence of treatment knowledge on event reporting or investigator assessment. This is especially relevant to the IRR definition, which includes an investigator judgment about possible relation to study drug.
The registry record does not report separate numerical results for TEAEs, IRRs, or discontinuations due to TEAEs, despite their inclusion in the primary endpoint description. It also does not provide specific serious-event terms, death counts, event-level detail, or a missing-data method. The stated timeframe is screening up to Day 52, so the posted endpoint does not establish outcomes beyond that period.
Finally, the record does not report a trial-specific statistical analysis plan, sample-size justification, multiplicity approach, or inferential comparison. These omissions limit assessment of precision and analysis choices. They do not imply that particular procedures were or were not used outside what the registry record reports.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Participants With Lysosomal Acid Lipase Deficiency — NCT01307098.
- Registry record last updated 2018-12-11; status last verified 2018-12.
- Results first posted 2018-12-11.
- 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
NCT01307098 was a completed, open-label, non-randomized Phase 1 and Phase 2 study of sebelipase alfa in adults with liver dysfunction due to LAL deficiency. It used a single-group dose-escalation design with weekly infusion cohorts of 0.35 mg/kg, 1 mg/kg, and 3 mg/kg. Enrollment was 9, and the brief summary states a target of 9 evaluable participants.
The primary safety endpoint concerned participants reporting TEAEs, serious adverse events, IRRs, and discontinuation due to TEAEs from screening up to Day 52. The posted adverse-event counts list 0 serious-event participants among 3 at risk in each cohort. Other non-serious event counts are 1 of 3, 3 of 3, and 3 of 3 across the dose cohorts, respectively.
The record does not report separate results for every primary endpoint component, uncertainty intervals, missing-data handling, or a statistical analysis plan. The non-randomized design does not support a controlled dose comparison from these counts.