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 Long Term Safety, Tolerability, and Effectiveness of Olesoxime in Patients With Spinal Muscular Atrophy (SMA) (NCT02628743), a na phase 2 study. The primary outcome is Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02628743 |
| Phase | Phase 2 |
| Condition | Muscular Atrophy, Spinal |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 131 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled participants with spinal muscular atrophy who had previously taken part in one of two earlier olesoxime studies. The safety population is defined as all patients who received at least one dose of study medication. The registry record reports enrollment of 131.
Intervention
The study evaluated olesoxime over the long term. Participants who consented to a dose increase were to receive 10 mg/kg twice daily, orally or through a naso-gastric or gastrostomy tube. The study was open label, so treatment masking was absent.
Comparator
There was no concurrent control group. The study is recorded as single group, with allocation listed as not applicable. It therefore does not provide a like-for-like comparison between olesoxime and placebo or another treatment.
Primary question
The primary outcome is the percentage of participants with adverse events or serious adverse events from baseline up to approximately 3 years. The study purpose also includes long-term tolerability, safety, and effectiveness, but the posted primary outcome is a safety measure.
In plain terms, the registry asks how often adverse events were recorded among participants receiving olesoxime during follow-up. It also lists secondary measures involving motor function, quality of life, and plasma concentrations of olesoxime. Those outcome names indicate what was measured or planned for measurement; they do not, by themselves, show whether scores changed or what those changes were.
Because participants came from earlier studies and there was no concurrent control group, the central question is descriptive: what safety events were reported during this study? A single-arm study can describe events observed during treatment, but it cannot establish how those observations compare with what would have occurred without treatment or under a different treatment. The registry record does not report a comparative effectiveness result.
3. Trial Design
This was a Phase 2, multicenter, open-label, single-arm study of olesoxime in participants with spinal muscular atrophy. The registry record lists Hoffmann-La Roche as the sponsor and enrollment of 131. The study began on 2016-01-20, had primary completion on 2018-12-18, and is recorded as completed.
Participants had previously taken part in one of two studies: an open-label Phase Ib study, or a Phase II/III adaptive, parallel-group, double-blind, randomized, placebo-controlled study. The current study therefore followed participants from earlier research rather than enrolling a population described as treatment-naive. The registry record does not report further details about eligibility criteria or the distribution of participants across the earlier studies.
The intervention was olesoxime. Participants consenting to a dose increase were to receive 10 mg/kg twice daily, by mouth or through a naso-gastric or gastrostomy tube. The record describes administration with breakfast and dinner, preferably at the same time each day. The arm description is incomplete, so further dosing or administration details are not reported in the registry record.
Open-label means the study was not masked: participants and study personnel were not blinded to treatment assignment. A single-arm design means the study had no concurrent comparison group. These features matter when interpreting reported events and any outcome changes, since there is no within-study control group to distinguish changes during follow-up from changes that might occur for other reasons.
The registry lists 21 outcome measures, including the primary safety outcome and secondary measures of motor function, quality of life, and plasma concentrations. It lists no analyses. The statistical plan, including any planned approach to repeated measurements or missing observations, 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.
Overall Study
| Stage | Olesoxime |
|---|---|
| STARTED | 131 |
| COMPLETED | 0 |
| NOT COMPLETED | 131 |
Reasons for not completing this period:
| Reason | Olesoxime |
|---|---|
| Other | 3 |
| Withdrawal by Subject | 50 |
| Study Terminated by Sponsor | 76 |
| Physician Decision | 2 |
Analysis population for the primary outcome, as defined in the registry: Safety population included all patients who received at least one dose of study medication.
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 | Olesoxime |
|---|---|---|
| Participants analysed | 131 | |
| Age, Continuous | years | 14.7 (SD 5.9) |
| Sex: Female, Male: Female | Participants | 66 |
| Sex: Female, Male: Male | Participants | 65 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 3 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 94 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 33 |
| Race/Ethnicity, Customized: Hispanic or Latino | participants | 1 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | participants | 89 |
| Race/Ethnicity, Customized: Not Stated | participants | 29 |
| Race/Ethnicity, Customized: Unknown | participants | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs), measured over Baseline up to approximately 3 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with adverse events or serious adverse events from baseline up to approximately 3 years. It is a binary event outcome at the participant level: a participant either had an event in the defined category during the period or did not. The safety population includes all patients who received at least one dose of study medication.
