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 Safety and Tolerability of Olipudase Alfa in Pediatric and Adult Participants With Acid Sphingomyelinase Deficiency (ASMD) Who Completed the DFI12712 or the LTS13632 Study in France (NCT06949358), a na phase 2 study. The primary outcome is Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT06949358 |
| Phase | Phase 2 |
| Condition | Acid Sphingomyelinase Deficiency |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sanofi |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned pediatric and adult participants with acid sphingomyelinase deficiency (ASMD) in France who had completed the DFI12712 or LTS13632 study. The registry record reports enrollment of 3 participants. For the primary safety outcome, the defined analysis population included enrolled participants who received at least one partial or total infusion of olipudase alfa in this study.
Intervention
Participants received olipudase alfa by intravenous infusion every 2 weeks. The study was open-label, so treatment was not masked.
Comparator
There was no comparison group. The study is recorded as single-group, with allocation listed as not applicable. Its results therefore describe safety outcomes during treatment and follow-up, rather than a contrast between olipudase alfa and another treatment or control.
Primary question
The primary question was how many participants experienced adverse events (AEs) and serious adverse events (SAEs) during the defined safety period. An AE was an untoward medical occurrence temporally associated with study-drug use, whether or not considered related to the drug. An SAE was an AE meeting criteria such as death, a life-threatening event, hospitalization or its prolongation, persistent or significant disability, congenital anomaly or birth defect, or another medically important event.
The study’s stated purpose was to evaluate safety and tolerability while providing olipudase alfa to participants who had completed the earlier studies. According to the registry summary, the follow-up period covered the time until olipudase alfa reimbursement became available in France; if reimbursement was not obtained, the study ended 5 years after starting. The primary outcome does not assess comparative efficacy. With no control group, the study can describe observed events among participants in this follow-up, but cannot establish how those outcomes compare with an untreated group or another treatment.
3. Trial Design
This was a completed phase 2, open-label, single-group study in France. The registry record lists Sanofi as sponsor and enrollment of 3 participants. Eligible participants were pediatric or adult patients with ASMD who had completed the DFI12712 or LTS13632 study. Olipudase alfa was administered intravenously every 2 weeks. The record lists allocation as not applicable and masking as none; there was no randomized or masked comparator group.
The study was intended to provide enzyme replacement therapy and evaluate safety and tolerability during the period between completion of the earlier study and olipudase alfa reimbursement in France. If reimbursement was not obtained, the study ended 5 years after starting. The registry dates are a study start of 2021-11-18 and primary completion of 2025-04-08, with status recorded as completed. The primary safety timeframe ran from informed-consent signature, designated Day 0, to the end of each participant’s safety follow-up, up to approximately 40 months. Visits were scheduled every 2 weeks.
The primary outcome was a participant count: participants with AEs and participants with SAEs. Such counts describe how many participants were affected, not the total number of event episodes. The registry record defines a safety analysis set as enrolled participants who received at least one partial or total infusion of olipudase alfa in this study. It does not describe a between-group treatment contrast or a randomized allocation procedure. The rationale for the enrollment target, any formal sample-size justification, and the 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.
Before assignment: A total of 3 participants with acid sphingomyelinase deficiency (ASMD) who completed DFI12712 (NCT02004691) or LTS13632 (NCT02004704) study were enrolled in this study.
Overall Study
| Stage | Olipudase Alfa |
|---|---|
| STARTED | 3 |
| COMPLETED | 3 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: The Safety analysis set included all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current 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: Age and sex was collected for all enrolled participants.
| Characteristic | Unit | Olipudase Alfa |
|---|---|---|
| Participants analysed | 3 | |
| Age, Customized: 9-24 years | Participants | 3 |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 1 |
| Race and Ethnicity Not Collected | Participants | — |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over From the signature of informed consent (Day 0) up to end of safety follow-up per participant, up to approximately 40 months.
| 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 adverse events and serious adverse events during safety follow-up. An AE is defined broadly as an untoward medical occurrence temporally associated with study-drug use, whether or not the event is considered related to the drug. An SAE is an AE meeting specified seriousness criteria, including death, a life-threatening event, inpatient hospitalization or its prolongation, persistent or significant disability, congenital anomaly or birth defect, or another medically important event.
Participant counts are useful in safety monitoring because they indicate how many people experienced events, while separating serious events from other adverse events. They do not, by themselves, describe the number of event episodes, the duration or severity of each event, or whether an event was judged related to treatment. The registry’s endpoint is therefore a descriptive safety measure rather than a measure of treatment benefit or comparative risk.