Safety endpoints are used to describe events occurring during exposure and follow-up. Reporting the proportion of participants with events can make the frequency of recorded events easier to interpret than a list of event counts alone, because a person may experience more than one event. The registry record’s primary endpoint is framed as a percentage of participants, while the posted adverse-event summary also lists participant counts for serious and other adverse events.
The registry reports 36 participants with serious adverse events and 105 with other adverse events, each against a listed at-risk group of 131. It also reports 0 deaths. These entries should be read as separate reported categories; the record does not clarify whether the categories overlap or provide a combined count for the primary endpoint. No overall percentage for the primary endpoint is reported in the registry record.
In general, a safety endpoint describes events recorded during a study; it does not by itself establish that the study drug caused them. That distinction is especially important in an uncontrolled study, where there is no concurrent group to estimate the background frequency of events.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry records an open-label, single-arm study with enrollment of 131. Its primary safety outcome covers adverse events or serious adverse events from baseline up to approximately 3 years. The posted adverse-event summary lists 36 participants with serious adverse events and 105 with other adverse events, with 131 at risk in each listing. It also records 0 deaths. These are descriptive safety figures, not estimates from a comparison between treatment groups.
The listed serious adverse-event terms include pneumonia at 7.6%, lower respiratory tract infection at 3.1%, bronchitis at 2.3%, gastroenteritis at 1.5%, upper respiratory tract infection at 1.5%, and lung infection at 1.5%. These percentages are registry entries for the listed terms. The record does not provide further detail about event counts, timing, duration, severity gradations, or whether individual participants had more than one listed event. It also does not report a causal assessment for these events.
There is no randomized comparator in this study. Thus, the figures describe events observed among participants receiving olesoxime, but cannot establish whether event frequency was higher or lower than it would have been in the absence of olesoxime or under another treatment. A single-arm safety summary can be useful for documenting what was observed, while leaving comparative attribution unresolved.
The study’s stated purpose includes long-term effectiveness, and the registry lists secondary outcomes for motor function and quality of life. However, no outcome analyses are listed. Change estimates, uncertainty intervals, and statistical tests for those measures are not reported in the registry record. Consequently, the registry information does not support an interpretation of improvement, decline, or stability in those outcomes.
Precision also cannot be fully evaluated from the information listed. Confidence intervals are not reported for the primary safety outcome or the serious-event terms. In general, a confidence interval describes a range of values compatible with the data under a specified statistical method; its width conveys precision. Without reported intervals or a stated analysis, readers cannot assess that uncertainty from the registry summary alone.
The record identifies a safety population as patients who received at least one dose. It does not report the number of participants followed for the full period, the extent of missing outcome data, or participant-level exposure time. Those omissions limit interpretation of how complete follow-up was and whether time at risk varied among participants. Overall, the posted results give a descriptive account of reported adverse events, but do not provide a controlled estimate of treatment effect or a reported analysis of effectiveness.
9. Statistical Methods Explained
The registry describes a single-group study, not a randomized comparison. This design determines what statistical conclusions can be drawn. In a randomized controlled study, outcomes can be compared between groups formed by random assignment. Here, there was only an olesoxime group, so the adverse-event summaries describe that group without an internal control for comparison.
What does a percentage of participants with an event represent?
For a binary safety endpoint, each participant is classified according to whether an event in the endpoint definition occurred during the specified period. The percentage of participants with an event is a participant-level summary. It differs from an event count: one participant can have multiple events, while the participant-level percentage counts that person once for the relevant endpoint. The registry’s primary endpoint is defined as the percentage with adverse events or serious adverse events. The posted summary reports participant counts for serious and other adverse events, but does not report the combined primary-endpoint percentage.
The at-risk group is listed as 131 for each of the serious and other adverse-event summaries. The record separately identifies the safety population as patients who received at least one dose. A denominator indicates the population used for a summary; it does not establish that every participant was observed for the same length of time. Follow-up completeness and individual exposure duration are not reported in the registry record.
Why does the single-arm design matter?
Without a concurrent control group, the study cannot estimate a between-group difference in event frequency. This is not merely a matter of choosing a different statistical test: the comparison group needed to estimate that contrast is absent. Events can be described among participants in the study, but the summaries alone cannot separate effects associated with treatment from events related to the underlying condition, other factors, or the passage of time. General statistical interpretation of uncontrolled safety data therefore emphasizes description rather than causal comparison.
What can be said about uncertainty?
A confidence interval is a general statistical tool for expressing uncertainty around an estimate. It gives a range of values compatible with the observed data under the assumptions of the method used. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. No confidence intervals for the primary endpoint or listed adverse-event terms are reported in the registry record. The record also does not report an analysis method for those summaries, so there is no stated interval procedure to assess.
Likewise, a statistical test would require a defined hypothesis and analysis approach. The registry lists no analyses. No p-values or inferential comparisons are reported. The absence of reported tests does not imply that an effect is or is not present; it means that the registry results do not provide a reported inferential analysis for readers to interpret.
How should event terms be read?
The serious adverse-event summary names several event terms and gives a percentage for each. In general, event-term summaries may count participants with a particular type of event, but the registry record does not state the detailed counting rules for these terms. It does not report whether a participant could contribute to more than one term, how recurrent events were handled, or how event terms were coded. The listed percentages should therefore be treated as reported category-specific summaries rather than added together or treated as mutually exclusive shares.
Over-dispersion is a general issue for count data when variability exceeds what a simple model expects. It can affect the uncertainty estimates from count-based analyses. The posted adverse-event information does not provide event-count modeling or a count analysis, so over-dispersion is not something that can be evaluated from the registry summaries. The participant-level safety outcome and the event-term percentages should not be mistaken for a fitted count model.
What does the sample-size information mean?
The registry describes sample-size calculations as planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. Such illustrations are hypothetical planning calculations, not observed trial results and not evidence of the study’s achieved power. The record does not report the trial’s own design justification, and this single-arm study did not have the two-arm allocation described in those planning assumptions.
For time-to-event planning, the registry notes that the illustration gives a total number of events; other planning illustrations give participants per arm. These conventions describe how planning quantities are expressed, not outcomes observed in this trial. No analysis results are listed for the trial itself.
What is not documented?
The registry record does not report the statistical analysis plan, interim analyses, confidence intervals, p-values, or details of adjustment for baseline values or repeated measurements. It also does not report outcome-level analysis populations beyond the safety-population definition for the primary measure. These gaps mean that readers cannot determine how analyses were specified or how uncertainty and incomplete data were handled. The soundest interpretation is to use the posted event summaries descriptively and avoid treating them as adjusted, comparative, or causal estimates.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 21 outcome measures, including the primary safety outcome and secondary measures of motor function, quality of life, and plasma concentrations. When a study examines multiple outcomes, the chance of obtaining an apparently notable result by chance can increase if many statistical tests are conducted. General approaches to multiplicity include prespecifying a primary hypothesis, adjusting significance thresholds, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy, and it lists no analyses. It is therefore not possible to determine whether any adjustment was planned or applied.
Missing data can affect both the estimate and its precision. For example, if outcome availability is related to participants’ health or experience during follow-up, analyses restricted to observed measurements may not represent everyone enrolled. This is a general concern, not a claim about what occurred in this study. The registry record does not report how much outcome data were missing, reasons for missingness, imputation methods, or sensitivity analyses.
The primary safety population is defined as all patients who received at least one dose of study medication. The registry lists 131 at risk for each adverse-event category, but does not report further analysis-population definitions for the secondary outcomes. It also does not report how many participants contributed data at each time point or whether follow-up was complete through approximately 3 years.
These omissions limit assessment of multiplicity, missing-data sensitivity, and the relationship between the stated population and any outcome analysis. Since no analyses are listed, there are no reported estimates or tests whose multiplicity or missing-data handling can be evaluated. The record does not report the statistical plan, so analysis choices should not be inferred from the outcome list alone.