The timeframe began at informed-consent signature and continued to the end of each participant’s safety follow-up, up to approximately 40 months. The primary outcome’s stated population was the safety analysis set: enrolled participants who received at least one partial or total olipudase alfa infusion in the current study. Whether event counts were separately analyzed by timing, severity beyond the SAE distinction, or relationship to treatment is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety counts record 0 participants with an SAE among 3 at risk for the serious-event outcome. For the other-adverse-event category, 3 participants were at risk and 3 were recorded as affected. The record also reports 0 deaths. These are participant counts: they do not give the total number of event episodes, and the other-adverse-event count should not be read as a count of distinct event types or episodes.
The serious-event result is a descriptive observation for this single-group follow-up. It does not demonstrate that serious events could not occur, nor does it estimate how the serious-event experience would differ under another treatment or without treatment. With a small enrolled group and no comparator, the record offers limited information about the frequency of uncommon outcomes or about comparative safety. A confidence interval is not reported in the registry record, so no interval estimate of uncertainty is available to interpret alongside the count.
The record reports all participants at risk for the other-adverse-event category as affected, but does not provide event-level descriptions in the listed serious-event terms, and the serious-event terms list is empty. The endpoint definition permits AEs that are not considered related to study drug; the participant count alone therefore cannot establish that an event was caused by olipudase alfa. Likewise, absence of a recorded SAE participant does not mean there were no AEs: the posted counts distinguish the serious category from other adverse events.
These results should be read in the context of the follow-up’s purpose and design. Participants had completed earlier studies, received olipudase alfa in an open-label setting, and had no concurrent control group. The counts describe observed safety outcomes over the registry-defined follow-up, which extended from consent to the end of safety follow-up, up to approximately 40 months. The record does not report how long each participant contributed observation or whether all participants completed the same follow-up duration.
Accordingly, the figures support a narrow statement about what was recorded in this study: no participant was listed with an SAE, while all participants at risk were listed in the other-adverse-event category. They cannot establish comparative risks, treatment causality, or safety in populations beyond the study participants. The results also do not answer an efficacy question, because the primary endpoint measures adverse events rather than clinical benefit.
9. Statistical Methods Explained
The primary outcome is a count of participants with events, not a continuous measurement. Each participant is classified according to whether an event in the relevant category was recorded during the defined safety period. This makes the outcome easy to read descriptively, but it does not convey how many event episodes occurred in a participant or how long an event lasted. The registry’s serious and other adverse-event categories should therefore be interpreted as participant-level counts.
What does a participant count tell the reader?
A participant count describes the number of people in the analysis set who met the outcome definition. The number at risk identifies the group against which that count is understood. The serious-event results list 3 at risk and 0 affected; the other-adverse-event results list 3 at risk and 3 affected. No percentage or comparative effect estimate is needed to state these observed counts, and none should be inferred as a comparison with another group because the study had no comparator.
Counts can be informative in a safety follow-up, particularly when the question is whether participants experienced serious events. However, counts do not capture all clinically relevant detail. Multiple events in one participant may contribute only one affected participant to a participant-level count. The registry record does not report the number of event episodes, their individual durations, or a breakdown of non-serious events by type. The listed serious-event terms are empty; this does not provide a narrative account of the other adverse events.
Why does the design matter for interpretation?
In a randomized comparative study, a treatment effect may be estimated by comparing outcomes between assigned groups, subject to the analysis plan and assumptions. This study is single-group, open-label, and has allocation listed as not applicable. Its primary safety counts are therefore descriptive, not a randomized treatment contrast. Without a concurrent comparator, observed events cannot be separated statistically from events that might have occurred because of the underlying condition, other circumstances, or treatment. The endpoint definition itself also allows AEs that are not judged related to the study drug.
Open-label means that treatment was not masked. The record reports no masked comparator, but does not describe whether event ascertainment used independent review or other procedures to limit assessment bias. Those procedures are not reported in the registry record. The registry also does not report an inferential statistical test, a confidence interval, an adjustment strategy, or a prespecified model for the primary endpoint.
How should uncertainty be understood?
Every observed count is based on the study participants and observation time represented in the record. A confidence interval, in general, expresses the statistical uncertainty around an estimate under a specified method and assumptions. It does not correct limitations such as a small study group, no comparator, or incomplete reporting. A confidence interval for these outcomes is not reported in the registry record. Consequently, the posted counts should be read as observed results, not as precise estimates of event frequency in a broader population.