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 |
|---|---|---|---|
| Olesoxime | 36 | 131 | 27.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Olesoxime | 0 of 131 |
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 |
|---|---|
| Olesoxime | 105 of 131 |
Most frequent serious adverse event terms
| Event term | Organ system | Olesoxime |
|---|---|---|
| PNEUMONIA | Infections and infestations | 10 of 131 |
| LOWER RESPIRATORY TRACT INFECTION | Infections and infestations | 4 of 131 |
| BRONCHITIS | Infections and infestations | 3 of 131 |
| GASTROENTERITIS | Infections and infestations | 2 of 131 |
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | 2 of 131 |
| LUNG INFECTION | Infections and infestations | 2 of 131 |
| RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | 2 of 131 |
| FEMUR FRACTURE | Injury, poisoning and procedural complications | 2 of 131 |
| CONSTIPATION | Gastrointestinal disorders | 1 of 131 |
| VOMITING | Gastrointestinal disorders | 1 of 131 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Olesoxime |
|---|---|---|
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | 36 of 131 |
| NASOPHARYNGITIS | Infections and infestations | 30 of 131 |
| PYREXIA | General disorders | 28 of 131 |
| VOMITING | Gastrointestinal disorders | 23 of 131 |
| HEADACHE | Nervous system disorders | 23 of 131 |
| DIARRHOEA | Gastrointestinal disorders | 20 of 131 |
| COUGH | Respiratory, thoracic and mediastinal disorders | 17 of 131 |
| OROPHARYNGEAL PAIN | Respiratory, thoracic and mediastinal disorders | 16 of 131 |
| BRONCHITIS | Infections and infestations | 15 of 131 |
| GASTROENTERITIS | Infections and infestations | 13 of 131 |
Serious events with the highest arm-level rate: pneumonia (7.6%), lower respiratory tract infection (3.1%), bronchitis (2.3%), gastroenteritis (1.5%), upper respiratory tract infection (1.5%).
The serious adverse-event summary lists 36 participants with serious adverse events among 131 at risk. The other adverse-event summary lists 105 participants among 131 at risk. The record also reports 0 deaths. These values are descriptive entries for the olesoxime group; there is no concurrent control group for comparison. The registry does not state whether the serious and other adverse-event categories overlap, so their counts should not be combined.
The listed serious-event terms and percentages are pneumonia, 7.6%; lower respiratory tract infection, 3.1%; bronchitis, 2.3%; gastroenteritis, 1.5%; upper respiratory tract infection, 1.5%; and lung infection, 1.5%. The percentages identify reported term-level summaries. The record does not provide the underlying counts for these terms, clarify whether participants could appear in multiple categories, or report details about timing and recurrence.
In general, an adverse event is an event recorded during a study, and its occurrence during treatment does not on its own establish that treatment caused it. The registry record does not report causal attribution for the listed events. The results are best read as a description of what was recorded in this study, not as a comparison of risks or a causal estimate.
12. What the Result Does, and Does Not, Mean
The posted results document adverse events reported during a long-term, open-label study of olesoxime in participants with spinal muscular atrophy. They list 36 participants with serious adverse events and 105 with other adverse events, each in a group with 131 at risk, as well as 0 deaths. The registry also provides percentages for several serious-event terms. These figures describe the study group; they do not establish how frequently the same events would have occurred in a different group.
The study’s single-arm design is central to interpretation. Without a concurrent comparator, it cannot show whether event frequencies were greater or smaller than under placebo, another treatment, or no study treatment. It also cannot isolate treatment as the cause of any event. The open-label design means masking was absent; the registry does not report whether or how this affected event reporting or assessment.
The study was intended to evaluate long-term tolerability, safety, and effectiveness, and it lists secondary outcomes for motor function, quality of life, and olesoxime concentrations. However, the registry record lists no analyses and provides no results for those secondary measures. No change estimates, uncertainty intervals, or tests are reported for them. The listed outcome names therefore cannot support conclusions about improvement, worsening, or stability.
More generally, a result that is not statistically significant would not by itself demonstrate no effect, and a statistically significant result would not automatically establish a clinically important effect. In this record, there are no reported analyses on which to make either kind of judgment. Nor is there a reported confidence interval to indicate precision.
The defensible conclusion is limited: the registry records safety-event summaries for participants who received olesoxime in this study. It does not provide comparative safety estimates or reported effectiveness analyses. Those limits reflect the design and the information recorded, not proof for or against an effect.
13. Why This Trial Matters Statistically
This study illustrates why design labels matter when interpreting clinical trial statistics. It is recorded as open label and single group, with no randomized comparator. Those features mean its safety summaries answer a descriptive question about events recorded in the study group, rather than a comparative question about differences between treatments. Recognizing that distinction prevents observational event frequencies from being read as causal effects.
The study also has a long-term focus: the primary safety timeframe is baseline up to approximately 3 years, and the stated purpose includes long-term tolerability, safety, and effectiveness. Longer follow-up can make continued observation of safety events relevant, but interpretation also depends on knowing who remained under observation and for how long. The registry record does not report participant-level follow-up duration or completeness, so those aspects cannot be assessed from the posted results.
The registry lists motor-function and quality-of-life outcomes alongside safety and concentration measures. That range of outcomes illustrates the need for clear analysis plans and careful treatment of multiple outcomes. Without reported analyses or a statistical plan, readers cannot determine which secondary findings, if any, were estimated or how multiplicity was handled.
Finally, the record demonstrates the difference between listing an outcome and reporting a result. A measure may appear in a registry without an accompanying estimate, uncertainty interval, or analysis. Here, no analyses are listed, so the available interpretation rests on the reported adverse-event summaries and the documented study design. This distinction is important for researchers using registry results: outcome labels describe measurement aims, while analysis results are needed to assess magnitude and precision.
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 absence of a concurrent control group is the main design limitation for interpreting safety and effectiveness. The study can describe events among participants receiving olesoxime, but cannot provide a like-for-like estimate against another treatment or an untreated group. Open-label conduct also means treatment masking was absent; the registry record does not report any steps used to address possible effects of that design on reporting or assessment.
Participants were selected from people who had taken part in one of two earlier studies. The registry record does not report how many came from each earlier study or provide further detail about their clinical or treatment histories. That limits the ability to characterize the enrolled group beyond the stated condition and prior-study participation.
The arm description is incomplete after the administration instructions. Further details about dosing or treatment implementation are not reported in the registry record. The record also does not provide outcome-level estimates for the listed motor-function and quality-of-life measures, despite stating that long-term effectiveness was among the study’s aims.
The registry lists no analyses and does not report confidence intervals, p-values, detailed statistical methods, missing-data procedures, participant follow-up completeness, or an interim-analysis plan. It does not provide enough information to evaluate the precision of the safety summaries or the handling of repeated outcomes. The serious and other adverse-event summaries are reported separately, but their potential overlap is not clarified. These limitations restrict interpretation to the descriptive safety information that is recorded, without supporting comparative or causal conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate Long Term Safety, Tolerability, and Effectiveness of Olesoxime in Patients With Spinal Muscular Atrophy (SMA) — NCT02628743.
- Registry record last updated 2019-08-09; status last verified 2019-07.
- Results first posted 2019-08-09.
- 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
NCT02628743 is a completed Phase 2, multicenter, open-label, single-arm study of olesoxime in participants with spinal muscular atrophy who had previously participated in one of two earlier studies. The registry lists enrollment of 131 and identifies Hoffmann-La Roche as the sponsor. The study began on 2016-01-20 and had primary completion on 2018-12-18.
The primary outcome is the percentage of participants with adverse events or serious adverse events from baseline up to approximately 3 years. The safety population includes all patients who received at least one dose. The adverse-event summary lists 36 participants with serious adverse events and 105 with other adverse events, each against 131 at risk, and reports 0 deaths. Several serious-event terms and percentages are also listed.
The registry lists secondary outcomes involving motor function, quality of life, and plasma concentrations, but no analyses are listed. The statistical plan, missing-data handling, and comparative effectiveness results are not reported in the registry record. Because the study has no concurrent control group, the posted safety figures are descriptive and do not establish comparative or causal effects.