Time under observation is also relevant to safety interpretation. Participants were followed from informed-consent signature through the end of safety follow-up, up to approximately 40 months, but the registry does not give participant-specific follow-up durations. If observation times differ, a simple participant count does not account for those differences. A time-to-event analysis would use timing and follow-up information, but such an analysis is not reported in the registry record.
What do planning illustrations mean?
Any sample-size calculations accompanying the results are planning illustrations based on the observed effect, not the trial’s own design or an estimate of observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. For non-time-to-event outcomes, the convention is participants per arm. These assumptions describe hypothetical planning comparisons and do not change the fact that this was a single-group study without allocation to two arms. A sample-size illustration is not evidence that a study was powered for the outcome, and it cannot substitute for a reported design rationale or statistical plan. The rationale for the actual enrollment and any prospective power calculation are not reported in the registry record.
General statistical interpretation should distinguish observed data from inference. The observed counts describe the registry’s recorded safety outcomes. Broader claims about causality, comparative risk, or the rate of events beyond this study require information and designs that are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome measure, counting participants with AEs and SAEs, and zero analysis entries. It does not report a multiplicity procedure, such as an approach to controlling false-positive findings across multiple statistical tests. With no analysis entries listed, there is no reported set of inferential tests from which to assess how multiplicity was handled. This should not be interpreted as proof that no analyses were conducted outside the registry record.
The primary safety population is defined as enrolled participants who received at least one partial or total infusion of olipudase alfa in the current study. The record does not report whether all participants were included in every safety summary, how deviations from the planned safety population were handled, or whether any participant was excluded from an outcome analysis.
Missing-data handling is not reported in the registry record. In particular, the record does not describe whether safety information was incomplete for any participant, how incomplete follow-up was treated, or how event status was established when information was unavailable. Participant-specific follow-up duration is also not reported, although the stated safety timeframe extended to the end of follow-up, up to approximately 40 months.
These omissions matter because a participant count can be interpreted only in relation to the population observed and the completeness of outcome ascertainment. The posted counts should not be taken to establish that all possible events were captured or that every participant had identical observation time. The statistical analysis plan, missing-data methods, and any sensitivity analyses are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Olipudase Alfa | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Olipudase Alfa | 0 of 3 |
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 |
|---|---|
| Olipudase Alfa | 3 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Olipudase Alfa |
|---|---|---|
| Tachycardia | Cardiac disorders | 1 of 3 |
| Conjunctivitis Allergic | Eye disorders | 1 of 3 |
| Abdominal Pain | Gastrointestinal disorders | 1 of 3 |
| Diarrhoea | Gastrointestinal disorders | 1 of 3 |
| Pancreatic Cyst | Gastrointestinal disorders | 1 of 3 |
| Pyrexia | General disorders | 1 of 3 |
| Covid-19 | Infections and infestations | 1 of 3 |
| Dermatophytosis | Infections and infestations | 1 of 3 |
| Ear Infection | Infections and infestations | 1 of 3 |
| Gastroenteritis | Infections and infestations | 1 of 3 |
The serious adverse-event count is 0 affected participants among 3 at risk. The other-adverse-event count is 3 affected participants among 3 at risk, and the record reports 0 deaths. These figures count participants with an event in each category, rather than total event episodes. One participant could have experienced more than one event, but episode counts are not reported in the registry record.
An SAE is defined by seriousness criteria, not simply by whether an event occurred. An AE may be serious or not serious, and the broad AE definition includes events whether or not they are considered related to the study drug. Thus, 0 participants recorded with an SAE does not mean that no adverse events occurred: the separate other-adverse-event count is 3 affected participants. Nor does the count alone establish the cause of any event.
The listed serious-event terms are empty. The record does not provide a detailed account of the other adverse events in this summary, nor participant-level timing or duration. These safety results describe the observed counts in an open-label, single-group follow-up and do not provide a comparison with another treatment or a control group.
12. What the Result Does, and Does Not, Mean
The result describes a safety experience observed among participants followed after completing the DFI12712 or LTS13632 study in France. In the registry’s primary outcome, 0 participants were recorded with an SAE, while 3 participants were recorded in the other-adverse-event category. The record reports 0 deaths. These are participant counts during follow-up, not counts of individual event episodes or estimates of comparative treatment effect.
The result does not establish that olipudase alfa caused or prevented any event. The AE definition includes occurrences whether or not they were considered related to study drug, and the registry record does not provide an event-level causality assessment in these posted counts. The study had no comparator group, so the observed outcomes cannot be contrasted with outcomes under another treatment or without treatment. The open-label design also means treatment was not masked.
The findings do not answer whether olipudase alfa improves disease outcomes. The primary endpoint concerns safety and tolerability, not efficacy, and no efficacy result is included in the registry record reported for this study. The results also cannot be generalized automatically to all people with ASMD: participants were specifically those who had completed one of the earlier studies, and the registry reports enrollment of 3 participants.
Precision is limited by the small group and by information not reported in the registry record. A confidence interval, participant-specific follow-up time, and missing-data methods are not reported. As a result, the counts should be read as descriptive observations from this follow-up rather than precise estimates of how often events would occur in a wider population. The record is useful for understanding what was counted in this particular study, but not for making a causal or comparative claim.
13. Why This Trial Matters Statistically
This study illustrates the role of descriptive safety follow-up when participants continue treatment after completing an earlier study. The registry describes a single-group, open-label arrangement intended to evaluate safety and tolerability while providing olipudase alfa until reimbursement became available in France, with a stated fallback duration if reimbursement was not obtained. That context helps explain why the primary outcome focuses on adverse events rather than a randomized comparison.
Statistically, the distinction between participant counts and event counts is important. The posted result tells readers how many participants were recorded with serious and other adverse events, but it does not show how many event episodes occurred or how events were distributed over time. Reporting these counts separately prevents the absence of recorded serious-event participants from being confused with the absence of all adverse events.
The study also demonstrates the limits of inference from small, non-comparative follow-up. A descriptive count can document what occurred in the observed group, but it cannot estimate a relative treatment effect without a comparator. It is also difficult to assess precision without a confidence interval and information about individual follow-up duration. The statistical analysis plan and missing-data methods are not reported in the registry record, so the analysis cannot be evaluated in those respects.
Finally, sample-size planning illustrations should be distinguished from the design that generated the results. The trial itself was single-group; assumptions about equal allocation between two arms refer to hypothetical planning rather than actual assignment. Keeping that distinction clear helps readers avoid treating planning calculations as evidence of observed power or as a comparison that the study conducted.
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 for interpretation is the absence of a comparator. This was an open-label, single-group study, so its safety counts do not provide a randomized comparison with another treatment or a control condition. The record lists enrollment of 3 participants, limiting the amount of observed information available for uncommon outcomes and the precision with which broader event patterns could be characterized.
Participants were selected from those who had completed the DFI12712 or LTS13632 study. The results therefore describe this follow-up population, not an unselected ASMD population. The registry record does not report the characteristics needed to assess how closely participants represent other patients or whether baseline differences could influence the event counts.
The primary outcome is a participant count. The registry does not provide event-level counts, detailed descriptions of other adverse events, participant-specific observation time, or the timing and duration of events. Although the safety period extended from consent to the end of follow-up, up to approximately 40 months, the actual follow-up duration for each participant is not reported in the registry record.
The record does not report a confidence interval, inferential analysis, statistical analysis plan, missing-data approach, or details of event ascertainment and review. It is therefore not possible to assess statistical uncertainty or determine how incomplete observations, if any, were handled. The empty list of serious-event terms does not supply further clinical detail about the other adverse events. These limitations mean the posted results are best understood as a narrow description of recorded participant counts, not as evidence of comparative risk or causality.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate Safety and Tolerability of Olipudase Alfa in Pediatric and Adult Participants With Acid Sphingomyelinase Deficiency (ASMD) Who Completed the DFI12712 or the LTS13632 Study in France — NCT06949358.
- Registry record last updated 2026-04-13; status last verified 2026-03.
- Results first posted 2026-04-13.
- 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 2 study evaluated safety and tolerability of olipudase alfa in pediatric and adult participants with ASMD who had completed the DFI12712 or LTS13632 study in France. It was open-label and single-group, with no comparator; olipudase alfa was given by intravenous infusion every 2 weeks. Enrollment was 3. The registry dates are 2021-11-18 for study start and 2025-04-08 for primary completion.
The primary outcome counted participants with AEs and SAEs from informed-consent signature through the end of safety follow-up, up to approximately 40 months. The posted counts list 0 participants with an SAE, 3 with other adverse events, and 0 deaths. These descriptive counts do not establish causality or comparative safety. The registry record does not report a confidence interval, statistical analysis plan, or missing-data methods.